Classifications

• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K39/00—Medicinal preparations containing antigens or antibodies
  • A61K39/385—Haptens or antigens, bound to carriers
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K38/00—Medicinal preparations containing peptides
  • A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
  • A61K38/162—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from virus
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K38/00—Medicinal preparations containing peptides
  • A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
  • A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
  • A61K38/22—Hormones
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K39/00—Medicinal preparations containing antigens or antibodies
  • A61K39/0005—Vertebrate antigens
  • A61K39/0007—Nervous system antigens; Prions
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
  • A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
  • A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting 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
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
  • A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting 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
  • A61K47/69—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting 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
  • A61K47/6901—Conjugates being cells, cell fragments, viruses, ghosts, red blood cells or viral vectors
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K9/00—Medicinal preparations characterised by special physical form
  • A61K9/0012—Galenical forms characterised by the site of application
  • A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
  • A61P25/00—Drugs for disorders of the nervous system
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
  • A61P25/00—Drugs for disorders of the nervous system
  • A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
  • A61P25/16—Anti-Parkinson drugs
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
  • A61P25/00—Drugs for disorders of the nervous system
  • A61P25/28—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
• • C—CHEMISTRY; METALLURGY
  • C07—ORGANIC CHEMISTRY
  • C07K—PEPTIDES
  • C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K39/00—Medicinal preparations containing antigens or antibodies
  • A61K2039/51—Medicinal preparations containing antigens or antibodies comprising whole cells, viruses or DNA/RNA
  • A61K2039/525—Virus
  • A61K2039/5258—Virus-like particles
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K39/00—Medicinal preparations containing antigens or antibodies
  • A61K2039/60—Medicinal preparations containing antigens or antibodies characteristics by the carrier linked to the antigen
  • A61K2039/6031—Proteins
  • A61K2039/6075—Viral proteins

