The present disclosure provides binding proteins (e.g., antibodies or antigen binding fragments thereof) that specifically bind to Klebsiella pneumoniae 02 and induce opsonophagocytic killing of Klebsiella (e.g., Klebsiella pneumoniae) and/or protects mice from a lethal Klebsiella challenge. The present disclosure also provides methods of reducing Klebsiella (e.g., Klebsiella pneumoniae) or treating or preventing Klebsiella (e.g., Klebsiella pneumoniae) infection in a subject comprising administering the Klebsiella pneumoniae 02 binding proteins, (e.g., antibodies or antigen-binding fragments thereof) to the subject.
C07K 16/12 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from bacteria
A61K 31/407 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil condensed with heterocyclic ring systems, e.g. ketorolac, physostigmine
A61K 39/00 - Medicinal preparations containing antigens or antibodies
A61K 39/40 - AntibodiesImmunoglobulinsImmune serum, e.g. antilymphocytic serum bacterial
This invention relates to methods of lowering plasma levels of endothelial lipase (EL) in patients in need thereof comprising administering MEDI5884 to subjects at a dose of from about 50 mg to about 600 mg per month.
C07K 16/40 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against enzymes
A61K 39/00 - Medicinal preparations containing antigens or antibodies
A61P 9/10 - Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
3.
TREATMENT OF EOSINOPHILIC ESOPHAGITIS WITH ANTI-TSLP ANTIBODY
The present disclosure, relates, in general, to methods of treating eosinophilic esophagitis (EOE) using an antibody specific for thymic stromal lymphopoietin (TSLP).
C07K 16/24 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against cytokines, lymphokines or interferons
4.
TREATMENT OF EOSINOPHILIC ESOPHAGITIS WITH ANTI-TSLP ANTIBODY
The present disclosure, relates, in general, to methods of treating eosinophilic esophagitis (EOE) using an antibody specific for thymic stromal lymphopoietin (TSLP).
C07K 16/24 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against cytokines, lymphokines or interferons
A61K 39/00 - Medicinal preparations containing antigens or antibodies
5.
DECREASING STAPHYLOCOCCUS AUREUS INFECTIONS IN COLONIZED PATIENTS
The present disclosure is directed to methods of treating subjects colonized with S. aureus with an anti-alpha toxin antibody or antigen-binding fragment thereof. The methods can decrease the incidence of infection attendant to the presence of S. aureus in the subject.
C12Q 1/689 - Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for detection or identification of organisms for bacteria
Provided herein are methods for treating, reducing or preventing influenza A virus infection in a patient, as well as compositions and articles of manufacture for treating, reducing or preventing influenza A virus infection in a patient.
A61K 31/215 - Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids
A61K 31/7012 - Compounds having a free or esterified carboxyl group attached, directly or through a carbon chain, to a carbon atom of the saccharide radical, e.g. glucuronic acid, neuraminic acid
A61K 39/00 - Medicinal preparations containing antigens or antibodies
A61P 31/16 - Antivirals for RNA viruses for influenza or rhinoviruses
C07K 16/10 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from viruses from RNA viruses
The disclosure relates to an antibody of the class IgG4 comprising two heavy chains, wherein each of the heavy chains comprises a human IgG4 constant region comprising a mutation. The disclosure further relates to methods of treating a disorder or condition using the IgG4 antibody comprising two heavy chains, wherein each of the heavy chains comprises a human IgG4 constant region comprising a mutation.
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
8.
NEUTRALIZING ANTI-INFLUENZA B ANTIBODIES AND USES THEREOF
The invention relates to antibodies and antigen binding fragments thereof that are capable of binding to influenza B virus hemagglutinin (HA) and neutralizing influenza B virus in two phylogenetically distinct lineages. In one embodiment, the antibody or antigen binding fragment is capable of binding to influenza B virus hemagglutinin and neutralizing influenza B virus in Yamagata and Victoria lineages.
The present disclosure, relates, in general, to methods of treating chronic obstructive pulmonary disease (COPD) using an antibody specific for thymic stromal lymphopoietin (TSLP).
C07K 16/24 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against cytokines, lymphokines or interferons
A61P 11/00 - Drugs for disorders of the respiratory system
The present invention provides a bioconjugation method and compounds for use therein. The bioconjugation method comprises the step of conjugating a biological molecule containing a first unsaturated functional group with a payload comprising a second unsaturated functional group, wherein the first and second unsaturated functional groups are complementary to each other such that conjugation is a reaction of said functional groups via a Diels-Alder reaction which forms a cyclohexene ring.
A61K 47/68 - 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 antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment
A61K 47/69 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additivesTargeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit
C07C 271/22 - Esters of carbamic acids having oxygen atoms of carbamate groups bound to acyclic carbon atoms with the nitrogen atoms of the carbamate groups bound to hydrogen atoms or to acyclic carbon atoms to carbon atoms of hydrocarbon radicals substituted by carboxyl groups
C07D 207/46 - Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with hetero atoms directly attached to the ring nitrogen atom
The disclosure generally provides proteins that bind two epitopes (e.g., a first and a second epitope) and that are bivalent for binding to each of the first and second epitopes. The disclosure also provides for specific binding proteins, including antibodies, which bind to a target protein. The disclosure also provides compositions comprising such proteins, nucleic acid molecules encoding such proteins and methods of making such proteins. The disclosure provides methods of inducing an immune response in a subject as well as methods for treating or preventing cancer in a subject by administering the proteins, nucleic acid molecules and/or compositions to the subject.
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
12.
STEAP2 DIRECTED T-CELL ENGAGERS AND COMPOSITIONS THEREOF
Provided are T ell engaging molecules that bind an antigen on a non-immune cell and an antigen on an immune cell. The T cell engaging molecules can bind STEAP2 on a cancer cell and, e.g., a CD3 on a T cell. The T cell engaging molecules can also bind STEAP2 on a cancer cell and, e.g., a CD8 on a T cell. Alternatively, the T cell engaging molecules can bind STEAP2 on a cancer cell and both CD3 and CD8 on a T cell.
C07K 16/30 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants from tumour cells
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
A61K 47/68 - 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 antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment
The present disclosure, relates, in general, to methods of treating asthma, including severe asthma and eosinophilic asthma, using an antibody specific for thymic stromal lymphopoietin (TSLP).
C07K 16/24 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against cytokines, lymphokines or interferons
Provided herein are clonal Chinese Hamster Ovary (CHO) cells and their use in increasing cellular productivity in biomanufacturing processes. Specifically, the disclosure provides a method of improving specific cellular productivity of a polypeptide of interest in a recombinant cell comprising expressing a nucleic acid encoding the polypeptide of interest in a recombinant cell having a high mitochondrial membrane potential (MMP).
