This disclosure provides compounds, compositions, and methods to treat medical disorders, such as complement-mediated disorders, including complement C1s-mediated disorders.
C07D 409/14 - Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing three or more hetero rings
C07D 409/12 - Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
C07D 411/14 - Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen and sulfur atoms as the only ring hetero atoms containing three or more hetero rings
C07D 417/14 - Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group containing three or more hetero rings
The disclosure provides biomarker proteins, a change in the concentration of which are associated with neuromyelitis optica spectrum disorder (NMOSD) or clinically meaningful treatment of NMOSD with a complement component C5 inhibitor. The compositions and methods are useful for, among other things, evaluating risk for developing NMOSD, diagnosing NMOSD, monitoring progression or abatement of NMOSD, or monitoring response to treatment with a complement component C5 inhibitor.
Immunoglobulin light Chain “AL” amyloidosis is the most common form of systemic amyloidosis, accounting for approximately 70% of the diagnosed cases in developed countries. As there are treatments available, e.g., based on antibody C11-1F4, and in development for AL amyloidosis, there is a need in for more accurate methods for quality control of c11-1F4 antibodies or antigen-binding fragment thereof. Immunoassays, methods, and kits for testing the specificity of 11-1F4 antibodies are provided. The immunoassays, methods, and kits are more than 10 times more sensitive than the ELISA protocol that is routinely used for evaluation of c11-1F4 binding to LEN peptide.
A method of treating a patient with a complement-associated disorder with a complement inhibitor and then monitoring the patient during administration of the complement inhibitor and thereafter. The method includes certifying a prescriber and a dispenser and then monitoring the patient during and after administration of the complement inhibitor for an adverse event, including a meningococcal or pneumococcal event.
G16H 20/10 - 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
G16H 40/20 - ICT specially adapted for the management or administration of healthcare resources or facilitiesICT specially adapted for the management or operation of medical equipment or devices for the management or administration of healthcare resources or facilities, e.g. managing hospital staff or surgery rooms
G16H 50/20 - ICT specially adapted for medical diagnosis, medical simulation or medical data miningICT specially adapted for detecting, monitoring or modelling epidemics or pandemics for computer-aided diagnosis, e.g. based on medical expert systems
G16H 50/30 - ICT specially adapted for medical diagnosis, medical simulation or medical data miningICT specially adapted for detecting, monitoring or modelling epidemics or pandemics for calculating health indicesICT specially adapted for medical diagnosis, medical simulation or medical data miningICT specially adapted for detecting, monitoring or modelling epidemics or pandemics for individual health risk assessment
5.
TREATMENT OF MAYO STAGE IIIB LIGHT CHAIN AMYLOIDOSIS
Described herein are methods of purifying polynucleotides, e.g., imRNA and oligonucleotides, e.g., probes, primers and siRNA, using monolithic columns with immobilized ligands coupled to the monolithic column. Also described are monolithic columns for purifying polynucleotides from a sample; and methods of preparing such columns.
C12N 15/10 - Processes for the isolation, preparation or purification of DNA or RNA
B01J 20/00 - Solid sorbent compositions or filter aid compositionsSorbents for chromatographyProcesses for preparing, regenerating or reactivating thereof
C12Q 1/6806 - Preparing nucleic acids for analysis, e.g. for polymerase chain reaction [PCR] assay
7.
DOSAGE AND ADMINISTRATION OF ANTI-C5 ANTIBODIES FOR TREATING IGA NEPHROPATHY (IGAN)
Compositions and methods are provided that are useful for treating or preventing cytokine release syndrome, which is a major cause of deaths in infections with virulent viruses such as the coronaviruses and influenza viruses. Therapies such as immunomodulators and CAR-T have also been associated with cytokine release syndrome. The treatment includes the administration of a SYK inhibitor or a pharmaceutically acceptable salt thereof. preferably a dual SYK/JAK inhibitor or a pharmaceutically acceptable salt thereof.
Compositions and methods for treating lymphoma, in particular. T-cell lymphoma and follicular lymphoma. in a human patient are provided. The methods entail administering to the patient an effective amount of cerdulatinib.
A61K 31/5377 - 1,4-Oxazines, e.g. morpholine not condensed and containing further heterocyclic rings, e.g. timolol
A61K 31/635 - Compounds containing para-N-benzene- sulfonyl-N-groups, e.g. sulfanilamide, p-nitrobenzenesulfonohydrazide having a heterocyclic ring, e.g. sulfadiazine
A61K 39/00 - Medicinal preparations containing antigens or antibodies
A61K 39/395 - AntibodiesImmunoglobulinsImmune serum, e.g. antilymphocytic serum
A61P 35/02 - Antineoplastic agents specific for leukemia
Provided are agents and methods for the detection of complement-mediated thrombotic microangiopathy (CM-TMA) biomarkers. The agents may specifically bind to CM-TMA biomarkers, preferably a proteolytic fragment of complement component factor B (Ba) and soluble C5b9 (sC5b9) and can be used in methods of diagnosis and treatment of CM-TMA, e.g., treatment with an anti-C5 antibody such as ravulizumab (ALXN1210).