Definitions

• the present invention relates to novel uses of a construct consisting of virus-like particle (VLP) structure chemically coupled to a fragment of the A ⁇ -1-42 peptide and its pharmaceutically acceptable salts (hereinafter CONSTRUCT), in particular to dosage regimens, modes of and dosage forms for the administration of a CONSTRUCT for the treatment of patients suffering from dementia, in particular dementia of the Alzheimer's type, especially mild to moderate or severe Alzheimer's Disease (AD), and vascular dementia with amyloid angiopathy to a method of isolating immune cells, especially antibody producing cells, and antibodies as well as there genes or fragments thereof generated by the immune system of a warm-blooded animal, especially a human, in response to the administration of the CONSTRUCT, the production of such antibodies and the pharmaceutical use of such antibodies.
• VLP virus-like particle
• CONSTRUCT pharmaceutically acceptable salts
• the present invention relates to novel uses of a construct consisting of virus-like particle (VLP) structure chemically coupled to a fragment of the A ⁇ -1-42 peptide and its pharmaceutically acceptable salts (hereinafter CONSTRUCT), in particular to dosage regimens, modes of and dosage forms for the administration of a CONSTRUCT for the treatment of patients with increased A ⁇ -level , including but not limited to patients with dementia associated with Parkinson's disease, Lewy Body dementia.
• VLP virus-like particle
• CONSTRUCT pharmaceutically acceptable salts
• the present invention also relates to novel uses of a construct consisting of virus-like particle (VLP) structure chemically coupled to a fragment of the A ⁇ -1-42 peptide and its pharmaceutically acceptable salts (hereinafter CONSTRUCT), in particular to dosage regimens, modes of and dosage forms for the administration of a CONSTRUCT for the prophylactic treatment of subjects at risk of developing AD, including but not limited to subjects with mild cognitive impairment , subjects with genotypes known to be associated with AD, such as ApoE4, subjects with Trisomy 21 and subjects with surrogate markers indicating risk for AD.
• VLP virus-like particle
• CONSTRUCT pharmaceutically acceptable salts
• AD Alzheimer's disease-modifying therapy for AD is likely to include products that affect the deposition of ⁇ -amyloid in the brain.
• a ⁇ -specific antibodies actively generated by the immune system or passively administered, consistently reduce plaque burden in different transgenic mouse models for A ⁇ -amyloidosis.
• CONSTRUCTS consisting of a VLP chemically coupled to the A ⁇ -1-6 peptide.
• the CONSTRUCT advantageously can be applied subcutaneously to warm-blooded animals, especially humans, suffering from dementia.
• the CONSTRUCT advantageously can be applied intramuscularly, intranasally and orally to warm-blooded animals, especially humans, suffering from dementia.
• the present invention provides a dosage form for subcutaneous administration of the CONSTRUCT.
• the preferred dosage form for subcutaneous administration of the CONSTRUCT is an aqueous solution containing Phosphate Buffer Saline (PBS), between 0.25 and 0.75 mg/mL CONSTRUCT, preferably between 0.4 and 0.6 mg/mL, e.g. 0.5 mg/mL CONSTRUCT, and no further excipients.
• PBS Phosphate Buffer Saline
• the dosage form can be kept frozen until shortly before usage.
• the dosage form is administered preferably by subcutaneous injection with a syringe to the warm-blooded animal, especially into the abdomen. For thawing of the dosage form, the dosage form can be kept at ambient temperature for about between 15 minutes and 45 minutes, e.g. 30 minutes.
• the vials are gently inverted several times for dispersion of potential sub-visual particles.
• WO 00/3227 to Cytos discloses a technology for providing a construct comprising a core- particle (such as a VLP), a linker and an antigen, all together forming an ordered and repetitive antigen array.
• WO 02/056907 to Cytos and Novartis describes constructs comprising a VLP comprising recombinant proteins of a bacteriophage, such as Q ⁇ , a linker and an antigen, e.g. A ⁇ 1-42 or a fragment thereof, all together forming an ordered and repetitive antigen array.
• a CONSTRUCT as used herein consists of capsid proteins of a RNA bacteriophage, more preferably of capsid proteins of the RNA bacterio ⁇ phage Q ⁇ , self-assembled into a highly ordered VLP structure chemically coupled with a bivalent linker to a fragment of the A ⁇ 1-42 peptide, more preferably to A ⁇ -1-6.
• the CONSTRUCT can be prepared, purified and administered as disclosed in WO 00/3227, WO 02/056907 or WO2004/016282, especially in Example 13, which patent filings as well as the references cited therein are incorporated by reference into the present patent application, especially the end products of the Examples.
• treatment relates in particular to a treatment aiming to halt pathogenic processes that lead to disease progression and/or has symptomatic effects.
• ..prophylactic treatment as used herein relates in particular to a treatment aiming to halt pathogenic processes leading to disease.
• the term ..dementia of the Alzheimer's type as used herein relates in particular to a disease as defined according to the Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV) criteria.
• the present invention relates to a method of treatment of dementia in human patients comprising administering 5 to 175 ⁇ g, preferably 15 to 125 ⁇ g, more preferably about 25 to 100 ⁇ g, e.g. 50 ⁇ g or 75 ⁇ g, of the CONSTRUCT to human patients in need thereof about every 4 to 8 weeks, preferably about every 5 to 7 weeks, in particular about every 6 weeks.
• the present invention relates to a method of treatment of dementia in human patients comprising administering 5 to 1000 ⁇ g, preferably 5 to 300 ⁇ g, more preferably about 50 to 200, most preferably 50-150 ⁇ g, e.g. 50 ⁇ g or 75 ⁇ g,100 ⁇ g, 125 ⁇ g, 150 ⁇ g of the CONSTRUCT to human patients in need thereof about every 4 to 8 weeks, preferably about every 5 to 7 weeks, in particular about every 6 weeks.
• Frequency of injection can vary depending on the patient response. For example the frequency of administration can vary if the injection has to be administered according to antibody titers.
• Suitable clinical studies are in particular randomized, double-blind, placebo-controlled, parallel studies in Alzheimer's patients or open label studies .