The present disclosure relates to antibodies or fragments thereof comprising an antigen binding domain capable of binding to a CD3 protein or a fragment thereof. The present disclosure also relates to such antibodies that bind to CD3 having optimized affinity to induce T cell activation, but without being associated with excessive cytokine release and reduced tolerability. The disclosure also relates to methods of producing these antibodies and their therapeutic uses.
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
Provided herein are multispecific antibodies containing a lambda charge pair introduced into the interface of a heavy chain and a light chain to reduce chain mispairing.
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
Provided herein are trispecific antibodies containing three antigen binding arms each capable of binding to a different target, wherein each antigen binding arm contains a different lambda or kappa charge pair introduced into the interface of the respective heavy and light chains to reduce chain mispairing.
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
Provided herein is a multispecific antibody containing two antigen binding arms capable of binding to a first target and at least one antigen binding arm capable of binding to a second target. The multispecific antibody includes a lambda charge pair introduced into the interface of a heavy chain and a light chain to reduce chain mispairing.
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
20.
PD-1/TIM-3 BINDING PROTEINS FOR TREATMENT OF NSCLC and cHL
The disclosure relates to methods of treating non-small cell lung cancer (NSCLC) or classical Hodgkin's Lymphoma (cHL) by administering a bispecific antibody, that binds to Programmed Death-1 (PD-1) and T-cell immunoglobulin and mucin domain containing protein-3 (TIM-3), to a subject with NSCLC or cHL in an amount from about 70 mg to about 1500 mg.
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
A61K 9/00 - Medicinal preparations characterised by special physical form
A61K 39/00 - Medicinal preparations containing antigens or antibodies
The disclosure relates to methods of treating cancer by administering binding proteins, including antibodies, that bind to Programmed Death-1 (“PD-1”) and T cell immunoreceptor with Ig and ITIM domains (“TIGIT”) to a subject in an amount from about 70 mg to about 1500 mg.
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
The disclosure relates to methods of treating non-small cell lung cancer (NSCLC) or classical Hodgkin's Lymphoma (cHL) by administering a bispecific antibody, that binds to Programmed Death- 1 (PD-1) and T-cell immunoglobulin and mucin domain containing protein- 3 (TIM-3), to a subject with NSCLC or cHL in an amount from about 70 mg to about 1500 mg.
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
The present disclosure provides binding proteins (e.g., antibodies or antigen binding fragments thereof) that specifically bind to Klebsiella pneumoniae O1 and induce opsonophagocytic killing of Klebsiella (e.g., Klebsiella pneumoniae). The present disclosure also provides methods of reducing Klebsiella (e.g., Klebsiella pneumoniae) or treating or preventing Klebsiella (e.g., Klebsiella pneumoniae) infection in a subject comprising administering the Klebsiella pneumoniae O1 binding proteins, (e.g., antibodies or antigen-binding fragments thereof) to the subject.
C07K 16/12 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from bacteria
A61K 31/407 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil condensed with heterocyclic ring systems, e.g. ketorolac, physostigmine
The present disclosure relates, in general, to methods of treating corticosteroid- dependent asthma, such as oral corticosteroid (OCS)-dependent asthma using an antibody specific for thymic stromal lymphopoietin (TSLP).
C07K 16/24 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against cytokines, lymphokines or interferons
The present disclosure is directed to a monoclonal antibody, or antigen-binding fragment thereof, that specifically binds to a Staphylococcus aureus clumping factor A protein (ClfA), as well as compositions comprising the monoclonal antibody. The disclosure also is directed to methods of treating a Staphylococcus aureus infection by administering the anti-ClfA monoclonal antibody alone, or in combination with a monoclonal antibody that specifically binds to S. aureus alpha toxin (AT) protein to a subject. Bispecific monoclonal antibodies that specifically bind to both ClfA and AT and methods of using the same also are provided.
The disclosure relates to methods of treating cancer by administering binding proteins, including antibodies, that bind to Programmed Death-1 ("PD-1") and T cell immunoreceptor with Ig and ITIM domains ("TIGIT") to a subject in an amount from about 70 mg to about 1500 mg.
The present disclosure relates to antibodies or fragments thereof comprising an antigen binding domain capable of binding to a CDS protein or a fragment thereof. The present disclosure also relates to such antibodies that bind to CDS having optimized affinity to induce T cell activation, but without being associated with excessive cytokine release and reduced tolerability. The disclosure also relates to methods of producing these antibodies and their therapeutic uses.
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
A61K 39/395 - AntibodiesImmunoglobulinsImmune serum, e.g. antilymphocytic serum
C07K 16/30 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants from tumour cells
28.
STEAP2 DIRECTED T-CELL ENGAGERS AND COMPOSITIONS THEREOF
Provided are T cell engaging molecules that bind an antigen on a non-immune cell and an antigen on an immune cell. The T cell engaging molecules can bind STEAP2 on a cancer cell and, e.g., a CD3 on a T cell. The T cell engaging molecules can also bind STEAP2 on a cancer cell and, e.g., a CD8 on a T cell. Alternatively, the T cell engaging molecules can bind STEAP2 on a cancer cell and both CD3 and CD8 on a T cell.
C07K 16/30 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants from tumour cells
A61K 39/395 - AntibodiesImmunoglobulinsImmune serum, e.g. antilymphocytic serum
A61K 47/68 - 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 antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment
A61K 47/68 - 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 antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment
The present invention relates to a pharmaceutical composition comprising an anti-IL-13 antibody or an IL-13-binding fragment thereof, wherein the pharmaceutical composition comprises histidine buffer, a positively charged-excipient (e.g. lysine or arginine) and a surfactant. Such pharmaceutical compositions may be used for treating an IL-13 related disorder, such as atopic dermatitis, asthma, allergic rhinitis, fibrosis, chronic obstructive pulmonary disease, scleroderma, inflammatory bowel disease or Hodgkin's lymphoma.
C07K 16/24 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against cytokines, lymphokines or interferons
A61K 47/18 - AminesAmidesUreasQuaternary ammonium compoundsAmino acidsOligopeptides having up to five amino acids
A61K 47/22 - Heterocyclic compounds, e.g. ascorbic acid, tocopherol or pyrrolidones
A61K 47/26 - Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharidesDerivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
31.
FLUIDIC MIXER UNIT DEVICE FOR NANOPARTICLE PRODUCTION
A device 100 for producing nanoparticles includes a microplate 102 which includes a plurality of fluidic mixing units 104 arranged in an array. Each fluidic mixing unit is configured to produce nanoparticles. The device enables high throughput lipid nanoparticle testing and development, and is configured to generate large numbers of novel or unique nanoparticle formulations.