The present invention relates unit dose formulations of antidotes to anticoagulants targeting factor Xa. Disclosed herein are methods of stopping or preventing bleeding in a patient that is currently undergoing anticoagulant therapy with a factor Xa inhibitor.
05 - Pharmaceutical, veterinary and sanitary products
Goods & Services
Pharmaceutical preparations for use in oncology; Pharmaceutical preparations for the treatment of diseases and disorders of the cardiovascular, renal, metabolic, respiratory, nervous, dermatological, neurological, gastrointestinal, and immune systems; Pharmaceutical preparations for the treatment of infection, inflammation, hematological, and autoimmune related diseases and disorders; Antibodies for medical purposes; Vaccines
05 - Pharmaceutical, veterinary and sanitary products
Goods & Services
Pharmaceutical preparations for use in oncology; Pharmaceutical preparations for the treatment of infection, inflammation, hematological, and autoimmune related diseases and disorders; Antibodies for medical purposes; Vaccines; Pharmaceutical preparations for the treatment of diseases and disorders of the cardiovascular, renal, metabolic, respiratory, nervous, dermatological, neurological, gastrointestinal, and immune systems
05 - Pharmaceutical, veterinary and sanitary products
Goods & Services
Pharmaceutical preparations for use in oncology; Pharmaceutical preparations for the treatment of infection, inflammation, hematological, and autoimmune related diseases and disorders; Antibodies for medical purposes; Vaccines; Pharmaceutical preparations for the treatment of diseases and disorders of the cardiovascular, renal, metabolic, respiratory, nervous, dermatological, neurological, gastrointestinal, and immune systems
The present disclosure relates to solutions and methods of preparing lyophilized formulations of factor Xa (fXa) antidotes. A suitable aqueous formulation suitable for lyophilization can include a fXa antidote, a solubilizing agent, a stabilizer, and a crystalline component, wherein the formulation does not collapse during lyophilization.
The disclosure provides engineered polypeptides that specifically bind to human complement component C5 and/or serum albumin. The disclosure also provides fusion proteins comprising such engineered polypeptides, wherein such fusion proteins may be multivalent and multi-specific fusion proteins. The disclosure further provides nucleic acid molecules that encode such engineered polypeptides or fusion proteins, and methods of making such engineered polypeptides or fusion proteins. The disclosure further provides pharmaceutical compositions that comprise such engineered polypeptides or fusion proteins, and methods of treatment using such engineered polypeptides or fusion proteins.
Provided herein are anti-transthyretin (TTR) antibodies, corresponding polynucleotides and expression vectors as well as compositions (e.g., pharmaceutical compositions) and related articles of manufacture that contain the anti-TTR antibody as a drug. Provided herein are also methods of treating or preventing transthyretin-mediated amyloidosis (ATTR) in a subject in need thereof using the pharmaceutical compositions. Additionally, provided herein are methods for validating, identifying, and screening of an amyloid depleting drug using high-resolution live-cell imaging as well as methods for producing a pharmaceutical composition of an amyloid depleting drug and kits suitable for use in said methods.
The disclosure provides methods of treating myasthenia gravis (MG) in a subject in need thereof by administering to the subject a substance that specifically binds complement component 5 (C5). In certain embodiments, the substance that specifically binds C5 is a binding protein, such as an anti-C5 antibody.
The present disclosure relates to stable aqueous solutions comprising a high concentration of an anti-C5 antibody (e.g., ravulizumab) and methods for preparing the solutions. The disclosure also provides methods for treating or preventing complement-associated disorders, such as paroxysmal nocturnal hemoglobinuria (PNH) and atypical hemolytic uremic syndrome (aHUS), using the solutions. Also featured were therapeutic kits containing one or more of the solutions and a means for administering the solutions to a patient in need such a treatment.
Provided are methods for clinical treatment of Paroxysmal Nocturnal Hemoglobinuria (PNH) comprising administering to the patient an anti-C5 antibody, or antigen binding fragment thereof, wherein the anti-C5 antibody, or antigen binding fragment thereof, is administered (or is for administration) subcutaneously according to a particular clinical dosage regimen (i.e., at a particular dose amount and according to a specific dosing schedule). In one embodiment, the patient has previously been treated with eculizumab (Soliris®).
The disclosure provides antibodies that are useful for, among other things, inhibiting terminal complement (e.g., the assembly and/or activity of the C5b-9 TCC) and C5a anaphylatoxin-mediated inflammation and, thus, treating complement-associated disorders. The antibodies have a number of improved properties relative to eculizumab, including, e.g., increased serum half-life in a human.
A61K 39/00 - Medicinal preparations containing antigens or antibodies
C07K 16/28 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
C07K 16/40 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against enzymes
24.
