09 - Scientific and electric apparatus and instruments
16 - Paper, cardboard and goods made from these materials
41 - Education, entertainment, sporting and cultural services
44 - Medical, veterinary, hygienic and cosmetic services; agriculture, horticulture and forestry services
45 - Legal and security services; personal services for individuals.
Goods & Services
Downloadable electronic publications, podcasts and videos in
the field of botulinum toxin. Printed matter, brochures, leaflets, printed teaching
materials in the field of botulinum toxin. Education and training services for healthcare
professionals; arranging and conducting of colloquiums,
conferences, congresses, seminars, symposiums; providing
online publications; providing on-line videos, not
downloadable and production of podcasts. Providing medical information to healthcare professionals,
including information provided via a website. Online social networking services in the field of botulinum
toxin.
The present invention is directed inter alia to a modified botulinum neurotoxin A (BoNT/A) for use in treating cervical dystonia, wherein the modified BoNT/A is administered by intramuscular injection to an affected neck muscle of a subject, wherein the modified BoNT/A is administered by way of a unit dose of greater than 17,000 pg of modified BoNT/A, wherein at least a single unit dose is administered to the affected neck muscle, wherein the total dose administered during the treatment is up to 400,000 pg of modified BoNT/A, and wherein the modified BoNT/A comprises a BoNT/A light-chain and translocation domain, and a BoNT/B receptor binding domain (HC domain). Also provided are corresponding methods, uses, unit dosage forms, and kits.
The present invention is directed to cell-based methods, such as those for determining the clostridial neurotoxin activity of a composition or determining the presence or absence of a clostridial neurotoxin in a composition. The invention is also directed to therapeutic or cosmetic clostridial neurotoxin compositions, methods for producing the same, as well as kits, methods of treatment and uses of the same.
C12Q 1/66 - Measuring or testing processes involving enzymes, nucleic acids or microorganismsCompositions thereforProcesses of preparing such compositions involving luciferase
G01N 33/50 - Chemical analysis of biological material, e.g. blood, urineTesting involving biospecific ligand binding methodsImmunological testing
A method for producing β-trypsin, the method comprising: a) renaturing denatured trypsinogen, thereby producing renatured trypsinogen, wherein the renaturing is carried out in a buffer that comprises L-arginine; b) purifying the renatured trypsinogen by anion exchange chromatography, thereby providing purified renatured trypsinogen; and c) incubating the purified renatured trypsinogen under conditions to promote proteolytic activity of the trypsinogen, wherein trypsinogen is cleaved into β-trypsin by said proteolytic activity; wherein steps a) and b) are carried out under conditions that do not promote the proteolytic activity of trypsinogen; wherein the method does not comprise the addition of a further protease for cleaving trypsinogen into β-trypsin; wherein at least step c) is carried out in a buffer that does not comprise L-arginine; and wherein prior to step c), when present in a buffer that does not comprise L-arginine, the trypsinogen is not subjected to a temperature of >8° C. for more than 38 hours.
The invention relates to stable liquid neurotoxin formulations which are free of animal proteins, comprising a surfactant, an amino acid selected from tryptophan and tyrosine, a buffer comprising sodium, chloride and phosphate ions, which have a pH between 5.5 and 8, and which are stable for 2 months. These compositions are suitable for use in therapy and in particular for administration to a patient to achieve a desired therapeutic or aesthetic effect. The invention also relates to the use of an amino acid selected from tryptophan and tyrosine to protect a proteinaceous neurotoxin from degradation in a liquid composition which is free of animal derived proteins.
The present invention is directed to a modified botulinum neurotoxin A (BoNT/A) for use in treating a facial dystonia, including blepharospasm and hemifacial spasm, wherein the unit dose of the modified BoNT/A is at least 240 pg of modified BoNT/A, wherein the modified BoNT/A is administered by intramuscular injection to an affected muscle of a subject, wherein the total dose administered during the treatment is greater than 24,000 pg and up to 82,500 pg (e.g. up to 75,000 pg) of the modified BoNT/A, and wherein the modified BoNT/A comprises a BoNT/A light-chain and translocation domain (HN), and a BoNT/B receptor binding domain (HC domain).
IMPERIAL COLLEGE INNOVATIONS LIMITED (United Kingdom)
Inventor
Olughu, Williams
Mason, Alison
Polizzi, Karen Marie
Angelova, Ivet
Abstract
The present invention is a biosensor for real-time monitoring of clostridial neurotoxin production during a bacterial fermentation process. The biosensor comprises a surface for performing the analysis of binding events and kinetics, and onto which is immobilised a binding substrate comprising: a donor fluorophore; an acceptor having an absorbance spectrum overlapping the emission spectrum of the donor fluorophore; and a binding region that specifically binds to the clostridial neurotoxin; wherein said binding region being positioned between the donor fluorophore and the acceptor such that, following activation of the donor fluorophore, resonance energy transfer is exhibited between said donor fluorophore and said acceptor.
G01N 33/542 - ImmunoassayBiospecific binding assayMaterials therefor with immune complex formed in liquid phase with steric inhibition or signal modification, e.g. fluorescent quenching
G01N 33/569 - ImmunoassayBiospecific binding assayMaterials therefor for microorganisms, e.g. protozoa, bacteria, viruses
09 - Scientific and electric apparatus and instruments
16 - Paper, cardboard and goods made from these materials
41 - Education, entertainment, sporting and cultural services
44 - Medical, veterinary, hygienic and cosmetic services; agriculture, horticulture and forestry services
45 - Legal and security services; personal services for individuals.
Goods & Services
(1) Downloadable electronic publications, podcasts and videos in the field of botulinum toxin.
(2) Printed matter, brochures, leaflets, printed teaching materials in the field of botulinum toxin. (1) Education and training services for healthcare professionals; arranging and conducting of colloquiums, conferences, congresses, seminars, symposiums; providing online publications; providing on-line videos, not downloadable and production of podcasts.
(2) Providing medical information to healthcare professionals, including information provided via a website.
(3) Online social networking services in the field of botulinum toxin.
45 - Legal and security services; personal services for individuals.
09 - Scientific and electric apparatus and instruments
16 - Paper, cardboard and goods made from these materials
41 - Education, entertainment, sporting and cultural services
44 - Medical, veterinary, hygienic and cosmetic services; agriculture, horticulture and forestry services
Goods & Services
Online social networking services in the field of botulinum toxin. Downloadable electronic publications, podcasts and videos in the field of botulinum toxin. Printed matter, brochures, leaflets, printed teaching materials in the field of botulinum toxin. Education and training services for healthcare professionals; arranging and conducting of colloquiums, conferences, congresses, seminars, symposiums; providing online publications; providing on-line videos, not downloadable and production of podcasts. Providing medical information to healthcare professionals, including information provided via a website.
The present invention is directed to a polypeptide for use in treating pain or an inflammatory disorder, wherein the polypeptide comprises a clostridial neurotoxin light-chain (L-chain), a clostridial neurotoxin translocation domain (HN domain) and/or a clostridial neurotoxin receptor binding domain (HC domain), wherein when the polypeptide comprises a clostridial neurotoxin L-chain, the L-chain is catalytically inactive. Also provided are corresponding methods of treatment and uses.