B01F 25/10 - Mixing by creating a vortex flow, e.g. by tangential introduction of flow components
B01F 25/433 - Mixing tubes wherein the shape of the tube influences the mixing, e.g. mixing tubes with varying cross-section or provided with inwardly extending profiles
Provided herein are multispecific antibodies containing a lambda charge pair introduced into the interface of a heavy chain and a light chain to reduce chain mispairing.
Provided herein is a multispecific antibody containing two antigen binding arms capable of binding to a first target and at least one antigen binding arm capable of binding to a second target. The multispecific antibody includes a lambda charge pair introduced into the interface of a heavy chain and a light chain to reduce chain mispairing.
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
A61K 47/68 - 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 antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment
A61P 1/18 - Drugs for disorders of the alimentary tract or the digestive system for pancreatic disorders, e.g. pancreatic enzymes
C07D 519/00 - Heterocyclic compounds containing more than one system of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring system not provided for in groups or
C07K 16/22 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against growth factors
Provided herein are trispecific antibodies containing three antigen binding arms each capable of binding to a different target, wherein each antigen binding arm contains a different lambda or kappa charge pair introduced into the interface of the respective heavy and light chains to reduce chain mispairing.
Provided herein is an environmentally compatible detergent for use in purification of a recombinantly produced bio-therapeutic. The environmentally compatible detergent includes Laureth-9 and can be used for viral clearance, cell lysis, and removal of impurities such as host cell proteins an endotoxins. Advantageously, Laureth-9 does not adversely impact product quality.
The disclosure is directed to an antibody-drug conjugate (ADC) comprising a monoclonal antibody, or an antigen-binding fragment thereof, directed against B-cell maturation antigen (BCMA) conjugated to a cytotoxin. The disclosure also provides compositions comprising the antibody-drug conjugate and methods of killing multiple myeloma cells (including multiple myeloma stems cells) that express BCMA by contacting multiple myeloma cells with the ADC.
C07K 16/30 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants from tumour cells
A61K 31/202 - Carboxylic acids, e.g. valproic acid having a carboxyl group bound to an acyclic chain of seven or more carbon atoms, e.g. stearic, palmitic or arachidic acid having three or more double bonds, e.g. linolenic acid
A61K 31/4741 - QuinolinesIsoquinolines ortho- or peri-condensed with heterocyclic ring systems condensed with ring systems having oxygen as a ring hetero atom, e.g. tubocuraran derivatives, noscapine, bicuculline
A61K 31/551 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole having two nitrogens as ring hetero atoms, e.g. clozapine, dilazep
A61K 31/7048 - Compounds having saccharide radicals and heterocyclic rings having oxygen as a ring hetero atom, e.g. leucoglucosan, hesperidin, erythromycin, nystatin
A61K 39/00 - Medicinal preparations containing antigens or antibodies
A61K 47/68 - 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 antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment
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
C12N 15/62 - DNA sequences coding for fusion proteins
37.
BISPECIFIC PD-1 AND TIGIT BINDING PROTEINS AND USES THEREOF
The disclosure relates to binding proteins, including antibodies, that bind to Programmed Death-1 (“PD-1”) and T cell immunoreceptor with Ig and ITIM domains (“TIGIT”). The disclosure also provides compositions comprising such binding proteins and nucleic acid molecules encoding such binding proteins. The disclosure further relates to methods of treating a disorder or condition using such binding proteins.
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
A61K 39/00 - Medicinal preparations containing antigens or antibodies
A61K 39/395 - AntibodiesImmunoglobulinsImmune serum, e.g. antilymphocytic serum
A61K 45/06 - Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
The present invention relates to improved pharmaceutical compositions that contain high concentrations of one or more protein biomolecule(s). In particular, the invention relates to such pharmaceutical compositions that include one or more amino acid molecules, particularly arginine, alanine, glycine, lysine or proline, or derivatives and salts thereof, or mixtures thereof, as stabilizing compounds. The inclusion of such stabilizing compounds decreases reconstitution time whilst improving and/or maintaining the long-term stability of the protein biomolecule, so as to facilitate the treatment, management, amelioration and/or prevention of a disease or condition by the pharmaceutical composition. The invention particularly pertains to such pharmaceutical compositions that lack, or substantially lack, a sugar stabilizing agent.
The present disclosure, relates, in general, to methods of treating chronic rhinosinusitis, with or without nasal polyps, using an antibody specific for thymic stromal lymphopoietin (TSLP).
C07K 16/24 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against cytokines, lymphokines or interferons
40.
MODIFIED FCRN BINDING FRAGMENTS WITH IMPROVED HALF-LIFE
The present disclosure relates to modified FcRn binding fragments with improved half-life, specifically fusion proteins and polypeptides comprising said modified FcRn binding fragments, and methods of manufacturing said fusion proteins and their use in methods of treatment.
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
A61K 47/68 - 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 antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment
41.
COMPOSITIONS AND METHODS OF TREATING CANCER WITH CHIMERIC ANTIGEN RECEPTORS TARGETING CLAUDIN 18.2
This disclosure relates to compositions and methods for treating cancer using chimeric antigen receptor T cells and/or antigen binding domains targeting CLDN18.2.
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
A61K 39/00 - Medicinal preparations containing antigens or antibodies
The invention relates to antibodies and binding fragments thereof that are capable of binding to influenza A virus hemagglutinin and neutralizing at least one group 1 subtype and at least 1 group 2 subtype of influenza A virus.
A61K 31/215 - Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids
A61K 31/7012 - Compounds having a free or esterified carboxyl group attached, directly or through a carbon chain, to a carbon atom of the saccharide radical, e.g. glucuronic acid, neuraminic acid
A61K 39/395 - AntibodiesImmunoglobulinsImmune serum, e.g. antilymphocytic serum
A61K 39/42 - AntibodiesImmunoglobulinsImmune serum, e.g. antilymphocytic serum viral
A61K 45/06 - Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
C07K 16/10 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from viruses from RNA viruses
Provided herein is a novel rAAV-based HSV production method that includes two engineered cell lines: engineered CHO cells to produce multiple AAV serotypes and engineered BHK-21 to produce rHSV-1 stocks that are used in the production of rAAVs in CHO cells. The developed method provides a scalable, serum-free manufacturing platform.