DOSAGE AND ADMINISTRATION OF ANTI-C5 ANTIBODIES FOR TREATMENT OF PAROXYSMAL NOCTURNAL HEMOGLOBINURIA (PNH) AND ATYPICAL HEMOLYTIC UREMIC SYNDROME (AHUS)
Provided are methods for clinical treatment of Paroxysmal Nocturnal Hemoglobinuria (PNH) and Atypical Hemolytic Uremic Syndrome (aHUS) using an anti-C5 antibody, or antigen binding fragment thereof.
A61K 39/395 - AntibodiesImmunoglobulinsImmune serum, e.g. antilymphocytic serum
A61K 9/00 - Medicinal preparations characterised by special physical form
A61K 39/00 - Medicinal preparations containing antigens or antibodies
A61P 7/00 - Drugs for disorders of the blood or the extracellular fluid
C07K 16/18 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans
25.
DOSAGE AND ADMINISTRATION OF ANTI-C5 ANTIBODIES FOR TREATMENT OF PAROXYSMAL NOCTURNAL HEMOGLOBINURIA (PNH) AND ATYPICAL HEMOLYTIC UREMIC SYNDROME (AHUS)
Provided are methods for clinical treatment of Paroxysmal Nocturnal Hemoglobinuria (PNH) and Atypical Hemolytic Uremic Syndrome (aHUS) using an anti-C5 antibody, or antigen binding fragment thereof.
The present disclosure relates to compositions and methods useful for improving the hemostatic efficacy in a patient having suffered from intracranial hemorrhage while undergoing an anticoagulation treatment with a factor Xa (FXa) inhibitor. In some embodiments, the patient is selected if the patient exhibits high hematoma growth rate and/or high diastolic blood pressure.
The present disclosure relates to, inter alia, compositions containing an inhibitor of human complement and use of the compositions in methods for treating or preventing complement-associated disorders. In some embodiments, the inhibitor is chronically administered to patients. In some embodiments, the inhibitor is administered to a patient in an amount and with a frequency to maintain systemic complement inhibition and prevent breakthrough. In some embodiments, the compositions contain an antibody, or antigen-binding fragment thereof, that binds to a human complement component C5 protein or a fragment of the protein such as C5a or C5b.
Disclosed herein are methods for treating lupus nephritis (LN) and/or immunoglobulin A (IgA) nephropathy in a subject. The methods include administering to the subject a therapeutically effective amount of a small molecule complement factor D inhibitor.
A61K 31/506 - PyrimidinesHydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
A61K 31/5377 - 1,4-Oxazines, e.g. morpholine not condensed and containing further heterocyclic rings, e.g. timolol
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 to antidotes to anticoagulants targeting factor Xa. The antidotes are factor Xa protein derivatives that bind to the factor Xa inhibitors thereby substantially neutralizing them but do not assemble into the prothrombinase complex. In one embodiment, the derivatives described herein lack or have reduced intrinsic coagulant activity.
This disclosure relates to methods of treating a copper metabolism-associated disease or disorder, such as Wilson disease (WD). This disclosure also relates to methods of sequestering copper in a subject or of mobilizing copper into plasma in a subject.
C07D 207/08 - Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon radicals, substituted by hetero atoms, attached to ring carbon atoms
C07D 401/14 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
The disclosure features methods for treating neutralizing antibodies that reduce the efficacy of soluble alkaline phosphatase treatment (e.g., asfotase alfa), an enzyme replacement therapy, such as for the treatment of bone mineralization disorders, e.g., hypophosphatasia (HPP). The methods include diagnosing a subject as having the presence of neutralizing antibodies that affect the efficacy of treatment, administering a treatment suitable for reducing the deleterious effects of neutralizing antibodies, and continuing alkaline phosphatase treatment.
The present disclosure provides methods for the synthesis of complement factor D inhibitors and intermediates thereof. The methods involve subjecting an intermediate in the synthesis of a complement factor D inhibitor to a t-butyl ester deprotection reaction using a weak base.
C07D 403/04 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group containing two hetero rings directly linked by a ring-member-to-ring- member bond
34.
METHODS FOR TREATING LYSOSOMAL ACID LIPASE DEFICIENCY IN PATIENTS
The present invention provides methods of treating LAL deficiency comprising administering to a mammal a therapeutically effective amount of lysosomal acid lipase with an effective dosage frequency. Methods of improving growth and liver function, increasing LAL tissue concentration, and increasing LAL activity in a human patient suffering from LAL deficiency are also provided.
C07D 401/14 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
C07D 405/14 - Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing three or more hetero rings
C07D 209/14 - Radicals substituted by nitrogen atoms, not forming part of a nitro radical
36.
ALKALINE PHOSPHATASE POLYPEPTIDES AND METHODS OF USE THEREOF
Featured are pharmaceutical compositions that include a soluble alkaline phosphatase for treating bone mineralization disorders, such as hypophosphatasia (HPP), and symptoms thereof. The polypeptides include a soluble alkaline phosphatase (sALP) or fragment thereof, which is derived from a naturally occurring alkaline phosphatase (ALP).