The present invention is directed to a modified botulinum neurotoxin A (BoNT/A) for use in a method of treating blepharospasm in a subject, wherein the modified BoNT/A is administered by intramuscular injection at a plurality of sites of the face of the subject, the method comprising: a) administering a unit dose of the modified BoNT/A to the lateral upper orbicularis oculi muscle proximal to a first eye of the subject; b) administering a unit dose of the modified BoNT/A to the medial upper orbicularis oculi muscle proximal to the first eye of the subject; and c) administering a unit dose of the modified BoNT/A to the lateral lower orbicularis oculi muscle proximal to the first eye of the subject, wherein the unit dose of the modified BoNT/A is at least 240 pg (preferably 240 pg to 8,000 pg) of modified BoNT/A, wherein the total dose administered during the treatment is up to 24,000 pg of the modified BoNT/A, and wherein the modified BoNT/A comprises a BoNT/A light-chain and translocation domain (HN), and a BoNT/B receptor binding domain (HC domain).
The present invention provides a modified BoNT/A for use in treating facial lines, wherein the modified BoNT/A is administered by intramuscular injection at a plurality of sites of the face of the subject, wherein the modified BoNT/A is administered by way of a unit dose of greater than 1754 pg (e.g. greater than 1800 pg) of modified BoNT/A per site, wherein the plurality of sites are selected from: up to two sites of a corrugator muscle and one site of a procerus muscle for treating glabellar lines, up to five sites of a frontalis muscle for treating forehead lines, and up to three sites of an orbicularis oculi muscle for treating lateral canthal lines, wherein the total dose of modified BoNT/A administered during the treatment is up to 88,000 pg, and wherein the modified BoNT/A comprises a BoNT/A light-chain and translocation domain (HN domain), and a BoNT/B receptor binding domain (HC domain).
09 - Scientific and electric apparatus and instruments
16 - Paper, cardboard and goods made from these materials
41 - Education, entertainment, sporting and cultural services
44 - Medical, veterinary, hygienic and cosmetic services; agriculture, horticulture and forestry services
45 - Legal and security services; personal services for individuals.
Goods & Services
Downloadable electronic publications, podcasts and videos in the field of botulinum toxin. Printed matter, brochures, leaflets, printed teaching materials in the field of botulinum toxin. Education and training services for healthcare professionals; Arranging and conducting of colloquiums, conferences, congresses, seminars, symposiums; Providing online publications; Providing non-downloadable videos and podcasts. Providing medical information to healthcare professionals, including information provided via a website. Online social networking services in the field of botulinum toxin.
Irinotecan phospholipid liposomes with improved storage stability are provided. with related methods of treatment and manufacture. The irinotecan liposomes can have reduced formation of lyso-phosphatidylcholine (lyso-PC) during storage. and prior to administration to a patient.
A61K 31/4745 - QuinolinesIsoquinolines ortho- or peri-condensed with heterocyclic ring systems condensed with ring systems having nitrogen as a ring hetero atom, e.g. phenanthrolines
A61K 9/00 - Medicinal preparations characterised by special physical form
A61K 9/127 - Synthetic bilayered vehicles, e.g. liposomes or liposomes with cholesterol as the only non-phosphatidyl surfactant
A61K 9/1271 - Non-conventional liposomes, e.g. PEGylated liposomes or liposomes coated or grafted with polymers
The present invention is directed to treatment of cervical dystonia using a modified BoNT/A, including a modified botulinum neurotoxin A (BoNT/A) for use in treating cervical dystonia, wherein the modified BoNT/A is administered by intramuscular injection to an affected neck muscle of a subject, wherein the modified BoNT/A is administered by way of a unit dose of 750 pg to 17,000 pg of modified BoNT/A, wherein at least a single unit dose is administered to the affected neck muscle, wherein the total dose administered during the treatment is up to 170,000 pg of modified BoNT/A, and wherein the modified BoNT/A comprises a BoNT/A light-chain and translocation domain, and a BoNT/B receptor binding domain (HC domain). Also provided are associated methods, uses, unit dosage forms, and kits.
The present invention relates to the treatment of autonomic disorders with a clostridial neurotoxin comprising a HCC domain from a BoNT/B, BoNT/D, BoNT/D-C, BoNT/F or BoNT/G, wherein the dose of the clostridial neurotoxin to be administered to the patient is equivalent to or lower than the dose of BoNT/A that would be used to treat the same autonomic disorder.
The present invention provides a clostridial neurotoxin for use in a method of suppressing visceral pain in a patient. The method comprises: (a) identifying an organ in the patient that is causing said visceral pain; (b) mapping said organ to a specific dermatome nerve according to the following instructions, thereby matching said organ to one or more specifically designated dermatome nerve(s): urinary bladder maps to the T11, T12, L1, S1, S2, S3 and/or S4 dermatome nerve(s); fallopian tube(s) maps to the T11 dermatome nerve(s); uterus maps to the T12 and/or L1 dermatome nerve(s); cervix maps to the S2, S3 10 and/or S4 dermatome nerve(s); stomach maps to the T8, T9 and/or T10 dermatome nerve(s); liver maps to the T8, T9, T10 and/or T11 dermatome nerve(s); gall bladder maps to the T8, T9, T10 and/or T11 dermatome nerve(s); pancreas maps to the T7, T8, T9, T10, T11 and/or T12 dermatome nerve(s); small intestine maps to the T10, T11 and/or T12 dermatome nerve(s); colon maps to the T11, S1, S2, S3 and/or S4 dermatome nerve(s); kidney maps to the T10, T11, T12 and/or L1 dermatome nerve(s); ureter maps to the T11, T12 and/or L1 dermatome nerve(s); ovary maps to the T11 dermatome nerve(s); testes maps to the T10, T11, L1, L2, S1, S2, S3 and/or S4 dermatome nerve(s); epididymis maps to the T10, T11, L1, L2, S1, S2, S3 and/or S4 dermatome nerve(s); and (c) administering a therapeutically effective amount of a clostridial neurotoxin at a site proximal to said one or more specifically designated dermatome nerve(s), wherein following administration of said clostridial neurotoxin to the patient, the clostridial neurotoxin is transported via retrograde axonal transport to the spinal cord where it binds sensory afferent nerve cells, enters said cells by receptor-mediated endocytosis and suppresses neurotransmitter release therefrom, thereby suppressing said visceral pain.
The present invention is directed to a polypeptide for use in treating pain or an inflammatory disorder, wherein the polypeptide comprises a clostridial neurotoxin light-chain (L-chain), a clostridial neurotoxin translocation domain (HN domain) and/or a clostridial neurotoxin receptor binding domain (Hc domain), wherein when the polypeptide comprises a clostridial neurotoxin L-chain, the L-chain is catalytically inactive. Also provided are corresponding methods of treatment and uses.
42 - Scientific, technological and industrial services, research and design
44 - Medical, veterinary, hygienic and cosmetic services; agriculture, horticulture and forestry services
Goods & Services
Retail pharmacy services; online retail store services featuring pharmaceutical products; online retail pharmacy services for the ordering, purchase, and delivery of pharmaceutical products; pharmaceutical services, namely, processing prescription orders Platform as a service (PAAS) featuring computer software for permitting users to identify, request and receive pharmaceutical products Providing information relating to therapeutic properties of pharmaceuticals
41.
TREATMENT OF A HEADACHE DISORDER WITH A BOTULINUM NEUROTOXIN A
Combination therapy regimens including liposomal irinotecan, oxaliplatin and 5-fluorouracil are useful in the treatment of pancreatic cancer, including treatment of patients diagnosed with previously untreated metastatic adenocarcinoma of the pancreas. The combination therapy can include the administration of liposomal irinotecan, oxaliplatin, leucovorin and 5-fluorouracil once every two weeks.