• the present invention pertains to a combination comprising at least one CONSTRUCT and at least one nootropic agent, preferably one cholinesterase-inhibitor, or memantine.
• nootropic agent includes, but is not limited to nootropic plant extracts, calcium antagonists, cholinesterase inhibitors, dihydroergotoxin, nicergoline, piracetame, purine derivates, pyritinol, vincamine and vinpocetine.
• nootropic plant extracts includes, but is not limited to extracts from Ginkgo leafs.
• calcium antagonists includes, but is not limited to cinnarizine and nimodipine.
• cholinesterase inhibitors includes, but is not limited to donepezil hydrochloride, rivastigmine and galantamine hydrobromide.
• purine derivates includes, but is not limited to pentifyllin.
• Extracts from Ginkgo leafs can be administered, e.g., in the form as marketed, e.g. under the trademark GinkodilatTM according to the information provided by the package insert.
• Cinnarizine can be administered, e.g., in the form as marketed, e.g. under the trademark Cinnarizin forte-ratiopharmTM.
• Nimodipine can be administered, e.g., in the form as marketed, e.g. under the trademark NimotopTM.
• Donepezil hydrochloride can be administered, e.g., in the form as marketed, e.g. under the trademark AriceptTM.
• Rivastigmine can be prepared as disclosed in US 5,602,176.
• Galantamine hydrobromide can be administered, e.g., in the form as marketed, e.g. under the trademark ReminylTM.
• Dihydroergotoxin can be administered, e.g., in the form as marketed, e.g. under the trademark HyderginTM.
• Nicergoline can be administered, e.g., in the form as marketed, e.g. under the trademark SermionTM.
• Piracetam can be administered, e.g., in the form as marketed, e.g. under the trademark CerebroforteTM.
• Pentifyllin can be administered, e.g., in the form as marketed, e.g. under the trademark CosaldonTM.
• Pyritinol can be administered, e.g., in the form as marketed, e.g. under the trademark EncephabolTM.
• Vinpocetin can be administered, e.g., in the form as marketed, e.g. under the trademark CavintonTM.
• Memantine can be administered, e.g., in the form as marketed, e.g. under the trademarks AxuraTM or NamendaTM.
• the present invention pertains also to a combination comprising a CONSTRUCT of the invention, and at least one nootropic agent selected from the group consisting of nootropic plant extracts, calcium antagonists, cholinesterase inhibitors, dihydroergotoxin, nicergoline, piracetame, purine derivates, pyritinol, vincamine and vinpocetine or memantine, in which the active ingredients are present in each case in free form or in the form of a pharmaceutically acceptable salt and optionally at least one pharmaceutically acceptable carrier, for simultaneous, separate or sequential use, especially for use in a method of treating dementia.
• a CONSTRUCT of the invention and at least one nootropic agent selected from the group consisting of nootropic plant extracts, calcium antagonists, cholinesterase inhibitors, dihydroergotoxin, nicergoline, piracetame, purine derivates, pyritinol, vincamine and vinpocetine or memantine, in which the active ingredients are present in each
• Such a combination is preferably a combined preparation.
• agents can be used in combination with the CONSTRUCT, for example: antidepressants such as SSRIs, SNRIs, NRIs, antipsychotics such as risperidone, antidiabetic treatments such as insulin or metformin, antioxidative treatments such as selegiline, vitamin E, anti-inflammatory treatments such as NSAIDs, lipid-lowering agents such as statins, hormone substitution such as estrogens, amyloid lowering agents such as abeta secretase inhibitors, aggregation inhibitors such as beta-sheet blockers, chelators, immunomodulatory agents such as glatiramer acetate.
• antidepressants such as SSRIs, SNRIs, NRIs
• antipsychotics such as risperidone
• antidiabetic treatments such as insulin or metformin
• antioxidative treatments such as selegiline
• vitamin E anti-inflammatory treatments
• lipid-lowering agents such as statins
• hormone substitution such as estrogens
• amyloid lowering agents
• a combined preparation defines especially a "kit of parts" in the sense that the active ingredients as defined above can be dosed independently or by use of different fixed combinations with distinguished amounts of the ingredients, i.e., simultane- ously or at different time points.
• the parts of the kit can then, e.g., be administered simulta ⁇ neously or chronologically staggered, that is at different time points and with equal or different time intervals for any part of the kit of parts.
• the time intervals are chosen such that the effect on the treated disease in the combined use of the parts is larger than the effect which would be obtained by use of only any one of the active ingredients.
• the present invention also provides
• a commercial package comprising a combination as disclosed herein together with instructions for simultaneous, separate or sequential use thereof in the treatment of dementia, in particular Alzheimer's disease.
• the combination partner (b) is a cholin- esterase inhibitor, especially rivastigmine, or memantine.
• a dosage and mode of administration can be applied as provided in the package inserts.
• the following dosages of the combination partners (b) can be administered to the patient:
• Cinnarizine may be administered to a patient in a total daily dosage of between about 75 to about 150 mg.
• Nimodipine may be administered to a patient in a total daily dosage of between about 60 to about 120 mg.
• Donepezil hydrochloride may be administered to a patient in a total daily dosage of between about 5 mg and 10 mg.
• Rivastigmine may be administered to a patient in a total daily dosage of between about 6 and about 12 mg.
• Galantamine may be administered to a patient in a total daily dosage of between about 12 and 24 mg, e.g. 12 mg twice daily.
• Dihydroergotoxin may be administered in the form of its methansulfonate to a patient in a total daily dosage of between about 4 mg and 10 mg, e.g. about 8 mg.
• Nicergoline may be administered in the form of its tartrate by intramuscular injection to a patient in a total daily dosage of between about 4 mg and 8 mg.
• Piracetam may be administered to a patient in a total daily dosage of between about 1200 and 5000 mg, e.g. 4800 mg/day.