C07K 14/71 - ReceptorsCell surface antigensCell surface determinants for growth factorsReceptorsCell surface antigensCell surface determinants for growth regulators
A61K 35/17 - LymphocytesB-cellsT-cellsNatural killer cellsInterferon-activated or cytokine-activated lymphocytes
A61K 38/17 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from animalsPeptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from humans
A61K 39/00 - Medicinal preparations containing antigens or antibodies
A61K 39/395 - AntibodiesImmunoglobulinsImmune serum, e.g. antilymphocytic serum
A61K 45/06 - Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
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 16/30 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants from tumour cells
C07K 16/32 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against translation products from oncogenes
The present invention provides a method for producing encapsulated natively-paired scFv amplicons, by encapsulating single cells in droplets, wherein the droplets further contain reagents for amplifying and sinking native pairings of heavy and light chain variable domain amplicons from single encapsulated cells; lysing the single encapsulated cells; and generating the encapsulated natively-paired scFv amplicons, wherein each scFv amplicon comprises a native pairing of heavy and light chain variable domain amplicons.
A tri-functional linker moiety: formula (I), where X and Y are linking chains, and its use for preparing dual-mechanistic drug conjugates, preferably in a site-specific manner.
A tri-functional linker moiety: formula (I), where X and Y are linking chains, and its use for preparing dual-mechanistic drug conjugates, preferably in a site-specific manner.
A61K 47/68 - 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 antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment
A61K 47/54 - 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 compound
C07D 207/452 - 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 three double bonds between ring members or between ring members and non-ring members having two doubly-bound oxygen atoms directly attached in positions 2 and 5 with only hydrogen atoms or radicals containing only hydrogen and carbon atoms directly attached to other ring carbon atoms, e.g. maleimide with hydrocarbon radicals, substituted by hetero atoms, directly attached to the ring nitrogen atom
47.
COMPOSITIONS AND METHODS OF TREATING CANCER WITH CHIMERIC ANTIGEN RECEPTORS TARGETING CLAUDIN 18.2
This disclosure relates to compositions and methods for treating cancer using chimeric antigen receptor T cells and/or antigen binding domains targeting CLDN18.2.
The present invention provides molecules, including proteins, more particularly, immunoglobulins whose in vivo half-lives are altered (increased or decreased) by the presence of an IgG constant domain, or FcRn binding fragment thereof (e.g., an Fc region or hinge-Fe region) (e.g., from a human IgG, e.g., human IgG1), that have modifications of one or more of amino acid residues in at least the CH3 domain.
C07K 16/40 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against enzymes
A61K 47/68 - 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 antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment
C07K 16/00 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies
C07K 16/10 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from viruses from RNA viruses
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
Provided herein are methods for manufacturing, expanding, and/or generating genetically modified T cells comprising a chimeric antigen receptor (CAR) or T-cell receptor (TCR).
C12N 5/0783 - T cellsNK cellsProgenitors of T or NK cells
C07K 16/30 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants from tumour cells
C07K 16/40 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against enzymes
The disclosure generally provides proteins that bind two epitopes (e.g., a first and a second epitope) and that are bivalent for binding to each of the first and second epitopes. The disclosure also provides for specific binding proteins, including antibodies, which bind to a target protein. The disclosure also provides compositions comprising such proteins, nucleic acid molecules encoding such proteins and methods of making such proteins. The disclosure provides methods of inducing an immune response in a subject as well as methods for treating or preventing cancer in a subject by administering the proteins, nucleic acid molecules and/or compositions to the subject.
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
Provided herein are methods of treating cancer in a human subject, comprising administering to the subject: i) an antibody-drug conjugate (ADC) comprising an antibody, a cleavable linker and a cytotoxic agent, and ii) a bispecific checkpoint inhibitor. Further provided herein are kits comprising i) an antibody-drug conjugate (ADC) comprising an antibody, a cleavable linker and a cytotoxic agent, and ii) a bispecific checkpoint inhibitor.
A61K 47/68 - 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 antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment
A61K 39/395 - AntibodiesImmunoglobulinsImmune serum, e.g. antilymphocytic serum
The invention relates to antibodies and antigen binding fragments thereof that are capable of binding to influenza B virus hemagglutinin (HA) and neutralizing influenza B virus in two phylogenetically distinct lineages. In one embodiment, the antibody or antigen binding fragment is capable of binding to influenza B virus hemagglutinin and neutralizing influenza B virus in Yamagata and Victoria lineages.
Provided herein are methods of treating cancer in a human subject, comprising administering to the subject: i) an antibody-drug conjugate (ADC) comprising an antibody, a cleavable linker and a cytotoxic agent, and ii) a bispecific checkpoint inhibitor. Further provided herein are kits comprising i) an antibody-drug conjugate (ADC) comprising an antibody, a cleavable linker and a cytotoxic agent, and ii) a bispecific checkpoint inhibitor.
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
A61K 31/436 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a six-membered ring having oxygen as a ring hetero atom, e.g. rapamycin
A61K 31/437 - 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 38/17 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from animalsPeptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from humans
A61K 39/395 - AntibodiesImmunoglobulinsImmune serum, e.g. antilymphocytic serum
A61K 47/68 - 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 antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment
C07K 16/30 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants from tumour cells
Provided herein are methods for manufacturing, expanding, and/or generating genetically modified T cells comprising a chimeric antigen receptor (CAR) or T-cell receptor (TCR).
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
55.
TREATMENT METHODS USING ANTI-CD73 AND ANTI-PD-L1 ANTIBODIES AND CHEMOTHERAPY
This disclosure relates to methods of treating cancers in a human patient (e.g., metastatic pancreatic ductal adenocarcinoma (PD AC)), comprising administering an anti-CD73 antibody or antigen binding fragment thereof and chemotherapy. The disclosure also relates to methods for the treatment of tumors comprising administering an anti-CD73 antibody or antigen-binding fragment thereof in combination with a PD-L1 antibody or an antigen-binding fragment thereof and chemotherapy.
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
A61K 31/7068 - Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom containing condensed or non-condensed pyrimidines having oxo groups directly attached to the pyrimidine ring, e.g. cytidine, cytidylic acid
A61K 31/337 - Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having four-membered rings, e.g. taxol
A61K 31/555 - Heterocyclic compounds containing heavy metals, e.g. hemin, hematin, melarsoprol
A61K 31/519 - PyrimidinesHydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
A61K 31/513 - PyrimidinesHydrogenated pyrimidines, e.g. trimethoprim having oxo groups directly attached to the heterocyclic ring, e.g. cytosine
G16H 20/40 - ICT specially adapted for therapies or health-improving plans, e.g. for handling prescriptions, for steering therapy or for monitoring patient compliance relating to mechanical, radiation or invasive therapies, e.g. surgery, laser therapy, dialysis or acupuncture
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
G16H 50/50 - ICT specially adapted for medical diagnosis, medical simulation or medical data miningICT specially adapted for detecting, monitoring or modelling epidemics or pandemics for simulation or modelling of medical disorders
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
G01N 33/574 - ImmunoassayBiospecific binding assayMaterials therefor for cancer
57.