A61K 31/436 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a six-membered ring having oxygen as a ring hetero atom, e.g. rapamycin
A61K 31/4745 - QuinolinesIsoquinolines ortho- or peri-condensed with heterocyclic ring systems condensed with ring systems having nitrogen as a ring hetero atom, e.g. phenanthrolines
A61K 31/475 - QuinolinesIsoquinolines having an indole ring, e.g. yohimbine, reserpine, strychnine, vinblastine
A61K 31/513 - PyrimidinesHydrogenated pyrimidines, e.g. trimethoprim having oxo groups directly attached to the heterocyclic ring, e.g. cytosine
A61K 47/20 - Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing sulfur, e.g. dimethyl sulfoxide [DMSO], docusate, sodium lauryl sulfate or aminosulfonic acids
43.
Methods For Treating Pancreatic Cancer Using Combination Therapies
Provided are methods for treating pancreatic cancer in a patient by administering liposomal irinotecan (MM-398) alone or in combination with additional therapeutic agents. In one embodiment, the liposomal irinotecan (MM-398) is co-administered with 5-fluorouracil and leucovorin.
A61K 31/4745 - QuinolinesIsoquinolines ortho- or peri-condensed with heterocyclic ring systems condensed with ring systems having nitrogen as a ring hetero atom, e.g. phenanthrolines
A61K 9/00 - Medicinal preparations characterised by special physical form
A61K 9/127 - Synthetic bilayered vehicles, e.g. liposomes or liposomes with cholesterol as the only non-phosphatidyl surfactant
A61K 31/513 - PyrimidinesHydrogenated pyrimidines, e.g. trimethoprim having oxo groups directly attached to the heterocyclic ring, e.g. cytosine
A61K 31/519 - PyrimidinesHydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
A61K 47/24 - Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing atoms other than carbon, hydrogen, oxygen, halogen, nitrogen or sulfur, e.g. cyclomethicone or phospholipids
A61K 47/26 - Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharidesDerivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
A61K 47/28 - Steroids, e.g. cholesterol, bile acids or glycyrrhetinic acid
The present invention is directed to a modified clostridial neurotoxin comprising a botulinum neurotoxin A (BoNT/A) Hcc domain, wherein the Hcc domain comprises a modification of methionine 1144 (MI 144), and wherein the modification increases oxidative resistance of the modified clostridial neurotoxin when compared to an otherwise identical clostridial neurotoxin lacking the modification. Also provided are (inter alia) corresponding methods for producing the same, methods for selecting oxidation resistant clostridial neurotoxins, nucleic acids encoding the same, and therapeutic uses of said modified clostridial neurotoxins.
42 - Scientific, technological and industrial services, research and design
Goods & Services
Research and development in the pharmaceutical and biotechnology fields; providing medical and scientific research information in the field of pharmaceuticals and clinical trials; conducting clinical trials for pharmaceutical products for others
Provided are methods for treating pancreatic cancer in a patient by administering liposomal irinotecan (MM-398) alone or in combination with additional therapeutic agents. In one embodiment, the liposomal irinotecan (MM-398) is co-administered with 5-fluorouracil and leucovorin.
A61K 31/4745 - QuinolinesIsoquinolines ortho- or peri-condensed with heterocyclic ring systems condensed with ring systems having nitrogen as a ring hetero atom, e.g. phenanthrolines
A61K 9/00 - Medicinal preparations characterised by special physical form
A61K 9/127 - Synthetic bilayered vehicles, e.g. liposomes or liposomes with cholesterol as the only non-phosphatidyl surfactant
A61K 31/513 - PyrimidinesHydrogenated pyrimidines, e.g. trimethoprim having oxo groups directly attached to the heterocyclic ring, e.g. cytosine
A61K 31/517 - PyrimidinesHydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with carbocyclic ring systems, e.g. quinazoline, perimidine
A61K 31/519 - PyrimidinesHydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
A61K 31/573 - Compounds containing cyclopenta[a]hydrophenanthrene ring systemsDerivatives thereof, e.g. steroids substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane or progesterone substituted in position 21, e.g. cortisone, dexamethasone, prednisone or aldosterone
A61K 45/06 - Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
48.
İXCELLENCE NETWORK Centers of excellence for HCP education
09 - Scientific and electric apparatus and instruments
16 - Paper, cardboard and goods made from these materials
41 - Education, entertainment, sporting and cultural services
44 - Medical, veterinary, hygienic and cosmetic services; agriculture, horticulture and forestry services
45 - Legal and security services; personal services for individuals.
Goods & Services
Downloadable electronic publications, podcasts and videos in
the field of botulinum toxin. Printed matter, brochures, leaflets, printed teaching
materials in the field of botulinum toxin. Education and training services for healthcare
professionals; arranging and conducting of colloquiums,
conferences, congresses, seminars, symposiums; providing
online publications; providing non-downloadable on-line
videos and production of podcasts. Providing medical information to healthcare professionals,
including information provided via a website. Online social networking services in the field of botulinum
toxin.
49.
Clostridial Neurotoxins Comprising an Exogenous Activation Loop
The present invention relates to a method for proteolytically processing a single-chain clostridial neurotoxin into a corresponding di-chain clostridial neurotoxin, the method comprising: providing a single-chain clostridial neurotoxin; and contacting the single-chain clostridial neurotoxin with furin; wherein the single-chain clostridial neurotoxin has an activation loop comprising or consisting of the polypeptide sequence Arg-Xaa-Xaa-Arg; and wherein furin hydrolyses a peptide bond of the activation loop thereby producing a di-chain clostridial neurotoxin. The invention also relates to engineered clostridial neurotoxins and methods for manufacturing the same, as well as related pharmaceutical compositions, nucleotide sequences, and therapeutic and cosmetic uses.
The present invention relates to clostridial neurotoxins engineered to comprise an endosomal protease cleavage site within the activation loop, wherein cleavage at said site produces an active di-chain clostridial neurotoxin. The invention also relates to methods for manufacturing the same, as well as related pharmaceutical compositions, nucleotide sequences, and therapeutic and cosmetic uses. The invention further relates to a method for proteolytically processing said single-chain clostridial neurotoxins into a corresponding di- chain clostridial neurotoxin.
The present invention relates to clostridial neurotoxins engineered to comprise an exogenous protease cleavage site within a modified activation loop, wherein cleavage at said site produces an active di-chain clostridial neurotoxin. The invention also relates to methods for manufacturing the same, as well as related pharmaceutical compositions, nucleotide 10 sequences, and therapeutic and cosmetic uses. The invention further relates to a method for proteolytically processing said single-chain clostridial neurotoxins into a corresponding di- chain clostridial neurotoxin.
The present invention provides a method of treating a patient suffering from bladder pain syndrome, said method comprising administering a solution containing a clostridial neurotoxin into the bladder of the patient; increasing the volume of solution comprising the clostridial neurotoxin present within the bladder, thereby applying a mechanical force against the inner surface of the urothelial layer; and maintaining said volume of solution comprising the clostridial neurotoxin present within the bladder at a volume that does not give rise to patient micturition and for a duration of at least 30 minutes, thereby allowing the clostridial neurotoxin to diffuse across the urothelial layer and into the lamina propria, where the clostridial neurotoxin binds to primary sensory afferent nerve fibres, suppresses secretion of neurotransmitters therefrom, and alleviates bladder pain.