• Pentifyllin may be administered to a patient in a total daily dosage of between about 400 and 800 mg.
• Pyritinol may be administered in the form of its hydrochloride to a patient in a total daily dosage of about 600 mg.
• Vinpocetin may be administered to a patient in a total daily dosage of between about 10 and 15 mg.
• Memantine may be administered to a patient in the form of memantine hydrochloride in a total daily dosage of about 20 mg.
• the present invention provides human monoclonal antibodies against A ⁇ 1-42 induced by the CONSTRUCT, preferably A ⁇ antibodies recognizing the N-terminus of A ⁇ 1-42.
• Examples 1 to 4 male and female patients are included aged between 50 to 80 years (both inclusive), with mild to moderate AD as confirmed by a MMSE score of 16 to 26 (both inclusive), who are outpatients with caregivers (living together or, if living alone, with daily contact), who meet the DSM-IV criteria for dementia of the Alzheimer's type, and who satisfy the criteria for a clinical diagnosis of probable AD according to the National Institute of Neurological and Communicative Disorders and Stroke (NINCDS-ADRDA).
• NINCDS-ADRDA National Institute of Neurological and Communicative Disorders and Stroke
• Each patient participates in a 4-week screening period (Day -28 to Day -1 ), a baseline period (pre-dose on Day 1 in week 0), three single dose treatments under ambulatory conditions in weeks 0, 6 and 18 (Days 1 , 43, 127), ten additional ambulatory visits in bi- to four weekly intervals in weeks 2, 4, 8, 12, 16, 20, 22, 26, 30, and 34 (i.e. on Study Days 15, 29, 57, 85, 113, 141 , 155, 183, 211 and 239), and two additional ambulatory visits in week 42 and 52 (i.e. on Study Days 295 and 365).
• Safety assessments include general physical examinations, neurological examinations, 12-lead electrocardiograms (ECGs), vital signs, standard clinical laboratory evaluations (hematology, blood chemistry, urinalysis), special immunological laboratory evaluations in blood and cerebrospinal fluid (CSF), cerebral magnetic resonance imagings (MRIs), as well as adverse event and serious adverse event monitoring. Further, patients and caregivers are instructed (verbally and in writing) to look for any unexpected deterioration in health status.
• ECGs electrocardiograms
• CSF cerebrospinal fluid
• MRIs cerebral magnetic resonance imagings
• a ⁇ -antibody response is measured by determination of the A ⁇ -antibody titer (IgG and IgM) in serum and CSF using ELISA methods.
• the ex vivo A ⁇ -antibody binding properties in serum and CSF is explored by immunological methods on human and ⁇ -amyloid precursor protein (APP) transgenic mouse brain tissue.
• the VLP-antibody titer response in serum is measured to investigate the immune response to the carrier compound in relation to the immune response to A ⁇ .
• Exploratory pharmacodynamic assessments include the following assessments: 1) determination of disease related markers in CSF (A ⁇ peptides and its isoforms, tau protein and its isoforms, phospho-tau) and plasma (A ⁇ peptides and isoforms); 2) volumetric MRIs, and 3) neuropsychological test battery, mini-mental state examination (MMSE), clinical dementia rating (CDR) and Alzheimer's Disease Cooperative Study - Activities of Daily Living (ADCS-ADL), 4) Positron emission tomography (PET) with n C-Pittsburgh Compound-B ( 11 C- PIB) which is a novel beta-amyloid selective tracer developed for in vivo detection of ⁇ - amyloid plaques in the brain and 18 F-fluorodeoxyglucose ( 18 FDG) Responders are defined as those patients who show a significant increase of A ⁇ -specific antibody titers above baseline and who show an antibody isotype switch from IgM to IgG in serum at latest after the 3r
• Example 1 A single or multi center, randomized, double-blind, placebo-controlled study in patients with mild to moderate Alzheimer's Disease (AD) with three subcutaneous injections of 25 u ⁇ of CONSTRUCT
• a total of 30 patients is randomized to receive three s.c. injections of the CONSTRUCT or placebo.
• 24 patients receive the active drug CONSTRUCT and 6 patients receive placebo under double-blind conditions.
• Three s.c. injections of 25 ⁇ g CONSTRUCT or placebo are administered to each patient in weeks 0, 6 and 18.
• Example 2 A single or multicenter, randomized, double-blind, placebo-controlled study in patients with mild to moderate Alzheimer's Disease (AD) with three subcutaneous injections of 50 uo of CONSTRUCT
• a total of 30 patients is randomized to receive three s.c. injections of the CONSTRUCT or placebo.
• 24 patients receive the active drug CONSTRUCT and 6 patients receive placebo under double-blind conditions.
• Three s.c. injections of 50 ⁇ g CONSTRUCT or placebo are administered to each patient in weeks 0, 6 and 18.
• Example 3 A single or multicenter. randomized, double-blind, placebo-controlled study in patients with mild to moderate Alzheimer's Disease (AD) with three subcutaneous injections of 100 uo of CONSTRUCT
• AD Alzheimer's Disease
• Blood samples are taken by direct venipuncture. A total of 10 ml_ venous blood is collected in plain barrier tubes. The sample are allowed to clot during 45 minutes at room temperature and then centrifuged for 10 minutes at approximately 2500 g. Serum tubes are frozen within 60 min after venipuncture and kept at ⁇ -70°C pending analysis.
• Example 5 A single or multicenter. randomized, double-blind, placebo-controlled study in patients with mild to moderate Alzheimer's Disease (AD) with three subcutaneous injections of 150 u ⁇ of CONSTRUCT
• a total of 30 patients is randomized to receive three s.c. injections of the CONSTRUCT or placebo.
• 24 patients receive the active drug CONSTRUCT and 6 patients receive placebo under double-blind conditions.
• Three s.c. injections of 150 ⁇ g CONSTRUCT or placebo are administered to each patient in weeks 0, 6 and 18.
• Example 6 A single or multicenter, randomized, double-blind, placebo-controlled study in patients with mild to moderate Alzheimer's Disease (AD) with three subcutaneous injections of 300 ug of CONSTRUCT
• a total of 30 patients is randomized to receive three s.c. injections of the CONSTRUCT or placebo.
• 24 patients receive the active drug CONSTRUCT and 6 patients receive placebo under double-blind conditions.
• Three s.c. injections of 300 ⁇ g CONSTRUCT or placebo are administered to each patient in weeks 0, 6 and 18.