A method of measuring endothelial cell specific complement activation is provided. The method can comprise screening a test compound for complement modulation. The methods and assays of the present disclosure can be used to monitor response to treatment of a complement-mediated disease with a complement modulator. The present disclosure further relates to idiopathic inflammatory myopathies and other diseases associated with aberrant activation of one of more complement system in endothelial cells, for example, with respect to dermatomyositis (DM) and complement-mediated thrombotic microangiopathy (CM-TMA), both of which can manifest with autoimmune syndromes such as lupus.
Disclosed herein are methods of detecting complement activity in a biological sample. The disclosure also relates to methods for diagnosis or prognostic assessment of a complement-mediated disease in a subject and methods for monitoring response to treatment of a complement-mediated disease with a complement modulator in a subject.
Provided are devices, systems, and methods for clinical treatment of complement disorders (e.g., paroxysmal nocturnal hemoglobinuria and atypical hemolytic uremic syndrome) in a pediatric human patient using subcutaneous delivery systems (e.g., on-body device and/or syringe) to administer an effective amount of a therapeutic anti-C5 antibody such as ravulizumab, or antigen-binding fragment thereof.
Methods and assays are provided for high-throughput ranking of antigen binding by generating and testing of antibody fragments from full‑length antibodies.
C40B 30/04 - Methods of screening libraries by measuring the ability to specifically bind a target molecule, e.g. antibody-antigen binding, receptor-ligand binding
Methods, systems, and computer readable media for determining the efficacy of paroxysmal nocturnal hemoglobinuria (PNH) treatment in improving quality of life (QoL). In aspects, the system uses electronically collected patient reported outcomes (ePROs) and passive health data from a wearable device in order to determine the QoL of a patient being treated for PNH compared to global QoL averages.
G16H 10/20 - ICT specially adapted for the handling or processing of patient-related medical or healthcare data for electronic clinical trials or questionnaires
G16H 20/10 - 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
G16H 50/30 - ICT specially adapted for medical diagnosis, medical simulation or medical data miningICT specially adapted for detecting, monitoring or modelling epidemics or pandemics for calculating health indicesICT specially adapted for medical diagnosis, medical simulation or medical data miningICT specially adapted for detecting, monitoring or modelling epidemics or pandemics for individual health risk assessment
G16H 50/20 - ICT specially adapted for medical diagnosis, medical simulation or medical data miningICT specially adapted for detecting, monitoring or modelling epidemics or pandemics for computer-aided diagnosis, e.g. based on medical expert systems
43.
ASSAY METHODS FOR SCREENING INHIBITORS OF SICKLE CELL DISEASE, ß-THALASSEMIA, OR SICKLE CELL ß-THALASSEMIA, OR A PHENOTYPE THEREOF
The present disclosure is directed to methods of identifying a test compounds for treating sickle cell disease (SCD), β-thalassemia (BT), or sickle cell BT. The methods involved contacting a test sample including cells with heme, serum, and a test compound, and measuring a biological phenomena including (1) deposition of a complement factor on the cells in the test sample; or (2) effect(s) of the complement factor deposition of (1) on target effector cells, where an attenuation in the biological phenomena in the test sample compared to the biological phenomena in a reference standard is indicative that the test compound is effective in treating sickle cell disease (SCD), -thalassemia (BT), or sickle cell BT.
Disclosed are methods of treating a copper metabolism-associated disease or disorder, such as Wilson disease (WD) in a subject, particularly in a subject who is from about 3 years old to less than about 18 years old. Also disclosed are compositions comprising bis-choline tetrathiomolybdate for use in the treatment of a copper metabolism-associated disease or disorder, such as Wilson disease (WD) in a subject, particularly in a subject who is from about 3 years old to less than about 18 years old. Also disclosed are uses of a composition comprising bis-choline tetrathiomolybdate for the manufacture of a medicament for treating a copper metabolism-associated disease or disorder, such as Wilson disease (WD) in a subject, particularly in a subject who is from about 3 years old to less than about 18 years old.
The present disclosure relates to methods, uses, and compositions for the treatment of Sickle cell disease (SCD), beta thalassemia (BT), or sickle cell BT. More specifically, the disclosure concerns the treatment of patients having SCD. BT, or sickle cell BT using a complement C5 inhibitor, such as an anti-C5 antibody or fragment thereof, a nucleic acid molecule, a peptide, a small molecule, or an aptamer.
The present invention relates to methods, uses, and compositions for the treatment of Sickle cell disease (SCD), beta thalassemia (BT), sickle cell BT. More specifically, the invention concerns the treatment of patients having SCD, BT, or sickle cell BT using a complement pathway component (e.g., Factor P (properdin)) inhibitor, such as an antibody or fragment thereof, a nucleic acid molecule, a peptide, a small molecule, or an aptamer, among others.
This present disclosure features solid dispersion and liquid gelatin capsule formulations of danicopan that can improve the oral bioavailability and/or shelf stability of danicopan. The present disclosure also features methods for treating complement factor D mediated disorders, including paroxysmal nocturnal hemoglobinuria (PNH), e.g., PNH with clinically evident extravascular hemolysis (EVH), and geographic atrophy (GA) secondary to age-related macular degeneration (AMD) using the formulations.
