Abstract: The present invention relates to a modified polypeptide with a biological activity to lyse cell walls of bacteria, wherein the polypeptide has no caspase, clostripain, enterokinase, factor Xa, granzyme B, staphylococcus peptidase I (V8 Protease), plasmin, streptopain, bacillolysin and/or thrombin cleavage site. The invention further relates to nucleic acids with a sequence encoding a polypeptide according to the present invention.

Abstract: A method for treating a patient with migraine headache in accordance with the present invention generally includes administering to the patient a therapeutically effective amount of a Botulinum toxin in a pharmaceutically safe form with the administration being on the trigeminal cervical system, for enabling axonal transport of the neurotoxin from distal to central sites. More specifically, the administration includes extramuscular injection of the neurotoxin over the aponeurotic fascia of the scalp for enabling the neurotoxin to diffuse into distal sensory nerves, in order to enable concentration over the occipital-parietal-frontal head region.

Abstract: The present invention relates to generation and high level expression of recombinant non-toxic of epsilon toxin of Clostridium perfringens as a recombinant vaccine against Clostridium perfringens infection and a process for producing the vaccine involving amplifying, cloning, transforming, incubating and purifying the recombinant non-toxic epsilon toxin protein. Thus in this invention, substitution mutation Y71G was executed in recombinant Etx and the recombinant EtxY71G protein was over-expressed in soluble form. Expressed protein was purified near homogeneity by DEAE sepharose anion exchange chromatography with high yield. Potential of rEtxY71G as a vaccine candidate was evaluated and found to be highly specific and immunogenic. The present invention is the first report for high level expression of non toxic rEtxY71G mutant protein of Clostridium perfringens. Upto 100 mg/L of highly immunogenic and homogeneous recombinant EtxY71G protein of 31 kDa was produced.

Abstract: The specification discloses modified Clostridial toxins comprising an exogenous Clostridial toxin di-chain loop protease cleavage site located within the di-chain loop region; polynucleotide molecules encoding such modified Clostridial toxins; method of producing such modified Clostridial toxins, method of activating such modified Clostridial toxins and methods of activating recombinantly-expressed Clostridial toxins.

Abstract: A method and composition for treating a patient suffering from a disease, disorder or condition and associated pain include the administration to the patient of a therapeutically effective amount of a neurotoxin selected from a group consisting of Botulinum toxin types A, B, C, D, E, F and G.

Abstract: Polyglutamic acid (PGA) formulations are provided for use as a dermal filler. Also provided are methods of use of such formulations for treatment of cosmetic defects.

Abstract: The invention provides active and passive immunization methods for preventing and treating Clostridium difficile infection, which involve percutaneous administration of C. difficile toxin-neutralizing polyclonal immune globulin, C. difficile toxoids, or combinations thereof. Also provided by the invention are C. difficile toxoids, C. difficile toxin-neutralizing polyclonal immune globulin, and methods of identifying subjects that produce C. difficile toxin-neutralizing polyclonal immune globulin.

Abstract: Methods for treating a coronary risk factor (such as hypertension, diabetes, hyperlipidemia and obesity) and/or a respiratory disorder (such as asthma, chronic obstructive pulmonary disease and bronchitis) and/or arthritis by local administration of a botulinum neurotoxin to at least one of a head, neck or shoulder location (for example, by subdermal, subcutaneous or intramuscular administration of the botulinum neurotoxin) of a patient with a coronary risk factor, respiratory disorder or arthritis.

Abstract: Sympathetic nerves run through the adventitia surrounding renal arteries and are critical in the modulation of systemic hypertension. Hyperactivity of these nerves can cause renal hypertension, a disease prevalent in 30-40% of the adult population. Hypertension can be treated with neuromodulating agents (such as angiotensin converting enzyme inhibitors, angiotensin II inhibitors, or aldosterone receptor blockers), but requires adherence to strict medication regimens and often does not reach target blood pressure threshold to reduce risk of major cardiovascular events. A minimally invasive solution is presented here to reduce the activity of the sympathetic nerves surrounding the renal artery by locally delivering neurotoxic or nerve-blocking agents into the adventitia. Extended elution of these agents may also be accomplished in order to tailor the therapy to the patient.