Landscapes

• Health & Medical Sciences (AREA)
• Life Sciences & Earth Sciences (AREA)
• Chemical & Material Sciences (AREA)
• Medicinal Chemistry (AREA)
• General Health & Medical Sciences (AREA)
• Veterinary Medicine (AREA)
• Pharmacology & Pharmacy (AREA)
• Public Health (AREA)
• Animal Behavior & Ethology (AREA)
• Epidemiology (AREA)
• Engineering & Computer Science (AREA)
• Bioinformatics & Cheminformatics (AREA)
• Immunology (AREA)
• Neurosurgery (AREA)
• Biomedical Technology (AREA)
• Neurology (AREA)
• Proteomics, Peptides & Aminoacids (AREA)
• Organic Chemistry (AREA)
• Gastroenterology & Hepatology (AREA)
• Virology (AREA)
• Mycology (AREA)
• Microbiology (AREA)
• Chemical Kinetics & Catalysis (AREA)
• General Chemical & Material Sciences (AREA)
• Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
• Endocrinology (AREA)
• Zoology (AREA)
• Hematology (AREA)
• Cell Biology (AREA)
• Dermatology (AREA)
• Biochemistry (AREA)
• Hospice & Palliative Care (AREA)
• Psychiatry (AREA)
• Biophysics (AREA)
• Genetics & Genomics (AREA)
• Molecular Biology (AREA)
• Psychology (AREA)
• Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
• Peptides Or Proteins (AREA)
• Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Priority Applications (12)