The present invention is directed to cell-free methods, such as those for determining the clostridial neurotoxin activity of a composition, determining whether or not a composition comprises clostridial neurotoxin polypeptides, and/or determining whether or not clostridial neurotoxin polypeptides or portions thereof comprised in a composition comprise an activity-altering property. The invention is also directed to an isolated capture substrate for a clostridial neurotoxin, use of the same, therapeutic or cosmetic clostridial neurotoxin compositions, and methods for producing the same.
C12Q 1/37 - Measuring or testing processes involving enzymes, nucleic acids or microorganismsCompositions thereforProcesses of preparing such compositions involving hydrolase involving peptidase or proteinase
G01N 33/569 - ImmunoassayBiospecific binding assayMaterials therefor for microorganisms, e.g. protozoa, bacteria, viruses
The present invention provides a clostridial neurotoxin for use in a method of treating a brain disorder in a patient by promoting a neuroimmune response.
The invention relates to stable liquid neurotoxin formulations which are free of animal proteins, comprising a surfactant, an amino acid selected from tryptophan and tyrosine, a buffer comprising sodium, chloride and phosphate ions, which have a pH between 5.5 and 8, and which are stable for 2 months. These compositions are suitable for use in therapy and in particular for administration to a patient to achieve a desired therapeutic or aesthetic effect. The invention also relates to the use of an amino acid selected from tryptophan and tyrosine to protect a proteinaceous neurotoxin from degradation in a liquid composition which is free of animal derived proteins.
09 - Scientific and electric apparatus and instruments
16 - Paper, cardboard and goods made from these materials
41 - Education, entertainment, sporting and cultural services
44 - Medical, veterinary, hygienic and cosmetic services; agriculture, horticulture and forestry services
45 - Legal and security services; personal services for individuals.
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(1) Downloadable electronic publications in the nature of podcasts in the field of botulinum toxin; Downloadable electronic publications namely downloadable digital content being videos in the filed of botulinum toxin.
(2) Printed matter, namely, brochures, leaflets, printed teaching materials in the field of botulinum toxin. (1) Education and training of healthcare professionals in the field of botulinum toxin; arranging and conducting of colloquiums, conferences, congresses, seminars, symposiums in the field of botulinum toxin; providing online publications of brochures, leaflets, printed teaching materials in the field of botulinum toxin; providing non-downloadable on-line videos in the field of botulinum toxin and; production of podcasts.
(2) Providing medical information in the field of botulinum toxin to healthcare professionals, via a website.
(3) Online social networking services in the field of botulinum toxin.
57.
IXCELLENCE NETWORK CENTERS OF EXCELLENCE FOR HCP EDUCATION
09 - Scientific and electric apparatus and instruments
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45 - Legal and security services; personal services for individuals.
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Downloadable electronic publications in the nature of podcasts in the field of botulinum toxin Printed matter, namely, hand-outs, brochures, and printed teaching materials all in the field of botulinum toxin Education and training services for healthcare professionals, namely, conducting providing live and on-line classes, colloquiums, conferences, congresses, seminars, symposiums and workshops in the field of botulinum toxin; arranging and conducting of colloquiums, conferences, congresses, seminars, symposiums in the field of botulinum toxin; providing online non-downloadable publications in the nature of podcasts, articles and brochures in the field of botulinum toxin Providing medical information to healthcare professionals, including medical information provided via a website Online social networking services in the field of botulinum toxin.
The present invention relates to the treatment of skin conditions with neurotoxins, and non-therapeutic uses for cosmetic treatment of the skin. Administration of the neurotoxin induces secretion of one or more sebaceous lipid(s) selected from a squalene, a fatty acid, a cholesterol, and a wax ester to an epidermal layer of skin.
09 - Scientific and electric apparatus and instruments
16 - Paper, cardboard and goods made from these materials
41 - Education, entertainment, sporting and cultural services
44 - Medical, veterinary, hygienic and cosmetic services; agriculture, horticulture and forestry services
45 - Legal and security services; personal services for individuals.
Goods & Services
Downloadable electronic publications, podcasts and videos in the field of botulinum toxin. Printed matter, brochures, leaflets, printed teaching materials in the field of botulinum toxin. Education and training services for healthcare professionals; Arranging and conducting of colloquiums, conferences, congresses, seminars, symposiums; Providing online publications; Providing nondownloadable videos and podcasts. Providing medical information to healthcare professionals, including information provided via a website. Online social networking services in the field of botulinum toxin.
The present invention relates to a modified BoNT/A for use in treating facial lines, wherein the modified BoNT/A is administered by intramuscular injection at a plurality of sites of the face of the subject, wherein the modified BoNT/A is administered by way of a unit dose of Units to 41 Units of modified BoNT/A per site and wherein 1 Unit is an amount of the modified BoNT/A that corresponds to the calculated median lethal dose (LD50) in mice, wherein the plurality of sites are selected from: up to two sites of a corrugator muscle and one site of a procerus muscle for treating glabellar lines, up to five sites of a frontalis muscle for treating forehead lines; and up to three sites at the external part of an orbicularis oculi muscle for treating lateral canthal lines, wherein the total dose of modified BoNT/A administered during the treatment is up to 574 Units, and wherein the modified BoNT/A comprises a modification at one or more amino acid residue(s) selected from: ASN 886, ASN 905, GLN 915, ASN 918, GLU 920, ASN 930, ASN 954, SER 955, GLN 991, GLU 992, GLN 995, ASN 1006, ASN 1025, ASN 1026, ASN 1032, ASN 1043, ASN 1046, ASN 1052, ASP 15 1058, HIS 1064, ASN 1080, GLU 1081, GLU 1083, ASP 1086, ASN 1188, ASP 1213, GLY 1215, ASN 1216, GLN 1229, ASN 1242, ASN 1243, SER 1274, and THR 1277, wherein the modification is selected from: i. substitution of an acidic surface exposed amino acid residue with a basic amino acid residue; ii. substitution of an acidic surface exposed amino acid residue with an uncharged amino acid residue; iii. substitution of an uncharged surface exposed amino acid residue with a basic amino acid residue; iv. insertion of a basic amino acid residue; and v. deletion of an acidic surface exposed amino acid residue. Also provided are corresponding methods of treatment and uses, as well as unit dosage forms, and kits.
The present invention is directed inter alia to a modified botulinum neurotoxin A (BoNT/A) for use in treating cervical dystonia, wherein the modified BoNT/A is administered by intramuscular injection to an affected neck muscle of a subject, wherein the modified BoNT/A is administered by way of a unit dose of greater than 17,000 pg of modified BoNT/A, wherein at least a single unit dose is administered to the affected neck muscle, wherein the total dose administered during the treatment is up to 400,000 pg of modified BoNT/A, and wherein the modified BoNT/A comprises a BoNT/A light-chain and translocation domain, and a BoNT/B receptor binding domain (HC domain). Also provided are corresponding methods, uses, unit dosage forms, and kits.
The present invention is directed to a modified botulinum neurotoxin A (BoNT/A) for use in treating a facial dystonia, including blepharospasm and hemifacial spasm, wherein the unit dose of the modified BoNT/A is at least 240 pg of modified BoNT/A, wherein the modified BoNT/A is administered by intramuscular injection to an affected muscle of a subject, wherein the total dose administered during the treatment is greater than 24,000 pg and up to 82,500 pg (e.g. up to 75,000 pg) of the modified BoNT/A, and wherein the modified BoNT/A comprises a BoNT/A light-chain and translocation domain (HN), and a BoNT/B receptor binding domain (HC domain).