OPTIMIZED RATIOS OF AMINO ACIDS AND SUGARS AS AMORPHOUS STABILIZING COMPOUNDS IN PHARMACEUTICAL COMPOSITIONS CONTAINING HIGH CONCENTRATIONS OF PROTEIN-BASED THERAPEUTIC AGENTS
The present invention relates to improved pharmaceutical compositions that contain high concentrations of one or more protein biomolecule(s). In particular, the invention relates to pharmaceutical compositions that include an optimized ratio of protein biomolecule to an amorphous stabilizing compound or compounds, especially a sugar, such as sucrose, trehalose, glucose, lactose or sorbitol, or mixtures thereof, or one or more amino acid molecules such as arginine, alanine, glycine, lysine or proline, or derivatives and salts thereof, or mixtures thereof. The inclusion of such amorphous stabilizing compound(s), at such optimized ratio, provides acceptable long-term stability of the protein biomolecule, and facilitates shorter lyophilization time, more specifically shorter drying time, even more specifically shorter primary drying time.
INSTITUT NATIONAL DE LA SANTÉ ET DE LA RECHERCHE MÉDICALE (France)
MEDIMMUNE, LLC (USA)
UNIVERSITÉ PARIS CITÉ (France)
Inventor
Dagher, Rania
Kolbeck, Roland
Humbles, Alison H.
Aubier, Michel
Abstract
Chronic obstructive pulmonary disease (COPD) is a heterogeneous disease with pulmonary and extra-pulmonary manifestations. COPD heterogeneity is poorly understood and insights into molecular mechanisms is required to provide better treatment with targeted therapies. The inventors collected serum samples from (241) COPD subjects in the COBRA cohort and measured the expression of (1305) proteins using SOMAscan proteomic platform. Modular analyses and clustering of the proteomics were applied to identify disease subtypes. Cluster discoveries were revalidated during a follow up visit, and confirmed in a different COPD cohort. Unsupervised clustering using protein modules identified two clusters within COPD subjects. One cluster presented a higher expression of proteins associated with enhanced immune and pro-survival activities, host defense and cell renewal. Subjects in this cluster had a lower incidence of exacerbations, unscheduled medical visits, emphysema and diabetes. These protein signatures were conserved during a follow up visit, and validated in another COPD cohort. Among the 96 proteins, the inventors identified a small specific signature consisting of 15 proteins that were able to accurately differentiate the two patient clusters. This signature would thus be useful for predicting the clinical outcome of patients suffering from COPD.
The present invention relates to a method of purifying albumin-fusion proteins to reduce the level of oxidation of susceptible amino acid residues. The method comprises an affinity matrix chromatography step and an anion exchange chromatography step. The purified albumin-fusion proteins have low levels of oxidation and retain their enhanced half-life in vivo and its bioactivity. In some embodiments, the albumin-fusion protein comprises a scaffold, such as human Tenascin C scaffold. Compositions comprising the albumin-fusion protein are further disclosed.
A61K 47/64 - Drug-peptide, drug-protein or drug-polyamino acid conjugates, i.e. the modifying agent being a peptide, protein or polyamino acid which is covalently bonded or complexed to a therapeutically active agent
The present disclosure provides methods of administering bispecific antibodies and antigen-binding fragments thereof that specifically bind to human Programmed cell-death-1 (PD-1) and Cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) to a subject in need thereof, for example, a subject with cancer.
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
A61K 31/4439 - Non-condensed pyridinesHydrogenated derivatives thereof containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole
The present invention provides a bioconjugation method and compounds for use therein. The bioconjugation method comprises the step of conjugating a biological molecule containing a first unsaturated functional group with a payload comprising a second unsaturated functional group, wherein the first and second unsaturated functional groups are complementary to each other such that conjugation is a reaction of said functional groups via a Diels-Alder reaction which forms a cyclohexene ring.
A61K 47/68 - 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 antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment
A61K 47/69 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additivesTargeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit
C07C 271/22 - Esters of carbamic acids having oxygen atoms of carbamate groups bound to acyclic carbon atoms with the nitrogen atoms of the carbamate groups bound to hydrogen atoms or to acyclic carbon atoms to carbon atoms of hydrocarbon radicals substituted by carboxyl groups
C07D 207/46 - Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with hetero atoms directly attached to the ring nitrogen atom
62.
TREATMENT METHODS USING CTLA-4 AND PD-1 BISPECIFIC ANTIBODIES
The present disclosure provides methods of administering bispecific antibodies and antigen-binding fragments thereof that specifically bind to human Programmed cell-death-1 (PD- 1) and Cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) to a subject in need thereof, for example, a subject with cancer.
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
The disclosure provides chimeric antigen receptors and antibodies that comprise antigen-binding domains that specifically bind human STEAP2, nucleotides that encode the same, cells comprising the same, and methods of using the same in the treatment of cancer (e.g., prostate cancer).
The disclosure provides methods for the isolation, separation, and purification of antibodies. The method comprises an affinity chromatography capture step, anion exchange chromatography polishing step, and cation exchange chromatography polishing step.
B01D 15/38 - Selective adsorption, e.g. chromatography characterised by the separation mechanism involving specific interaction not covered by one or more of groups , e.g. affinity, ligand exchange or chiral chromatography
C07K 1/22 - Affinity chromatography or related techniques based upon selective absorption processes
B01D 15/36 - Selective adsorption, e.g. chromatography characterised by the separation mechanism involving ionic interaction, e.g. ion-exchange, ion-pair, ion-suppression or ion-exclusion
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 1/16 - ExtractionSeparationPurification by chromatography
C07K 1/36 - ExtractionSeparationPurification by a combination of two or more processes of different types
Provided herein are methods for treating, reducing or preventing influenza A virus infection in a patient, as well as compositions and articles of manufacture for treating, reducing or preventing influenza A virus infection in a patient.