Applications Claiming Priority (2)

Related Child Applications (2)

Publications (1)

Family

ID=33523293

Family Applications (1)

Country Status (25)

Cited By (2)

Families Citing this family (2)

Citations (2)

Family Cites Families (55)

• 2004
  • 2004-11-05 GB GB0424563A patent/GB0424563D0/en not_active Ceased
• 2005
  • 2005-10-28 MY MYPI20055090A patent/MY148584A/en unknown
  • 2005-10-28 GT GT200500313A patent/GT200500313A/es unknown
  • 2005-11-03 US US11/718,665 patent/US7867499B2/en not_active Expired - Fee Related
  • 2005-11-03 EP EP05801760A patent/EP1812050A1/en not_active Withdrawn
  • 2005-11-03 CA CA002581300A patent/CA2581300A1/en not_active Abandoned
  • 2005-11-03 EP EP20100177232 patent/EP2286830A3/en not_active Withdrawn
  • 2005-11-03 BR BRPI0517682-4A patent/BRPI0517682A/pt not_active IP Right Cessation
  • 2005-11-03 MX MX2007005430A patent/MX2007005430A/es active IP Right Grant
  • 2005-11-03 AR ARP050104609A patent/AR054092A1/es unknown
  • 2005-11-03 JP JP2007536128A patent/JP2008515954A/ja not_active Withdrawn
  • 2005-11-03 SG SG200907306-5A patent/SG170646A1/en unknown
  • 2005-11-03 CN CNA2005800368845A patent/CN101048174A/zh active Pending
  • 2005-11-03 WO PCT/EP2005/011788 patent/WO2006048295A1/en not_active Ceased
  • 2005-11-03 PE PE2005001290A patent/PE20061047A1/es not_active Application Discontinuation
  • 2005-11-03 NZ NZ583688A patent/NZ583688A/en not_active IP Right Cessation
  • 2005-11-03 AU AU2005300692A patent/AU2005300692A1/en not_active Abandoned
  • 2005-11-03 RU RU2007120689/15A patent/RU2415677C2/ru not_active IP Right Cessation
  • 2005-11-03 KR KR1020077010214A patent/KR20070073882A/ko not_active Ceased
  • 2005-11-04 TW TW094138839A patent/TWI380825B/zh not_active IP Right Cessation
• 2007
  • 2007-03-22 ZA ZA200702369A patent/ZA200702369B/xx unknown
  • 2007-04-19 IL IL182692A patent/IL182692A/en not_active IP Right Cessation
  • 2007-04-24 EC EC2007007415A patent/ECSP077415A/es unknown
  • 2007-05-04 TN TNP2007000166A patent/TNSN07166A1/fr unknown
  • 2007-05-14 MA MA29899A patent/MA29020B1/fr unknown
  • 2007-05-30 NO NO20072743A patent/NO20072743L/no not_active Application Discontinuation
• 2010
  • 2010-02-04 AU AU2010200410A patent/AU2010200410B2/en not_active Ceased
  • 2010-12-17 US US12/971,534 patent/US8460676B2/en not_active Expired - Fee Related
• 2011
  • 2011-05-02 JP JP2011102847A patent/JP2011157395A/ja active Pending
• 2013
  • 2013-05-13 US US13/892,552 patent/US8617566B2/en not_active Expired - Fee Related
  • 2013-11-20 US US14/085,048 patent/US20140079730A1/en not_active Abandoned

Patent Citations (2)

Non-Patent Citations (8)

Also Published As

Similar Documents

Legal Events