Abstract: The present invention relates to pharmaceutical compositions suitable for the treatment of chronic diseases associated with the presence of abnormal or an abnormal distribution of microflora in the gastrointestinal tract of a mammalian host, which compositions comprise viable non-pathogenic or attenuated pathogenic Clostridia. The compositions further comprise one or more additional viable non-pathogenic or attenuated pathogenic microorganisms selected from the group consisting of Bacteroides, Eubacteria, Fusobacteria, Propionibacteria, Lactobacilli, anaerobic cocci, Ruminococcus, E.Coli, Gemmiger, Desullomonas, Peptostreptococcus, and fungi. The present invention also provides pharmaceutical compositions suitable for the treatment of the same chronic diseases comprising viable non-pathogenic or attenuated pathogenic Escherichia coli, at least one strain of viable non-pathogenic or attenuated pathoenic Bacteroides and at least one strain of viable non-pathogenic or attenuated pathogenic microorganism.

Abstract: The specification discloses modified Clostridial toxins comprising a Clostridial toxin enzymatic domain, a Clostridial toxin translocation domain and an enhanced Clostridial toxin binding domain; polynucleotide molecules encoding such modified Clostridial toxins; and method of producing such modified Clostridial toxins.

Abstract: A single polypeptide is provided which comprises first and second domains. The first domain enables the polypeptide to cleave one or more vesicle or plasma-membrane associated proteins essential to exocytosis, and the second domain enables the polypeptide to be translocated into a target cell or increases the solubility of the polypeptide, or both. The polypeptide thus combines useful properties of a clostridial toxin, such as a botulinum or tetanus toxin, without the toxicity associated with the natural molecule. The polypeptide can also contain a third domain that targets it to a specific cell, rendering the polypeptide useful in inhibition of exocytosis in target cells. Fusion proteins comprising the polypeptide, nucleic acids encoding the polypeptide and methods of making the polypeptide are also provided. Controlled activation of the polypeptide is possible and the polypeptide can be incorporated into vaccines and toxin assays.

Abstract: A method for treating skin by administration of a neurotoxin such as a botulinum toxin by means of a dry needle. The method can be used to accomplish what has generally been described as skin rejuvenation and also to treat skin disorders such as skin lines, crepiness, excess skin, wrinkles, platysmal bands, uneven skin tone and color, and hyperhidrosis.

Abstract: A composition and dosage regime including a vaccine and levamisole for the treatment of clostridial diseases and helminthiasis. New methods of administration relating to particular dosage regimes of such a composition are also claimed.

Abstract: Provided herein are methods for generating dry vaccine powder formulations. Dry vaccine powder formulations can be used for intranasal delivery. Also provided are methods for stimulating local mucosal and systemic immunity by intranasal vaccine delivery.

Abstract: The present invention provides compositions and systems for delivery of nanocarriers to cells of the immune system. The invention provides nanocarriers capable of stimulating an immune response in T cells and/or in B cells. The invention provides nanocarriers that comprise an immunofeature surface and an immunostimulatory moiety. In some embodiments, the immunostimulatory moiety is an adjuvant. The invention provides pharmaceutical compositions comprising inventive nanocarriers. The present invention provides methods of designing, manufacturing, and using inventive nanocarriers and pharmaceutical compositions thereof.

Abstract: The disclosure provides a method of preparing an immunologically-active adjuvant-bound freeze dried vaccine composition. A specific embodiment provides a stable vaccine composition comprising an aluminum-salt adjuvant, a recombinant Clostridium botulinum neurotoxin protein and a glass-forming agent. These vaccine compositions are useful in the treatment of humans and other animals at risk of infection from Clostridium botulinum neurotoxin.

Abstract: A novel subtype of type A botulinum neurotoxin (BoNT/A) is disclosed in the application. Methods to purify the neurotoxin as well as uses thereof are also disclosed.

Abstract: An immunogenic composition comprising a Hib saccharide conjugate and at least two further bacterial saccharide conjugates is provided, wherein the Hib conjugate is present in a lower saccharide dose than the mean saccharide dose of all the at least two further bacterial saccharide conjugates.