The invention is directed to treatment of limb spasticity using a modified botulinum neurotoxin A (BoNT/A) comprising a BoNT/A light-chain and translocation domain, and a BoNT/B receptor binding domain (HC domain). Also provided are unit dosage forms of said modified BoNT/A and corresponding kits.
09 - Scientific and electric apparatus and instruments
16 - Paper, cardboard and goods made from these materials
41 - Education, entertainment, sporting and cultural services
44 - Medical, veterinary, hygienic and cosmetic services; agriculture, horticulture and forestry services
45 - Legal and security services; personal services for individuals.
Goods & Services
Downloadable electronic publications in the field of
botulinum toxin. Printed matter, brochures, printed teaching materials in the
field of botulinum toxin. Education and training services for healthcare
professionals; arranging and conducting of colloquiums,
conferences, congresses, seminars, symposiums; providing
online publications. Providing medical information to healthcare professionals,
including information provided via a website. Online social networking services in the field of botulinum
toxin.
The present invention provides a modified botulinum neurotoxin A (BoNT/A) L-chain protease that demonstrates enhanced cleaveage of human SNAP-23 (hSNAP-23) relative to unmodified (wild-type) BoNT/A L-chain protease, together with the use thereof for cleaving hSNAP-23.
09 - Scientific and electric apparatus and instruments
16 - Paper, cardboard and goods made from these materials
41 - Education, entertainment, sporting and cultural services
44 - Medical, veterinary, hygienic and cosmetic services; agriculture, horticulture and forestry services
45 - Legal and security services; personal services for individuals.
Goods & Services
(1) Downloadable electronic publications in the nature of podcasts in the field of botulinum toxin; Downloadable electronic publications namely downloadable digital content being videos in the filed of botulinum toxin.
(2) Printed matter, namely, brochures, leaflets, printed teaching materials in the field of botulinum toxin. (1) Education and training of healthcare professionals in the field of botulinum toxin; arranging and conducting of colloquiums, conferences, congresses, seminars, symposiums in the field of botulinum toxin; providing online publications of brochures, leaflets, printed teaching materials in the field of botulinum toxin; providing non-downloadable on-line videos in the field of botulinum toxin; production of podcasts.
(2) Providing medical information in the field of botulinum toxin to healthcare professionals, via a website.
(3) Online social networking services in the field of botulinum toxin.
68.
IXCELLENCE SHARING EXPERTISE, IMPROVING PATIENT CARE
09 - Scientific and electric apparatus and instruments
16 - Paper, cardboard and goods made from these materials
41 - Education, entertainment, sporting and cultural services
44 - Medical, veterinary, hygienic and cosmetic services; agriculture, horticulture and forestry services
45 - Legal and security services; personal services for individuals.
Goods & Services
Downloadable electronic publications in the nature of podcasts and audio files in the field of botulinum toxin Printed matter, namely, hand-outs, brochures, and printed teaching materials all in the field of botulinum toxin Education and training services for healthcare professionals, namely, conducting and providing live and on-line classes, colloquiums, conferences, congresses, seminars, symposiums and workshops in the field of botulinum toxin; arranging and conducting of colloquiums, conferences, congresses, seminars, symposiums in the field of botulinum toxin; providing online non-downloadable publications in the nature of podcasts, audio files, articles and brochures in the field of botulinum toxin Providing medical information to healthcare professionals, including medical information provided via a website Online social networking services in the field of botulinum toxin
69.
İXCELLENCE Sharing expertise, improving patient care
09 - Scientific and electric apparatus and instruments
16 - Paper, cardboard and goods made from these materials
41 - Education, entertainment, sporting and cultural services
44 - Medical, veterinary, hygienic and cosmetic services; agriculture, horticulture and forestry services
45 - Legal and security services; personal services for individuals.
Goods & Services
Downloadable electronic publications in the field of botulinum toxin. Printed matter, brochures, printed teaching materials in the field of botulinum toxin. Education and training services for healthcare professionals; Arranging and conducting of colloquiums, conferences, congresses, seminars, symposiums; Providing online publications. Providing medical information to healthcare professionals, including information provided via a website. Online social networking services in the field of botulinum toxin.
The present invention relates to a modified botulinum neurotoxin A (BoNT/A) for use in treating limb spasticity or paediatric limb spasticity, wherein the modified BoNT/A is administered by intramuscular injection to a plurality of affected muscles of a subject, wherein the modified BoNT/A is administered by way of a unit dose of 53 Units to 948 Units or 26.5 Units to 474 Units of modified BoNT/A at the plurality of affected muscles.
There is provided a method of controlling operation of a fed batch process in a bioreactor vessel, comprising transitioning from a batch phase to a production phase in dependence on a relationship between an oxygen supply parameter O and a dissolved oxygen value DO.
The present invention relates to a clostridial neurotoxin for use in treating post-operative surgical pain in a patient, said method comprising administering to a patient a clostridial neurotoxin more than 5 days prior to surgery and wherein the clostridial neurotoxin is administered: i) intradermally; or ii) intrathecally.
The present invention relates to a clostridial neurotoxin for use in treating post-operative surgical pain in a patient, said method comprising administering to a patient a clostridial neurotoxin more than 5 days prior to surgery and wherein the clostridial neurotoxin is administered: i) intradermally; or ii) intrathecally.
Also provided are corresponding methods of treatment and administration dosages of a clostridial neurotoxin.
The present invention provides liposome compositions containing substituted ammonium and/or polyanion, and optionally with a desired therapeutic or imaging entity. The present invention also provide methods of making the liposome compositions provided by the present invention.