A61K 31/215 - Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids
A61K 31/7012 - Compounds having a free or esterified carboxyl group attached, directly or through a carbon chain, to a carbon atom of the saccharide radical, e.g. glucuronic acid, neuraminic acid
A61P 31/16 - Antivirals for RNA viruses for influenza or rhinoviruses
C07K 16/10 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from viruses from RNA viruses
A61K 39/00 - Medicinal preparations containing antigens or antibodies
Provided herein are clonal Chinese Hamster Ovary (CHO) cells and their use in increasing cellular productivity in biomanufacturing processes. Specifically, the disclosure provides a method of improving specific cellular productivity of a polypeptide of interest in a recombinant cell comprising expressing a nucleic acid encoding the polypeptide of interest in a recombinant cell having a high mitochondrial membrane potential (MMP).
C12P 21/06 - Preparation of peptides or proteins produced by the hydrolysis of a peptide bond, e.g. hydrolysate products
C12N 15/00 - Mutation or genetic engineeringDNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purificationUse of hosts therefor
G01N 33/567 - ImmunoassayBiospecific binding assayMaterials therefor using specific carrier or receptor proteins as ligand binding reagent utilising isolate of tissue or organ as binding agent
C07H 21/04 - Compounds containing two or more mononucleotide units having separate phosphate or polyphosphate groups linked by saccharide radicals of nucleoside groups, e.g. nucleic acids with deoxyribosyl as saccharide radical
67.
COMPOSITIONS AND METHODS FOR DELIVERING PHARMACEUTICALLY ACTIVE AGENTS
The invention relates to modified lysines of the formula (I). The invention further relates to polypeptides comprising one or more modified lysine residues, pharmaceutical delivery systems comprising these polypeptides, pharmaceutical compositions containing them, and to their use in therapy.
The invention relates to modified lysines of the formula (I). The invention further relates to polypeptides comprising one or more modified lysine residues, pharmaceutical delivery systems comprising these polypeptides, pharmaceutical compositions containing them, and to their use in therapy.
C07D 279/12 - 1,4-ThiazinesHydrogenated 1,4-thiazines not condensed with other rings
C07D 295/15 - Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals with the ring nitrogen atoms and the carbon atoms with three bonds to hetero atoms attached to the same carbon chain, which is not interrupted by carbocyclic rings to an acyclic saturated chain
A61K 47/69 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additivesTargeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit
A61K 47/64 - Drug-peptide, drug-protein or drug-polyamino acid conjugates, i.e. the modifying agent being a peptide, protein or polyamino acid which is covalently bonded or complexed to a therapeutically active agent
68.
BLOOD-BASED TUMOR MUTATION BURDEN PREDICTS OVERALL SURVIVAL IN NSCLC
The disclosure generally relates to methods for treating non-small cell lung cancer patients based on use of blood-based tumor mutation burden to predict overall survival in patients treated with durvalumab, tremelimumab, and/or a chemotherapy agent. The disclosure also relates to methods for treating non-small cell lung cancer patients based on identification of mutations in circulating tumor DNA associated with sensitivity or resistance to immunotherapy.
C12Q 1/6886 - Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material for cancer
A61K 39/395 - AntibodiesImmunoglobulinsImmune serum, e.g. antilymphocytic serum
Provided are formulations of an antibody that specifically binds of endothelial lipase. The provided formulations may be in liquid form or reconstituted from a lyophilized form. The formulations have viscosities suitable for injection and prevent reversible self-association of the antibody, precipitation and cloudiness.
A61K 39/395 - AntibodiesImmunoglobulinsImmune serum, e.g. antilymphocytic serum
C07K 16/40 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against enzymes
A61K 47/18 - AminesAmidesUreasQuaternary ammonium compoundsAmino acidsOligopeptides having up to five amino acids
A61K 47/22 - Heterocyclic compounds, e.g. ascorbic acid, tocopherol or pyrrolidones
A61K 47/26 - Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharidesDerivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
A61K 9/00 - Medicinal preparations characterised by special physical form
A61K 9/19 - Particulate form, e.g. powders lyophilised
A61P 9/00 - Drugs for disorders of the cardiovascular system
A61P 9/10 - Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
70.
ANTI-STEAP2 CHIMERIC ANTIGEN RECEPTORS AND USES THEREOF
The disclosure provides chimeric antigen receptors and antibodies that comprise antigen-binding domains that specifically bind human STEAP2, nucleotides that encode the same, cells comprising the same, and methods of using the same in the treatment of cancer (e.g., prostate cancer).
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
A61K 48/00 - Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseasesGene therapy
Binding molecules, including bispecific antibodies that include at least two anti-influenza binding domains are disclosed, including binding molecules having a first binding domain that specifically binds influenza A virus and a second binding domain that specifically binds influenza B virus.
Provided herein are methods of treating non-small cell lung cancers comprising administering an effective amount of MEDI4736 or an antigen-binding fragment thereof and tremelimumab or an antigen-binding fragment thereof.
A61K 39/395 - AntibodiesImmunoglobulinsImmune serum, e.g. antilymphocytic serum
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 16/12 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from bacteria
A61K 31/407 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil condensed with heterocyclic ring systems, e.g. ketorolac, physostigmine
A61K 39/00 - Medicinal preparations containing antigens or antibodies
A61K 39/40 - AntibodiesImmunoglobulinsImmune serum, e.g. antilymphocytic serum bacterial
This application provides improved cell culture media and cell culture methods comprising N-acetylcysteine. These improved cell culture media and cell culture methods increase cell viability, cellular growth rate and/or reduce cell doubling time of cholesterol auxotrophic cells, myeloma cells, and hybridoma cells.
C12N 5/00 - Undifferentiated human, animal or plant cells, e.g. cell linesTissuesCultivation or maintenance thereofCulture media therefor
C12P 21/02 - Preparation of peptides or proteins having a known sequence of two or more amino acids, e.g. glutathione
C07K 16/00 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies
C07K 16/24 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against cytokines, lymphokines or interferons
75.
Compositions and Methods of Treating Cancer with Chimeric Antigen Receptors Targeting Glypican 3
C07K 16/30 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants from tumour cells
The present invention relates to a pharmaceutical composition comprising an anti-IL-13 antibody or an IL-13-binding fragment thereof, wherein the pharmaceutical composition comprises histidine buffer, a positively charged-excipient (e.g. lysine or arginine) and a surfactant. Such pharmaceutical compositions may be used for treating an IL-13 related disorder, such as atopic dermatitis, asthma, allergic rhinitis, fibrosis, chronic obstructive pulmonary disease, scleroderma, inflammatory bowel disease or Hodgkin's lymphoma.
C07K 16/24 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against cytokines, lymphokines or interferons
A61K 9/00 - Medicinal preparations characterised by special physical form
A61K 39/395 - AntibodiesImmunoglobulinsImmune serum, e.g. antilymphocytic serum
A61K 47/18 - AminesAmidesUreasQuaternary ammonium compoundsAmino acidsOligopeptides having up to five amino acids
The present disclosure provides methods of administering antibodies and antigen-binding fragments thereof that specifically bind to human endothelial lipase (EL) to a subject in need thereof, for example, a subject with cardiovascular disease.