Methods, systems, and computer readable media for identifying a patient cohort of patients that have atypical hemolytic uremic syndrome (aHUS) are provided. In aspects, diagnostic records and claims data are used to determine a subset of patients that may be used to train a machine learning model that may predict, based on a patient's claims data, the patient's aHUS diagnosis.
G16H 50/20 - ICT specially adapted for medical diagnosis, medical simulation or medical data miningICT specially adapted for detecting, monitoring or modelling epidemics or pandemics for computer-aided diagnosis, e.g. based on medical expert systems
A61B 5/00 - Measuring for diagnostic purposes Identification of persons
G16H 50/70 - ICT specially adapted for medical diagnosis, medical simulation or medical data miningICT specially adapted for detecting, monitoring or modelling epidemics or pandemics for mining of medical data, e.g. analysing previous cases of other patients
G16H 70/60 - ICT specially adapted for the handling or processing of medical references relating to pathologies
49.
COMPOSITIONS AND METHODS FOR INCREASING THE SERUM HALF-LIFE OF A THERAPEUTIC AGENT TARGETING COMPLEMENT C5
The disclosure features compositions and methods for increasing the half-life of a therapeutic agent (e.g., a C5 antagonist) in the serum of a subject (e.g., a human). Also featured are compositions and methods for: (i) decreasing the frequency by which a therapeutically effective amount of a therapeutic agent must be administered to a human having, suspected of having, or at risk for developing, a medical condition for which the therapeutic agent is effective and (ii) decreasing the dosage of the therapeutic agent required for therapeutic efficacy in a human having, suspected of having, or at risk for developing, a medical condition for which the therapeutic agent is effective. The methods include reducing the serum concentration of the antigen to which the therapeutic agent binds.
A61K 39/395 - AntibodiesImmunoglobulinsImmune serum, e.g. antilymphocytic serum
A61K 31/7105 - Natural ribonucleic acids, i.e. containing only riboses attached to adenine, guanine, cytosine or uracil and having 3'-5' phosphodiester links
A61K 39/00 - Medicinal preparations containing antigens or antibodies
C07K 16/18 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans
C12N 15/113 - Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides
50.
DOSAGE AND ADMINISTRATION OF ANTI-C5 ANTIBODIES FOR TREATING DERMATOMYOSITIS (DM)
Provided are dosages and methods for clinical treatment of dermatomyositis (DM), particularly severe and/or refractory DM, in human patients using an anti C5 antibody, or antigen binding fragment thereof (e.g., such as ravulizumab (ULTOMIRIS®)).
A61P 21/00 - Drugs for disorders of the muscular or neuromuscular system
C07K 16/28 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
51.
KIDNEY ACTIVE FUSION PROTEINS AND METHODS OF TREATMENT USING THE SAME
Described herein are fusion proteins which include factor H catalytic domains and may include VHH domains, factor H-related protein 5 domains, or integrin binding domains, and the use of such fusion proteins in methods of treatment of diseases mediated by complement alternative pathway activation or dysregulation, for example, kidney diseases.
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
Described herein are fusion proteins that include a fragment of factor H and an Fc receptor binding domain, as well as the use of such proteins in methods of treatment for diseases mediated by alternative complement pathway dysregulation.
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
Disclosed herein are methods for treating geographic atrophy secondary to age-related macular degeneration (AMD) and intermediate AMD in a subject. The methods include administering to the subject a therapeutically effective amount of a small molecule complement factor D inhibitor.
Disclosed herein are methods for treating myasthenia gravis (MG) in a subject. The methods include administering to the subject a therapeutically effective amount of a small molecule complement factor D inhibitor.
Provided are methods for clinical treatment of hematopoietic stem cell transplant-associated thrombotic microangiopathy (HSCT-TMA), e.g., TMA after HSCT, in human patients using an anti-C5 antibody, or antigen binding fragment thereof.
C07D 213/02 - Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
C07D 213/04 - Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
C07D 213/60 - Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
C07D 213/73 - Unsubstituted amino or imino radicals
60.
UNIT DOSE FORMULATION OF ANTIDOTES FOR FACTOR XA INHIBITORS AND METHODS OF USING THE SAME
The present invention relates unit dose formulations of antidotes to anticoagulants targeting factor Xa. Disclosed herein are methods of stopping or preventing bleeding in a patient that is currently undergoing anticoagulant therapy with a factor Xa inhibitor.
Methods and compositions TACI-Fc fusion proteins binding to and inhibiting the activity of BAFF, APRIL ligands to neutralize their activity and block or antagonize the activity of their corresponding B cell stimulatory receptors are provided. The TACI-Fc fusion proteins include a mutant Fc domain designed to mitigate one or more effector functions, such as complement-dependent cytotoxicity (CDC) and antibody-dependent cell cytotoxicity (ADCC), and inhibit IgG recycling by neonatal Fc receptor (FcRn) blockade. The TACI-Fc fusion proteins can be used for the treatment of a variety of maladies, including diseases, disorders and conditions associated with a dysregulated immune response associated with inflammatory or autoimmune symptoms.