A61K 31/4745 - QuinolinesIsoquinolines ortho- or peri-condensed with heterocyclic ring systems condensed with ring systems having nitrogen as a ring hetero atom, e.g. phenanthrolines
A61K 47/60 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additivesTargeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyureas or polyurethanes the organic macromolecular compound being a polyoxyalkylene oligomer, polymer or dendrimer, e.g. PEG, PPG, PEO or polyglycerol
A61K 47/69 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additivesTargeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit
A61K 9/00 - Medicinal preparations characterised by special physical form
A61K 9/127 - Synthetic bilayered vehicles, e.g. liposomes or liposomes with cholesterol as the only non-phosphatidyl surfactant
A61K 31/475 - QuinolinesIsoquinolines having an indole ring, e.g. yohimbine, reserpine, strychnine, vinblastine
A61K 31/704 - Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages attached to a carbocyclic compound, e.g. phloridzin attached to a condensed carbocyclic ring system, e.g. sennosides, thiocolchicosides, escin, daunorubicin, digitoxin
A61K 31/337 - Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having four-membered rings, e.g. taxol
A61K 31/4375 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a six-membered ring having nitrogen as a ring hetero atom, e.g. quinolizines, naphthyridines, berberine, vincamine
A61K 47/26 - Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharidesDerivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
A61K 47/24 - Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing atoms other than carbon, hydrogen, oxygen, halogen, nitrogen or sulfur, e.g. cyclomethicone or phospholipids
A61K 47/28 - Steroids, e.g. cholesterol, bile acids or glycyrrhetinic acid
The present invention provides a clostridial neurotoxin for use in a method of suppressing visceral pain in a patient. The method comprises: (a) identifying an organ in the patient that is causing said visceral pain; (b) mapping said organ to a specific dermatome nerve according to the following instructions, thereby matching said organ to one or more specifically designated dermatome nerve(s): urinary bladder maps to the T11, T12, L1, S1, S2, S3 and/ or S4 dermatome nerve(s); fallopian tube(s) maps to the T11 dermatome nerve(s); uterus maps to the T12 and/ or L1 dermatome nerve(s); cervix maps to the S2, S3 10 and/ or S4 dermatome nerve(s); stomach maps to the T8, T9 and/ or T10 dermatome nerve(s); liver maps to the T8, T9, T10 and/ or T11 dermatome nerve(s); gall bladder maps to the T8, T9, T10 and/ or T11 dermatome nerve(s); pancreas maps to the T7, T8, T9, T10, T11 and/ or T12 dermatome nerve(s); small intestine maps to the T10, T11 and/ or T12 dermatome nerve(s); colon maps to the T11, S1, S2, S3 and/ or S4 dermatome nerve(s);kidney maps to the T10, T11, T12 and/ or L1 dermatome nerve(s); ureter maps to the T11, T12 and/ or L1 dermatome nerve(s); ovary maps to the T11 dermatome nerve(s); testes maps to the T10, T11, L1, L2, S1, S2, S3 and/ or S4 dermatome nerve(s); epididymis maps to the T10, T11, L1, L2, S1, S2, S3 and/ or S4 dermatome nerve(s); and (c) administering a therapeutically effective amount of a clostridial neurotoxin at a site proximal to said one or more specifically designated dermatome nerve(s), wherein following administration of said clostridial neurotoxin to the patient, the clostridial neurotoxin is transported via retrograde axonal transport to the spinal cord where it binds sensory afferent nerve cells, enters said cells by receptor-mediated endocytosis and suppresses neurotransmitter release therefrom, thereby suppressing said visceral pain.
A61K 38/48 - Hydrolases (3) acting on peptide bonds (3.4)
A61P 1/00 - Drugs for disorders of the alimentary tract or the digestive system
A61P 1/16 - Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
A61P 1/18 - Drugs for disorders of the alimentary tract or the digestive system for pancreatic disorders, e.g. pancreatic enzymes
A61P 13/02 - Drugs for disorders of the urinary system of urine or of the urinary tract, e.g. urine acidifiers
A61P 13/10 - Drugs for disorders of the urinary system of the bladder
A61P 13/12 - Drugs for disorders of the urinary system of the kidneys
A61P 15/00 - Drugs for genital or sexual disordersContraceptives
A61P 25/02 - Drugs for disorders of the nervous system for peripheral neuropathies
A61P 25/04 - Centrally acting analgesics, e.g. opioids
A61P 29/00 - Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agentsNon-steroidal antiinflammatory drugs [NSAID]
Irinotecan phospholipid liposomes with improved storage stability are provided, with related methods of treatment and manufacture. The irinotecan liposomes can have reduced formation of lyso-phosphatidylcholine (lyso-PC) during storage, and prior to administration to a patient.
A61K 31/4745 - QuinolinesIsoquinolines ortho- or peri-condensed with heterocyclic ring systems condensed with ring systems having nitrogen as a ring hetero atom, e.g. phenanthrolines
The present invention is directed to a modified botulinum neurotoxin A (BoNT/A) for use in a method of treating blepharospasm in a subject, wherein the modified BoNT/A is administered by intramuscular injection at a plurality of sites of the face of the subject, the method comprising: a) administering a unit dose of the modified BoNT/A to the lateral upper orbicularis oculi muscle proximal to a first eye of the subject; b) administering a unit dose of the modified BoNT/A to the medial upper orbicularis oculi muscle proximal to the first eye of the subject; and c) administering a unit dose of the modified BoNT/A to the lateral lower orbicularis oculi muscle proximal to the first eye of the subject, wherein the unit dose of the modified BoNT/A is at least 240 pg (preferably 240 pg to 8,000 pg) of modified BoNT/A, wherein the total dose administered during the treatment is up to 24,000 pg of the modified BoNT/A, and wherein the modified BoNT/A comprises a BoNT/A light-chain and translocation domain (HN), and a BoNT/B receptor binding domain (HC domain).
Provided are methods for treating pancreatic cancer in a patient by administering liposomal irinotecan (MM-398) alone or in combination with additional therapeutic agents. In one embodiment, the liposomal irinotecan (MM-398) is co-administered with 5-fluorouracil and leucovorin.
A61K 31/4745 - QuinolinesIsoquinolines ortho- or peri-condensed with heterocyclic ring systems condensed with ring systems having nitrogen as a ring hetero atom, e.g. phenanthrolines
A61K 9/00 - Medicinal preparations characterised by special physical form
A61K 9/127 - Synthetic bilayered vehicles, e.g. liposomes or liposomes with cholesterol as the only non-phosphatidyl surfactant
A61K 9/1271 - Non-conventional liposomes, e.g. PEGylated liposomes or liposomes coated or grafted with polymers
A61K 31/513 - PyrimidinesHydrogenated pyrimidines, e.g. trimethoprim having oxo groups directly attached to the heterocyclic ring, e.g. cytosine
A61K 31/519 - PyrimidinesHydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
A61K 47/24 - Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing atoms other than carbon, hydrogen, oxygen, halogen, nitrogen or sulfur, e.g. cyclomethicone or phospholipids
A61K 47/26 - Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharidesDerivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
A61K 47/28 - Steroids, e.g. cholesterol, bile acids or glycyrrhetinic acid
80.
MODIFIED BONT/A FOR USE IN THE TREATMENT OF CERVICAL DYSTONIA
Combination therapies for treating cancer comprising administration of a topoisomerase-1 inhibitor and a PARP inhibitor are provided. The topoisomerase-1 inhibitor can be delivered as a liposomal formulation that provides for prolonged accumulation of the topoisomerase-1 inhibitor within a tumor relative to outside of the tumor. Therapeutic benefit can thereby be obtained by delaying the administration of the PARP inhibitor after each administration of a liposomal irinotecan formulation until the accumulation of the topoisomerase inhibitor in the tumor is sufficiently greater than outside the tumor to result in increased efficacy of the PARP inhibitor and topoisomerase inhibitor within the tumor, while reducing the peripheral toxicity of the combination therapy. The therapies disclosed herein are useful in the treatment of human cancers with solid tumors, including cervical cancer.
A61K 31/436 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a six-membered ring having oxygen as a ring hetero atom, e.g. rapamycin
A61K 31/4745 - QuinolinesIsoquinolines ortho- or peri-condensed with heterocyclic ring systems condensed with ring systems having nitrogen as a ring hetero atom, e.g. phenanthrolines
A61K 31/166 - Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide having the carbon atom of a carboxamide group directly attached to the aromatic ring, e.g. procainamide, procarbazine, metoclopramide, labetalol
A61K 31/416 - 1,2-Diazoles condensed with carbocyclic ring systems, e.g. indazole
A61K 31/4184 - 1,3-Diazoles condensed with carbocyclic rings, e.g. benzimidazoles
A61K 31/475 - QuinolinesIsoquinolines having an indole ring, e.g. yohimbine, reserpine, strychnine, vinblastine
A61K 31/502 - PyridazinesHydrogenated pyridazines ortho- or peri-condensed with carbocyclic ring systems, e.g. cinnoline, phthalazine
A61K 31/55 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole
A61K 9/127 - Synthetic bilayered vehicles, e.g. liposomes or liposomes with cholesterol as the only non-phosphatidyl surfactant
A61K 47/20 - Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing sulfur, e.g. dimethyl sulfoxide [DMSO], docusate, sodium lauryl sulfate or aminosulfonic acids
A61K 47/06 - Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
A61K 9/00 - Medicinal preparations characterised by special physical form
A61K 31/454 - Non-condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. pimozide, domperidone
A61K 31/5025 - PyridazinesHydrogenated pyridazines ortho- or peri-condensed with heterocyclic ring systems
A61K 45/06 - Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
82.