Abstract: Metal-containing materials, as well as their preparation, formulations, and use are disclosed.

Abstract: A method for selection and treatment of externally caused migraine headache, the method includes identifying a patient group having chronic migraine headache; determining the identified patient group, a specific patient with a post traumatic migraine headache; and administering to the selected patient by injection of a therapeutically effective amount of a Botulinum neurotoxin in a pharmaceutically safe form to the selected patient's head or upper neck; administration preferably being on the sites of the trigeminal cervical system, enabling axonal transport of the neurotoxin from distal to central sites; and the administration preferably comprising extramuscular injection of the neurotoxin of suitable dilution (a) over the aponeurotic fascia, or (b) intra-orally, in a foramina of the sphenopalatine ganglion, or (c) to emerging exit points of nerves including foraminal sites.

Abstract: Methods for treating conditions in an animal or human subject. The conditions may be pain, skeletal muscle conditions, smooth muscle conditions, glandular conditions and cosmetic conditions. The methods comprise the step of administering a Clostridium neurotoxin component or Clostridium neurotoxin component encoding DNA to the subject using a needleless syringe.

Abstract: Methods are disclosed herein for treating depression in the subject. A method includes the use of Botulinum toxin to cause paralysis of a facial muscle, such as the depressor anguli oris, procerus, frontalis, orbicularis oculi, or corrugator supercilii muscle to treat depression in the subject.

Abstract: Chromatographic processes and systems for purifying a botulinum toxin from an APF fermentation medium.

Abstract: The present invention is directed to pharmaceutical agents and compositions useful for the treatment and prevention of amyloid disease in a subject. The invention further relates to isolated antibodies that recognize a common conformational epitope of amyloidogenic proteins or peptides that are useful for the diagnosis, treatment, and prevention of amyloid disease.

Abstract: A composition for topical application of a botulinum toxin (including botulinum toxin derivatives) comprises a botulinum toxin and a carrier comprising a polymeric backbone comprising a long-chain polypeptide or nonpeptidyl polymer having attached positively charged branching or “efficiency” groups. The invention also relates to methods for reducing muscle paralysis and other conditions that may be treated with a botulinum toxin, particularly paralysis of subcutaneous, and most particularly, facial, muscles, by topically applying an effective amount of the botulinum toxin and carrier, in conjunction, to the subject's skin or epithelium. Kits for administration are also described.

Abstract: A composition for topical application of a botulinum toxin (including botulinum toxin derivatives) comprises a botulinum toxin and a carrier comprising a polymeric backbone comprising a long-chain polypeptide or nonpeptidyl polymer having attached positively charged branching or “efficiency” groups. The invention also relates to methods for reducing muscle paralysis and other conditions that may be treated with a botulinum toxin, particularly paralysis of subcutaneous, and most particularly, facial, muscles, by topically applying an effective amount of the botulinum toxin and carrier, in conjunction, to the subject's skin or epithelium. Kits for administration are also described.

Abstract: A pharmaceutical preparation comprising one of the botulinum neurotoxins from Clostridium botulinum of types A, B, C, D, E, F or G or a mixture of two or more of these neurotoxins, wherein the neurotoxin or the mixture of neurotoxins is free of the complexing proteins which naturally form the botulinum neurotoxin complexes together with the neurotoxins.

Abstract: Disclosed herein are methods of using extracellular matrix digesting enzymes and neurotoxins, such as a Clostridial neurotoxins, to treat various medical conditions, such as overactive bladder, benign prostatic hyperplasia, hyperhidrosis, for example.

Abstract: Disclosed herein are methods of using extracellular matrix digesting enzymes and neurotoxins, such as a Clostridial neurotoxins, to treat various medical conditions, such as overactive bladder, benign prostatic hyperplasia, hyperhidrosis, and cholecystitis for example.