This disclosure relates to compounds, pharmaceutical compositions comprising them, and methods of using the compounds and compositions for treating diseases or disorders related to misregulation of the Complement cascade pathway. More particularly, this disclosure relates to macrocyclic compounds and pharmaceutical compositions thereof, methods of inhibiting Complement Factor B (CFB) expression with these compounds, and methods of treating diseases or disorders mediated by CFB.
A61K 31/437 - 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 five-membered ring having nitrogen as a ring hetero atom, e.g. indolizine, beta-carboline
A61K 31/675 - Phosphorus compounds having nitrogen as a ring hetero atom, e.g. pyridoxal phosphate
C07D 401/06 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
C07D 491/044 - Ortho-condensed systems with only one oxygen atom as ring hetero atom in the oxygen-containing ring
C07D 491/056 - Ortho-condensed systems with two or more oxygen atoms as ring hetero atoms in the oxygen-containing ring
C07D 491/147 - Ortho-condensed systems the condensed system containing one ring with oxygen as ring hetero atom and two rings with nitrogen as ring hetero atom
Provided herein are anti-TTR antibody dosing regimens useful for treatment of transthyretin amyloid cardiomyopathy (ATTR-CM) in an adult human patient. In embodiments, the patient is treated with an anti-TTR antibody comprising NI006/ALXN2220.
C07K 16/18 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans
A61K 39/395 - AntibodiesImmunoglobulinsImmune serum, e.g. antilymphocytic serum
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
64.
ANTI-C5 ANTIBODIES HAVING IMPROVED PHARMACOKINETICS
The disclosure provides antibodies that are useful for, among other things, inhibiting terminal complement (e.g., the assembly and/or activity of the C5b-9 TCC) and C5a anaphylatoxin-mediated inflammation and, thus, treating complement-associated disorders. The antibodies have a number of improved properties relative to eculizumab, including, e.g., increased serum half-life in a human.
C07K 16/28 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
C07K 16/40 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against enzymes
05 - Pharmaceutical, veterinary and sanitary products
Goods & Services
Pharmaceutical preparations and substances for the treatment of complement-medicated diseases and disorders
70.
DOSAGE AND ADMINISTRATION OF ANTI-C5 ANTIBODIES FOR PREVENTING OR MINIMIZING CARDIAC SURGERY ASSOCIATED ACUTE KIDNEY INJURY (CSA-AKI) AND/OR SUBSEQUENT MAJOR ADVERSE KIDNEY EVENTS (MAKE) IN PATIENTS WITH CHRONIC KIDNEY DISEASE
e.ge.ge.g.e.g., ravulizumab or eculizumab, or antigen binding fragments thereof, according to a particular clinical dosage regimen and according to a specific schedule.
This disclosure relates to novel formulations of bis-choline tetrathiomolybdate useful for treating a copper metabolism-associated disease or disorder, such as Wilson disease (WD). For example, this disclosure relates to low dose formulations of bis-choline tetrathiomolybdate.
Provided are methods for clinical treatment of complement-mediated TMA (CM-TMA) (e.g., CM-TMA associated with a trigger, such as autoimmune condition, an infection, a transplant, one or more drugs, or malignant hypertension), using an anti-C5 antibody, or antigen binding fragment thereof, such as ravulizumab (ULTOMIRIS®).
e.g.e.ge.g., blood or plasma sample) from the patient, (2) determining or having determined elevated TM and SYND1 levels in the sample compared to normal reference ranges of TM and SYND1, respectively, and (3) administering to the patient an anti-C5 antibody or an anti-CFB antibody in an amount and with a frequency sufficient to treat HSCT-TMA after elevated TM and SYND1 levels have been determined. In one embodiment, the methods further comprise determining or having determined elevated Ba levels in the sample compared to a normal reference range for Ba. In another embodiment, the methods further comprise determining or having determined an elevated HSPG level in the sample compared to a normal reference range for HSPG. Further provided are methods of identifying a patient having HSCT-TMA that is suitable for treatment with an anti-C5 antibody or an anti-CFB antibody, as well as methods for monitoring responsiveness of a patient having HSCT-TMA to treatment with an anti-C5 antibody or an anti-CFB antibody.
The present invention relates antidotes to anticoagulants targeting factor Xa. The antidoes are factor Xa protein derivatives that bind to the factor Xa inhibitors thereby substantially neutralizing them but do not assemble into the prothrombinase complex. The derivatives describe herein lack or have reduced intrinsic coagulant activity. Disclosed herein are methods of stopping or preventing bleeding in a patient that is currently undergoing anticoagulant therapy with a factor Xa inhibitor.
A61K 38/48 - Hydrolases (3) acting on peptide bonds (3.4)
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
C07K 14/435 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from animalsPeptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from humans
C12N 9/64 - Proteinases derived from animal tissue, e.g. rennin
The present disclosure provides methods for manufacturing a fXa derivative protein at large scale leading to high yield of highly pure protein product. The method may include adding a detergent to a sample that contains a polynucleotide construct encoding the protein and purifying the protein through a soybean trypsin inhibitor (STI)-based affinity chromatograph, an ion exchange and mixed mode chromatograph and a hydrophobic interaction.