Methods for Treating Metastatic Pancreatic Cancer Using Combination Therapies Comprising Liposomal Irinotecan and Oxaliplatin
Combination therapy regimens including liposomal irinotecan, oxaliplatin and 5-fluorouracil are useful in the treatment of pancreatic cancer, including treatment of patients diagnosed with previously untreated metastatic adenocarcinoma of the pancreas. The combination therapy can include the administration of liposomal irinotecan, oxaliplatin, leucovorin and 5-fluorouracil once every two weeks.
A61K 31/4745 - QuinolinesIsoquinolines ortho- or peri-condensed with heterocyclic ring systems condensed with ring systems having nitrogen as a ring hetero atom, e.g. phenanthrolines
A61K 31/513 - PyrimidinesHydrogenated pyrimidines, e.g. trimethoprim having oxo groups directly attached to the heterocyclic ring, e.g. cytosine
A61K 9/127 - Synthetic bilayered vehicles, e.g. liposomes or liposomes with cholesterol as the only non-phosphatidyl surfactant
A61K 9/00 - Medicinal preparations characterised by special physical form
A61K 31/475 - QuinolinesIsoquinolines having an indole ring, e.g. yohimbine, reserpine, strychnine, vinblastine
A61K 31/436 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a six-membered ring having oxygen as a ring hetero atom, e.g. rapamycin
A61K 47/20 - Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing sulfur, e.g. dimethyl sulfoxide [DMSO], docusate, sodium lauryl sulfate or aminosulfonic acids
The present invention is directed to a polypeptide for use in promoting neuronal growth or neuronal repair to treat a neurological disorder in a subject, wherein the polypeptide comprises: a clostridial neurotoxin light chain (L-chain) or fragment thereof; and/or a fragment of a clostridial neurotoxin heavy chain (H-chain). Additional polypeptides for use in promoting neuronal growth or neuronal repair to treat a neurological disorder in a subject are also provided, as are corresponding methods and uses.
A61K 38/48 - Hydrolases (3) acting on peptide bonds (3.4)
A61P 25/28 - Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
Novel therapies for the treatment of small cell lung cancer (SCLC) include the administration of an antineoplastic therapy consisting of liposomal irinotecan administered once every two weeks, optionally including the administration of other non-antineoplastic agents to the patient such as the administration of a corticosteroid and an anti-emetic to the patient prior to the administration of the irinotecan liposome.
A61K 31/4745 - QuinolinesIsoquinolines ortho- or peri-condensed with heterocyclic ring systems condensed with ring systems having nitrogen as a ring hetero atom, e.g. phenanthrolines
A61K 9/00 - Medicinal preparations characterised by special physical form
A61K 9/127 - Synthetic bilayered vehicles, e.g. liposomes or liposomes with cholesterol as the only non-phosphatidyl surfactant
A61K 31/573 - Compounds containing cyclopenta[a]hydrophenanthrene ring systemsDerivatives thereof, e.g. steroids substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane or progesterone substituted in position 21, e.g. cortisone, dexamethasone, prednisone or aldosterone
The present disclosure relates generally to the field of producing botulinum toxin. More specifically, the present disclosure relates to a method for producing botulinum toxin in a culture medium free or substantially free of animal product. The present disclosure also relates to the culture medium for producing botulinum toxin that is free or substantially free of animal product.
INSTITUTE OF MOLECULAR AND CELL BIOLOGY, BIOMEDICAL SCIENCES INSTITUTES (Singapore)
Inventor
Foster, Keith
Beard, Matthew
Yeo, Jeremy Changyu
Bard, Frederic Andre Jean
Tay, Pei Ling Felicia
Abstract
The present invention is directed to a method for identifying a gene that regulates clostridial neurotoxin activity, the method comprising: a. providing a sample of human neuronal cells expressing a polypeptide that comprises a C-terminal detectable label, wherein the polypeptide is cleavable by a clostridial neurotoxin; b. altering expression of a target gene of the cells; c. contacting the cells with the clostridial neurotoxin; d. measuring an amount of C-terminal detectable label, thereby quantifying clostridial neurotoxin activity; and e. identifying the target gene as a regulator of clostridial neurotoxin activity when the quantified clostridial neurotoxin activity is different to the quantified clostridial neurotoxin activity when expression of the target gene is unaltered; or f. identifying that the target gene is not a regulator of clostridial neurotoxin activity when the quantified clostridial neurotoxin activity is equivalent to the quantified clostridial neurotoxin activity when expression of the target gene is unaltered. Also provided are related methods for identifying an agent that regulates clostridial neurotoxin activity, as well as human neuronal cells, nucleotides, vectors, polypeptides, kits, and compositions suitable for use in the methods of the invention.
G01N 33/50 - Chemical analysis of biological material, e.g. blood, urineTesting involving biospecific ligand binding methodsImmunological testing
C07K 14/435 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from animalsPeptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from humans
88.
CATALYTICALLY INACTIVE CLOSTRIDIAL NEUROTOXINS FOR THE TREATMENT OF PAIN & INFLAMMATORY DISORDERS
The present invention is directed to a polypeptide for use in treating pain or an inflammatory disorder, wherein the polypeptide comprises a clostridial neurotoxin light-chain (L-chain), a clostridial neurotoxin translocation domain (HN domain) and/or a clostridial neurotoxin receptor binding domain (Hc domain), wherein when the polypeptide comprises a clostridial neurotoxin L-chain, the L-chain is catalytically inactive. Also provided are corresponding methods of treatment and uses.
NCC domain), wherein when the polypeptide comprises a clostridial neurotoxin L-chain, the L-chain is catalytically inactive. Also provided are corresponding methods of treatment and uses.
The present invention relates to a method for proteolytically processing a single-chain clostridial neurotoxin into a corresponding di-chain clostridial neurotoxin, the method comprising: providing a single-chain clostridial neurotoxin; and contacting the single-chain clostridial neurotoxin with furin; wherein the single-chain clostridial neurotoxin has an activation loop comprising or consisting of the polypeptide sequence Arg-Xaa-Xaa-Arg; and wherein furin hydrolyses a peptide bond of the activation loop thereby producing a di-chain clostridial neurotoxin. The invention also relates to engineered clostridial neurotoxins and methods for manufacturing the same, as well as related pharmaceutical compositions, nucleotide sequences, and therapeutic and cosmetic uses.
A cell that has been genetically engineered to be highly sensitive to clostridial neurotoxin, for example, botulinum neurotoxin and tetanus neurotoxin, or modified or recombinant versions thereof. A method for making such a genetically-engineered cell and a method for using such a cell in assaying the activity of modified or recombinant clostridial neurotoxin.
ccccinter aliainter alia) corresponding methods for producing the same, methods for selecting oxidation resistant clostridial neurotoxins, nucleic acids encoding the same, and therapeutic uses of said modified clostridial neurotoxins.