Abstract: Methods for enhancing destruction and killing of bacterial spores via phagocytosis, where phagocytosis of bacterial spores is enhanced by using a glycoconjugate. In one embodiment, the method includes the steps of modifying a surface of a bacterial spore to increase adherence to a phagocyte; and ingesting the adherence-increased spore with the phagocyte, thereby destructing and killing the spore by blocking spore-induced phagocyte cell death, while increasing phagocyte activation level and production of antimicrobial and cytocidal agents such as NO and inflammatory cytokines. The adherence of spore to a phagocyte is increased after the surface thereof is coated with a glycoconjugate to form a glycoconjugate-coated spores. The glycoconjugate-coated spores also increase ingestion of the spores by phagocytes and facilitate phagosome-lysosome fusion, which in turn results in destruction and killing of bacterial spores via phagocytosis.

Abstract: The present invention pertains to pharmaceutical compositions which comprise a botulinum neurotoxin from Clostridium botulinum, the neurotoxin being free of the complexing proteins naturally present in the botulinum neurotoxin complex or being chemically modified or being modified by genetic manipulation. Moreover the pharmaceutical compositions of the instant invention have good stability and are advantageously formulated free of human serum albumin.

Abstract: The invention provides compositions and methods for treating incontinence associated with sexual activity.

Abstract: Described is a method of treating chronic compartment syndrome in a muscle of a mammal, particularly exertional compartment syndrome. The method includes introducing an effective amount of a nerve-blocking toxin, such as human botulinum toxin into the muscle. In addition to treating chronic or exertional compartment syndrome, a method is included and described of confirming diagnosis of exertional compartment syndrome in a muscle of a mammal. In the method, venous compression and/or expansion in a mammal in an area of a muscle having a symptom associated with exertional compartment syndrome is evaluated by comparing venous flow at rest and after stress on the muscle. An anaesthetic is used to block a nerve supplying motor function to the muscle causing compression of a blood vessel.

Abstract: A method is disclosed for blocking or reducing physiological reaction in a mammal to the interaction of IgE antibodies present in said mammal upon contact with the corresponding antigen, by the administration to said mammal of a therapeutically effective amount of a neurotoxin (CnT) derived from Clostridia sp.

Abstract: This invention provides botulinum antitoxin compositions and methods of production, and methods of treating animals and humans prophylactically and also those suspected of having contacted botulism toxin. The botulinum antitoxin is prepared by inoculating an animal with a monovalent botulinum toxoid and toxin. The animal's plasma is collected and purified at a high pH by affinity chromatography. The resulting monovalent immunoglobulins are de-speciated by digestion with pepsin. Monovalent antitoxins for all seven botulinum serotypes are then combined to produce a high titered heptavalent botulinum antitoxin composition.

Abstract: The present invention describes novel nanoparticle compositions, and systems and methods utilizing them for treating disorders and/or conditions associated with the epidermal and/or dermal level of the skin. Such disorders include acne, hyperhidrosis, bromhidrosis, chromhidrosis, rosacea, hair loss, dermal infection, actinic keratosis, facial wrinkles, muscle contracture, and headache. Methods generally involve administering nanoparticle compositions to the skin.

Abstract: A method using a pharmaceutical composition comprising botulinum toxin and a pharmacologically acceptable carrier to treat pain in the knee joint caused by saphenous nerve entrapment. The composition of the present invention is for subcutaneous injection above the medial side of the knee.

Abstract: The present specification discloses methods of treating a psychological trauma in an individual using botulinum toxins and/or a Targeted Exocytosis Modulator, and compositions thereof.

Abstract: Methods for prolongation of climax time in a patient in need thereof are presented, as are methods for treating premature ejaculation by local administration of a Clostridial neurotoxin, such a botulinum neurotoxin, to the patient, are provided.

Abstract: A high potency botulinum toxin pharmaceutical composition comprising two excipients (such as albumin and sodium chloride) in a weight to weight ratio of between about 1 and about 100.