The disclosure provides methods for treating a human patient with sickle cell disease. These methods include administering a properdin binding antibody or antigen-binding fragment thereof to the patient.
This disclosure provides peptide based compounds, compositions, and methods to treat medical disordeds, such as complement-mediated disorders, including complement C1s-mediated disorders, such as acute antibody-mediated rejection, amyotrophic lateral sclerosis, autoimmune blistering disease, bullous pemphigoid, geographic atrophy, or Guillain-Barre Syndrome, comprising administering to a subject in need thereof a therapeutically effective amount of the compound.
C07D 207/08 - Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon radicals, substituted by hetero atoms, attached to ring carbon atoms
C07K 5/078 - Dipeptides the first amino acid being heterocyclic, e.g. Pro, His, Trp
C07K 5/097 - Tripeptides the first amino acid being heterocyclic, e.g. Pro, His, Trp, e.g. thyroliberin, melanostatin
80.
PHARMACEUTICAL COMPOUNDS FOR THE TREATMENT OF COMPLEMENT MEDIATED DISORDERS
This disclosure provides compounds, compositions, and methods to treat medical disorders, such as complement-mediated disorders, including complement C1s-mediated disorders.
Featured are methods of manufacturing recombinant alkaline phosphatases, such as asfotase alfa, that provide more precise quality control over total sialic acid content (TSAC) concentration in the final product by measuring TSAC concentration during fermentation and adjusting downstream production steps in response.
Provided herein are antibodies which bind to ceruloplasmin and are useful for various applications, including detecting ceruloplasmin and immunocapturing ceruloplasmin in biological samples. The antibodies are useful in methods of measuring non-ceruloplasmin-bound copper concentrations and labile-bound copper concentrations in biological samples.
The present disclosure provides pharmaceutical compositions formulated for high concentrations of fusion proteins for subcutaneous administration and methods of use thereof. Furthermore, the disclosure provides methods of developing high concentration protein formulations.
The disclosure provides antibody immune cell inhibitor fusion proteins comprising four polypeptide chains that form two antigen binding sites and at least two immune cell receptor binding sites that inhibit or diminish activation of an immune effector cell when bound to a target antigen. The disclosure also provides antibody immune cell inhibitor fusion proteins comprising two polypeptide chains that form one antigen binding site and at least one immune cell receptor binding site that inhibit or diminish activation of an immune effector cell when bound to a target antigen. The disclosure further provides pharmaceutical compositions and kits that comprise such antibody immune cell inhibitor fusion proteins, and methods of treatment using such proteins.
The disclosure provides a method of reducing the likelihood of forming a T cell-mediated allograft vasculopathy lesion in a mammalian transplant recipient comprising transplanting an allograft from a donor to a recipient and administering a therapeutically effective amount of an anti-C5 antibody, or antigen-binding fragment thereof, to the recipient, wherein the anti-C5 antibody, or antigen-binding fragment thereof reduces the likelihood of forming an allograft vasculopathy lesion in the allograft, compared to the absence of treatment with an anti-C5 antibody, or antigen-binding fragment thereof.
A61K 39/395 - AntibodiesImmunoglobulinsImmune serum, e.g. antilymphocytic serum
C07K 16/18 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans
A61P 9/00 - Drugs for disorders of the cardiovascular system
A61P 37/06 - Immunosuppressants, e.g. drugs for graft rejection
C07K 16/28 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
C07K 16/40 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against enzymes
86.
ADMINISTRATION OF ANTI-C5 ANTIBODIES FOR TREATMENT OF PATIENTS WITH MEMBRANOPROLIFERATIVE GLOMERULONEPHRITIS
Provided are methods for clinical treatment of Membranoproliferative glomerulonephritis (MPGN) by administering an anti-C5 antibody, or antigen binding fragment thereof.
Provided herein are methods of treatment designed to prevent or minimize formation of deleterious multivalent immune complexes in a human patient having a complement mediated disorder (e.g., paroxysmal nocturnal hemoglobinuria (PNH) or atypical hemolytic uremic syndrome (aHUS)), who has been or is being treated with a first anti-C5 antibody and is then treated with a second (different) anti-C5 antibody, as well as methods of safely switching a patient from treatment with a first anti-C5 antibody to a second (different) anti-C5 antibody. Also provided are methods for determining an adjusted regimen antibody (e.g., a regimen to prevent or minimize formation of multivalent immune complexes) comprising an adjusted therapeutic dose and/or timing of administration of a second anti-C5 to treat a patient who has been or is being treated with a first anti-C5 antibody.