C07K 16/40 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against enzymes
A61K 9/00 - Medicinal preparations characterised by special physical form
A61P 9/10 - Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
78.
COMBINATION THERAPY USING GLUCAGON AND GLP-1 CO-AGONISTS FOR THE TREATMENT OF OBESITY
Provided herein are methods of improving glycemic control, reducing weight, and/or treating type 2 diabetes mellitus in human patients comprising administering GLP-1/glucagon agonist peptides, dapagliflozin, and metformin.
A61K 31/7034 - Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages attached to a carbocyclic compound, e.g. phloridzin
The disclosure relates to binding proteins, including antibodies, that bind to Programmed Death-1 (“PD-1”) and T cell immunoreceptor with Ig and ITIM domains (“TIGIT”). The disclosure also provides compositions comprising such binding proteins and nucleic acid molecules encoding such binding proteins. The disclosure further relates to methods of treating a disorder or condition using such binding proteins.
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
A61K 39/395 - AntibodiesImmunoglobulinsImmune serum, e.g. antilymphocytic serum
A61K 45/06 - Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
The present invention relates to the use of components of the IL23 pathway as biomarkers, e.g., IL22, LCN2 and combinations thereof, to stratify or identify populations of patients suffering from IL23-mediated diseases (e.g., Crohn's disease) responsive to treatment with an anti-IL23 antagonist (including, e.g., anti-IL23 antibodies or antigen-binding fragments thereof). Levels of IL23 pathway biomarkers above or below a predetermined threshold can be used, for example, (i) to determine whether a patient with an IL23-mediated disease or disorder such a Crohn's disease is eligible or non-eligible for treatment with a therapeutic agent (e.g., an anti-IL23 antibody), (ii) to determine whether treatment with a certain agent should be commenced, suspended, or modified, (iii) to diagnose whether the IL23-mediated disease is treatable or not treatable with a specific therapeutic agent, or (iv) to predict the outcome of treating the IL23-mediated disease with a specific therapeutic agent.
C07K 16/24 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against cytokines, lymphokines or interferons
A61P 1/04 - Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
The present invention provides conjugates of a first polypeptide and a second polypeptide wherein the link between the first polypeptide and the second polypeptide comprises the following moiety.
C07C 13/08 - Monocyclic hydrocarbons or acyclic hydrocarbon derivatives thereof with a five-membered ring
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 14/00 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof
82.
MODIFIED FCRN BINDING FRAGMENTS WITH IMPROVED HALF-LIFE
The present disclosure relates to modified FcRn binding fragments with improved half-life, specifically fusion proteins and polypeptides comprising said modified FcRn binding fragments, and methods of manufacturing said fusion proteins and their use in methods of treatment.
A61K 39/395 - AntibodiesImmunoglobulinsImmune serum, e.g. antilymphocytic serum
A61K 47/68 - 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 antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment
C07K 16/00 - Immunoglobulins, e.g. monoclonal or polyclonal 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
83.
BISPECIFIC PD-1 AND TIGIT BINDING PROTEINS AND USES THEROF
The disclosure relates to binding proteins, including antibodies, that bind to Programmed Death-1 ("PD-1") and T cell immunoreceptor with Ig and ITIM domains ("TIGIT"). The disclosure also provides compositions comprising such binding proteins and nucleic acid molecules encoding such binding proteins. The disclosure further relates to methods of treating a disorder or condition using such binding proteins.
A61K 39/395 - AntibodiesImmunoglobulinsImmune serum, e.g. antilymphocytic serum
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
Provided are methods of treating bladder cancer (e.g., urothelial carcinoma, UC) in a subject having bladder cancer, e.g., UC, with an effective dose regimen of an anti-PD-L1 antibody, e.g., durvalumab, or an antigen binding fragment thereof. Also provided are methods in which an anti-PD-L1 antibody is used in combination with another immunotherapeutic agent, e.g., tremelimumab to treat a bladder cancer, e.g., UC, in a subject having bladder cancer. In some cases, the subject undergoing treatment is identified as having a bladder cancer or tumor that is PD-L1-low/neg, or PD-L1-high. Methods are also provided in which anti-PD-L1 antibody treatment of bladder cancer is used following a standard of care or first-line therapy in subjects who have progressed following such therapies or who have relapsed after a prior treatment regimen.
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
A61K 9/00 - Medicinal preparations characterised by special physical form
G01N 33/542 - ImmunoassayBiospecific binding assayMaterials therefor with immune complex formed in liquid phase with steric inhibition or signal modification, e.g. fluorescent quenching
The present disclosure provides methods of altering engagement between T-cell immunoglobulin and mucin domain containing protein-3 (TIM-3) and phosphatidylserine (PS) in a subject. Also provided are methods of treatment using TIM- 3 binding protein wherein the TIM- 3 binding domain specifically binds to the C'C" and DE loops of the immunoglobulin variable (IgV) domain of TIM-3.
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
The present disclosure provides methods of altering engagement between T-cell immunoglobulin and mucin domain containing protein-3 (TIM-3) and phosphatidylserine (PS) in a subject. Also provided are methods of treatment using TIM-3 binding protein wherein the TIM-3 binding domain specifically binds to the C′C″ and DE loops of the immunoglobulin variable (IgV) domain of TIM-3.
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
A solid pharmaceutical dosage form testing apparatus and a method are presented. The solid pharmaceutical dosage form testing apparatus includes a striker component, an impact platform, a sensor data acquisition system, and a solid dosage form placement mechanism. The solid dosage form placement mechanism has first and second push components that are movable toward each other to position a solid dosage form at an impact site. The method includes performing an impact strike test on a first plurality of solid dosage forms, and measuring a plurality of peak impact force values. The method may include performing a drop test on a second plurality of solid dosage forms, and measuring a plurality of physical defect rates. The method may include determining a model that describes a relationship between peak impact force values and physical defect rates, and determining, based on the model, a predicted physical defect rate.
G01N 3/303 - Investigating strength properties of solid materials by application of mechanical stress by applying a single impulsive force generated only by free-falling weight
Provided are methods for treating cancer with an Aurora kinase B inhibitor comprising determining if a cancer cell has a chromosomal amplification at location 22q11 on chromosome 22. Also provided are methods for treating cancer with an Aurora kinase B inhibitor comprising determining if a cancer cell has a gene with an increased copy number at location 22q11 on chromosome 22. Further provided are methods of determining if a cancer cell or a subject having cancer are amenable to treatment with an Aurora kinase B inhibitor.