The present invention provides a clostridial neurotoxin for use in a method of treating a brain disorder in a patient by promoting a neuroimmune response.
An engineered clostridial neurotoxin comprising an activation loop that comprises an amino acid sequence of the formula Cys-(Xaa)a-Ile-Asp/Glu-Gly-Arg-(Yaa)b-Cys, wherein a is an integer from 1 to 10, b is an integer from 4 to 15, each iteration of Xaa and Yaa individually represents an amino acid, and the engineered clostridial neurotoxin is not BoNT/C1, a method for producing the same, a method of treating a disease or condition comprising administering the engineered clostridial neurotoxin or the corresponding di-chain clostridial neurotoxin, a composition comprising the engineered clostridial neurotoxin or the corresponding di-chain clostridial neurotoxin, and a polynucleotide encoding the engineered clostridial neurotoxin. A method for proteolytically processing a single-chain clostridial neurotoxin into a corresponding di-chain clostridial neurotoxin, the method comprising contacting the single-chain clostridial neurotoxin with enterokinase or factor Xa and a di-chain clostridial neurotoxin produced using such a method. A method for hydrolyzing a peptide bond of a polypeptide comprising contacting the polypeptide with an enterokinase.
The present invention relates to a method for preparing a labelled polypeptide, the method comprising: a. providing a polypeptide comprising: i. a sortase acceptor site or a sortase donor site; ii. a non-cytotoxic protease or a proteolytically inactive mutant thereof; iii. a Targeting Moiety (TM) that is capable of binding to a Binding Site on a target cell; and iv. a translocation domain; b. incubating the polypeptide with: a sortase; and a labelled substrate comprising a sortase donor site or a sortase acceptor site, respectively, and a conjugated detectable label; wherein the sortase catalyses: conjugation between an amino acid of the sortase acceptor site of the polypeptide and an amino acid of the sortase donor site of the labelled substrate; or conjugation between an amino acid of the sortase acceptor site of the labelled substrate and an amino acid of the sortase donor site of the polypeptide; thereby labelling the polypeptide; and c. obtaining the labelled polypeptide. The invention also relates to polypeptides for labelling, labelled polypeptides, nucleic acids encoding said polypeptides, and methods of using and manufacturing said polypeptides.
A method for determining cleavage of a VAMP by a clostridial neurotoxin in a cell that has been contacted with the clostridial neurotoxin under conditions suitable for clostridial neurotoxin activity, the method comprising contacting the cytoplasmic content of the cell with an antibody that binds to a resulting C-terminal product of such cleavage under suitable conditions in vitro or ex vivo and detecting the binding of the antibody to the C-terminal cleavage product. The antibody may, for example, be capable of binding an antigenic polypeptide consisting of 10 to 65 amino acid residues and comprising an epitope comprising an amino acid sequence that is at least 90% identical to an amino acid sequence of at least 8 amino acid residues that is immediately C-terminal to a clostridial neurotoxin cleavage site in the VAMP.
G01N 33/569 - ImmunoassayBiospecific binding assayMaterials therefor for microorganisms, e.g. protozoa, bacteria, viruses
C12Q 1/37 - Measuring or testing processes involving enzymes, nucleic acids or microorganismsCompositions thereforProcesses of preparing such compositions involving hydrolase involving peptidase or proteinase
C07K 14/33 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from bacteria from Clostridium (G)
C07K 14/47 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from animalsPeptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from humans from vertebrates from mammals
C07K 16/12 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from bacteria
C07K 16/18 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans
A method for producing β-trypsin, the method comprising: a) renaturing denatured trypsinogen, thereby producing renatured trypsinogen, wherein the renaturing is carried out in a buffer that comprises L-arginine; b) purifying the renatured trypsinogen by anion 5 exchange chromatography, thereby providing purified renatured trypsinogen; and c) incubating the purified renatured trypsinogen under conditions to promote proteolytic activity of the trypsinogen, wherein trypsinogen is cleaved into β-trypsin by said proteolytic activity; wherein steps a) and b) are carried out under conditions that do not promote the proteolytic activity of trypsinogen; wherein the method does not comprise the addition of a further 10 protease for cleaving trypsinogen into β-trypsin; wherein at least step c) is carried out in a buffer that does not comprise L-arginine; and wherein prior to step c), when present in a buffer that does not comprise L-arginine, the trypsinogen is not subjected to a temperature of >8 °C for more than 38 hours.
Provided are methods for treating pancreatic cancer in a patient by administering liposomal irinotecan (MM-398) alone or in combination with additional therapeutic agents. In one embodiment, the liposomal irinotecan (MM-398) is co-administered with 5-fluorouracil and leucovorin.
A61K 31/4745 - QuinolinesIsoquinolines ortho- or peri-condensed with heterocyclic ring systems condensed with ring systems having nitrogen as a ring hetero atom, e.g. phenanthrolines
A61K 31/573 - Compounds containing cyclopenta[a]hydrophenanthrene ring systemsDerivatives thereof, e.g. steroids substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane or progesterone substituted in position 21, e.g. cortisone, dexamethasone, prednisone or aldosterone
A61K 45/06 - Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
A61K 9/00 - Medicinal preparations characterised by special physical form
A61K 9/127 - Synthetic bilayered vehicles, e.g. liposomes or liposomes with cholesterol as the only non-phosphatidyl surfactant
A61K 31/513 - PyrimidinesHydrogenated pyrimidines, e.g. trimethoprim having oxo groups directly attached to the heterocyclic ring, e.g. cytosine
A61K 31/517 - PyrimidinesHydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with carbocyclic ring systems, e.g. quinazoline, perimidine
A61K 31/519 - PyrimidinesHydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
99.
COLLECTING PHYSICAL THERAPY INFORMATION TO ENHANCE TREATMENT EFFICACY OF BOTULINUM TOXIN
Methods for improving active movement capacity in a subject experiencing muscle impaired or abnormal activity, and software products and computer systems for implementing such methods. A subject having impaired active movement capacity is administered an effective amount of botulinum toxin and instructed to undergo physical therapy, such as through a Guided Self-rehabilitation Contract (GSC), and to record information associated with the physical therapy into, e.g., a software program running on a computer device. The information may be stored in a database, which can be accessed by a medical practitioner who is administering the botulinum toxin. This information is used to improve the clinical management of the subject's impaired active movement capacity.
A61K 38/48 - Hydrolases (3) acting on peptide bonds (3.4)
G16H 20/17 - ICT specially adapted for therapies or health-improving plans, e.g. for handling prescriptions, for steering therapy or for monitoring patient compliance relating to drugs or medications, e.g. for ensuring correct administration to patients delivered via infusion or injection
A61K 9/00 - Medicinal preparations characterised by special physical form
Method of treating or reducing a symptom of traumatic brain injury (TBI) in a subject, comprising administering to the subject a therapeutically-effective amount of botulinum neurotoxin. Composition for use in treating or reducing a symptom of TBI in a subject comprising botulinum neurotoxin. Computer system programmed to receive information related to a subject's response to administration of botulinum neurotoxin, store that response in a database, and transmit the response to a medical practitioner. Non-transitory computer-readable storage medium storing instructions that, when executed by a computer system, causes the computer system to perform the aforementioned steps.