The present disclosure relates to, inter alia, a method of treating a complement mediated disorder caused by a virus, e.g., corona virus; Dengue virus (DENY); Ross River vims (RRV) and/or influenza virus (flu) by administering an effective amount of a complement modulator, such as, e.g., C5 inhibitor, such as eculizumab or an eculizumab variant or a C5a inhibitor such as olendalizumab (ALXN1007) or a variant thereof, to the subject. In addition, the present disclosure relates to, inter alia, a method of treating human patients inflicted with severe coronavirus disease-2019 (severe COVID-19) who is undergoing treatment with eculizumab. The method includes measuring a level of circulating component C5b-9 (membrane attack complex), in the patient's blood sample to titrate an effective eculizumab dose for the treatment of COVID-19.
Disclosed are methods and isolated cells useful for the improved production of function fXa derivative protein that acts as a fXa inhibitor antidote. One aspect relates to an isolated cell comprising the r-Antidote polynucleotide and Furin polynucleotide. Another aspect relates to a method for preparing the cleaved two-chain r-Antidote by expressing, in a cell, the pre-processed r-Antidote polypeptide and a Furin polypeptide.
Featured are compositions and methods for treating bone mineralization disorders, such as hypophosphatasia (HPP). In some embodiments, the methods described herein are useful for treating adult subjects with HPP and/or treating or preventing bone fractures.
Immunoglobulin light Chain "AL" amyloidosis is the most common form of systemic amyloidosis, accounting for approximately 70% of the diagnosed cases in developed countries. As there are treatments available, e.g., based on antibody C11-1F4, and in development for AL amyloidosis, there is a need in for more accurate methods for quality control of c11-1F4 antibodies or antigen-binding fragment thereof. Immunoassays, methods, and kits for testing the specificity of 11-1F4 antibodies are provided. The immunoassays, methods, and kits are more than 10 times more sensitive than the ELISA protocol that is routinely used for evaluation of c11-1F4 binding to LEN peptide.
G01N 33/532 - Production of labelled immunochemicals
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
G01N 33/543 - ImmunoassayBiospecific binding assayMaterials therefor with an insoluble carrier for immobilising immunochemicals
G01N 33/68 - Chemical analysis of biological material, e.g. blood, urineTesting involving biospecific ligand binding methodsImmunological testing involving proteins, peptides or amino acids
The disclosure provides methods of treating a subject having or suspected of having dermatomyositis using a composition including a bi-specific fusion protein. The composition may be administered using a medical device, such as a wearable injector.
Provided are methods for clinical treatment of neuromyelitis optica spectrum disorder (NMOSD) using an anti-C5 antibody, or antigen binding fragment thereof.
METHOD OF USING EXTRACELLULAR VESICLES TO DETECT COMPLEMENT ACTIVATION, AND USES THEREOF TO ASSESS AND/OR MONITOR TREATMENT OF A COMPLEMENT-MEDIATED DISEASE
Disclosed herein are methods of detecting complement activity in a biological sample. The disclosure also relates to methods for diagnosis or prognostic assessment of a complement-mediated disease in a subject and methods for monitoring response to treatment of a complement-mediated disease with a complement modulator in a subject.
G01N 33/68 - Chemical analysis of biological material, e.g. blood, urineTesting involving biospecific ligand binding methodsImmunological testing involving proteins, peptides or amino acids
97.
DOSAGE AND ADMINISTRATION OF ANTI-C5 ANTIBODIES FOR TREATING C5-MEDIATED GLOMERULAR NEPHRITIS (GN), INCLUDING LUPUS NEPHRITIS (LN) AND/OR IGA NEPHROPATHY (IGAN)
Provided are dosages and methods for clinical treatment of C5-mediated glomerular nephritis (GN), including lupus nephritis (LN) and immunoglobulin A nephropathy (IgAN), in human patients using an anti C5 antibody, or antigen binding fragment thereof (e.g., such as ravulizumab (ULTOMIRIS®)), optionally together with background therapy for treating LN (e.g., an immuno-suppressant) or background therapy for treating IgAN (e.g., renin-angiotensin system (RAS) inhibiting medication).
The present disclosure provides methods and compositions useful for diagnosing and treating activated alternative pathway of complement in a human subject with a SARS-CoV-2 infection. Also provided are methods of treating an infection by a betacoronavirus, e.g., SARS-CoV, MERS-CoV, or SARS-CoV-2, in a human subject. The methods of treatment include administering to the human subject a therapeutically effective amount of at least one complement factor D inhibitor. Also provided herein are compounds for treating an infection by a betacoronavirus and their use in the manufacture in a medicament for treating an infection by a betacoronavirus.
Compositions and methods are provided that are useful for treating or preventing cytokine release syndrome, which is a major cause of deaths in infections with virulent viruses such as the coronaviruses and influenza viruses. Therapies such as immunomodulators and CAR-T have also been associated with cytokine release syndrome. The treatment includes the administration of a SYK inhibitor or a pharmaceutically acceptable salt thereof, preferably a dual SYK/JAK inhibitor or a pharmaceutically acceptable salt thereof.
A61K 31/495 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two nitrogen atoms as the only ring hetero atoms, e.g. piperazine
A61K 31/395 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
A61K 31/505 - PyrimidinesHydrogenated pyrimidines, e.g. trimethoprim