Abstract: Liposomes are used for intravesical drug delivery, especially delivery of botulinum toxin (BoNT) to help improve lower urinary tract symptoms by decreasing bladder irritation and frequency. The system uses a lower and safer dose of BoNT with lower risk of urinary retention. A simple instillation of liposome-BoNT as a liquid formulation into the bladder, in a typical volume of 30-60 ml, will achieve efficacy similar to that currently achieved with cystscopic needle injection of BoNT. The dose may be lower than that done by injection, thereby causing significantly less risk of urinary retention. Liposome-BoNT can protect the BoNT from bladder and urine breakdown. Liposome-BoNT instillation is more comfortable for the patients and allows many more doctors' offices to offer this form of treatment that would otherwise be restricted to doctors skilled and certified in cystoscopic BoNT injection.

Abstract: The embodiment described herein are related nanoemulsions comprising botulinum toxins. In one embodiment, the nanoemulsions are prepared by high pressure microfluidization and comprise a particle size distribution exclusively between 10 and 300 nm. The nanoemulsions contemplated by the present invention are useful for the cosmetic and medical treatment of muscular contracture states. For example, botulinum toxin may relax facial muscles such that skin wrinkles become smoother and less noticeable. Further, the present invention contemplates a cosmetic formulation that may be self-administered, for example, in the privacy of one's home and without medical supervision.

Abstract: The invention relates to a modified botulinum toxin comprising a natural heavy chain and a modified light chain, characterized in that the modification of the light chain resides in that it comprises (i) an extension of the chain on its N-terminus which has the structure —(C)n-(tag)m-(X)l- in the direction from the N- to the C-terminal end, wherein C represents a cysteine residue, tag represents any tag and X represents the residue of any naturally occurring amino acid, n represents an integer from 1 to 50, m represents 0 or 1, and l represents 0 or an integer from 1 to 50, and in that (ii) at least one of the cysteine residues in the extension of the chain is coupled to at least one chain of PEG.

Abstract: Improved efficacy in treatment of rhinitis with botulinum toxin is obtained using liposomal encapsulated botulinum formulations for administration of the botulinum toxin. The liposomes are typically administered in a physiologically acceptable carrier such as saline or phosphate buffered saline by instillation into the nasal passages.

Abstract: The present specification discloses TEMs, compositions comprising such TEMs, compositions comprising such TEMs and Clostridial toxins, methods of treating an involuntary movement disorder in an individual using such compositions, use of such TEMs in manufacturing a medicament for treating an involuntary movement disorder, use of such TEMs and Clostridial toxins in manufacturing a medicament for treating an involuntary movement disorder, use of such TEMs in treating an involuntary movement disorder, and use of such TEMs and Clostridial toxins in treating an involuntary movement disorder.

Abstract: The present specification discloses TEMs, compositions comprising such TEMs, compositions comprising such TEMs and Clostridial toxins, methods of treating a neuroendocrine disorder in an individual using such compositions, use of such TEMs in manufacturing a medicament for treating a neuroendocrine disorder, use of such TEMs and Clostridial toxins in manufacturing a medicament for treating neuroendocrine disorder, use of such TEMs in treating a neuroendocrine disorder, and use of such TEMs and Clostridial toxins in treating a neuroendocrine disorder.

Abstract: The present specification discloses Clostridial neurotoxins and TEMs, compositions comprising such Clostridial neurotoxins and TEMs, methods of treating a multiple medical disorder in an individual using such compositions, use of such Clostridial neurotoxins and TEMs in manufacturing a medicament for treating a multiple medical disorder, and uses of such Clostridial neurotoxins and TEMs in treating a multiple medical disorder.

Abstract: Disclosed herein are compositions and methods for treating nasal and sinus conditions, and symptoms thereof, with botulinum toxin (BoNT).

Abstract: A liquid or semi-solid formulation of botulinum toxin for the preparation of a medicament intended to treat a disorder characterized by bladder spasms (e.g. urinary incontinence due to unstable bladder or unstable detrusor sphincter, voiding complications due to detrusor overactivity or unstable detrusor sphincter, urinary retention secondary to spastic sphincter or hypertrophied bladder neck and neurogenic bladder dysfunction secondary to Parkinson's disease, spinal cord injury, stroke or multiple sclerosis or characterized by a spasm reflex), wherein said medicament is for administration by infusion into the bladder or by other methods that do not involve injection into the bladder wall.