A61K 31/00 - Medicinal preparations containing organic active ingredients
A61K 31/517 - PyrimidinesHydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with carbocyclic ring systems, e.g. quinazoline, perimidine
A61K 31/506 - PyrimidinesHydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
A61K 45/06 - Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
C12N 15/00 - Mutation or genetic engineeringDNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purificationUse of hosts therefor
C12Q 1/00 - Measuring or testing processes involving enzymes, nucleic acids or microorganismsCompositions thereforProcesses of preparing such compositions
The present disclosure is directed to human GDF-15-binding antibodies and antigen-binding fragments thereof. The antibodies and fragments can be used, for example, to detect human GDF-15 and/or in methods of treating cancer or body weight loss, including cachexia, associated with over-expression of human GDF-15.
The present disclosure is directed to human GDF-15-binding antibodies and antigen-binding fragments thereof. The antibodies and fragments can be used, for example, to detect human GDF-15 and/or in methods of treating cancer or body weight loss, including cachexia, associated with over-expression of human GDF-15.
The disclosure generally provides proteins that bind two epitopes (e.g., a first and a second epitope) and that are bivalent for binding to each of the first and second epitopes. The disclosure also provides for specific binding proteins, including antibodies, which bind to a target protein. The disclosure also provides compositions comprising such proteins, nucleic acid molecules encoding such proteins and methods of making such proteins. The disclosure provides methods of inducing an immune response in a subject as well as methods for treating or preventing cancer in a subject by administering the proteins, nucleic acid molecules and/or compositions to the subject.
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
The disclosure relates to methods and compositions for the treatment of a B-cell malignancy. Specifically, the disclosure relates to a B-cell malignancy medicament or composition, comprising: (a) an antibody-drug conjugate (ADC) comprising an antibody or antigen-binding fragment thereof that binds to B-cell maturation antigen (BCMA), conjugated to a nucleic acid cross-linking agent; and (b) a proteasome inhibitor.
A61K 47/68 - 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 antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment
A61K 31/407 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil condensed with heterocyclic ring systems, e.g. ketorolac, physostigmine
A61K 31/427 - Thiazoles not condensed and containing further heterocyclic rings
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
93.
CCL20 AS A PREDICTOR OF CLINICAL RESPONSE TO IL23-ANTAGONISTS
The present invention relates to the use of the Chemokine (C—C motif) ligand 20 (CCL20) as a biomarker to stratify or identify populations of patients suffering from interleukin-23 (IL23)-mediated diseases (e.g., Crohn's disease) responsive to treatment with an, anti-IL23 antagonist (including, e.g., anti-IL23 antibodies). Levels of CCL20 above or below a predetermined threshold can be used, for example, (i) to determine whether a patient with an IL23-mediated disease or disorder such a Crohn's disease is eligible or non-eligible for treatment with a therapeutic agent, (ii) to determine whether treatment with a certain agent should be commenced, suspended, or modified, (iii) to diagnose whether the IL23-mediated disease is treatable or not treatable with a specific therapeutic agent, or (iv) to predict the outcome of treating the IL23-mediated disease with a specific therapeutic agent. CCL20 can be used in combination with other IL23 pathway biomarkers such as IL22 and/or lipocalin-2 (LCN2).
C07K 16/24 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against cytokines, lymphokines or interferons
G01N 33/68 - Chemical analysis of biological material, e.g. blood, urineTesting involving biospecific ligand binding methodsImmunological testing involving proteins, peptides or amino acids
A61K 39/395 - AntibodiesImmunoglobulinsImmune serum, e.g. antilymphocytic serum
H. LEE MOFFITT CANCER CENTER AND RESEARCH INSTITUTE INC. (USA)
THE USA, AS REPRESENTED BY THE SECRETARY, DEPARTMENT OF HEALTH AND HUMAN SERVICES (USA)
Inventor
Carlesso, Gianluca
Emtage, Peter
Close, David
Siu, Lillian Lai-Yun
Chavez, Julio
Moscow, Jeffrey A.
Abstract
The present disclosure provides anti-ICOS antibodies and antigen-binding fragments thereof for the treatment of T-Cell lymphomas, including, e.g., peripheral T-cell lymphomas, angioimmunoblastic T-cell lymphomas, cutaneous T-cell lymphomas, and follicular lymphomas.
A61K 39/00 - Medicinal preparations containing antigens or antibodies
A61K 47/68 - 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 antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment
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
95.
TREATMENT METHODS USING ANTI-BCMA ANTIBODY-DRUG CONJUGATES
This disclosure relates to methods of treating cancers in a human patient (e.g., Multiple myeloma (MM)) comprising administration of an antibody-drug conjugate (ADC) comprising a monoclonal antibody, or an antigen-binding fragment thereof, directed against B-cell maturation antigen (BCMA) conjugated to a cytotoxin. The disclosure also provides compositions comprising the antibody-drug conjugate and methods of killing multiple myeloma cells (including multiple myeloma stems cells) that express BCMA by contacting multiple myeloma cells with the ADC.
A61K 39/395 - AntibodiesImmunoglobulinsImmune serum, e.g. antilymphocytic serum
A61K 47/68 - 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 antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment
C07K 16/30 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants from tumour cells
C12Q 1/689 - Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for detection or identification of organisms for bacteria
A61K 39/00 - Medicinal preparations containing antigens or antibodies
Disclosed are methods for testing the presence and/or activity of glutathione system components and thioredoxin system components during the manufacturing process of disulfide bond-containing proteins. Also disclosed are methods for mitigating reduction of disulfide bonds during the manufacturing process, and for lowering the reduction potential of disulfide bond-containing proteins. Provided are compositions, kits, and methods for mitigating reduction and diminishing reduction potential of disulfide bond-containing proteins during protein manufacturing processes.
This disclosure relates to methods of treating cancers in a human patient (e.g., metastatic pancreatic ductal adenocarcinoma (PD AC)), comprising administering an anti-CD73 antibody or antigen binding fragment thereof and chemotherapy. The disclosure also relates to methods for the treatment of tumors comprising administering an anti-CD73 antibody or antigen-binding fragment thereof in combination with a PD-L1 antibody or an antigen-binding fragment thereof and chemotherapy.
A61K 39/395 - AntibodiesImmunoglobulinsImmune serum, e.g. antilymphocytic serum
A61K 39/00 - Medicinal preparations containing antigens or antibodies
C07K 16/30 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants from tumour cells
S. aureus alpha toxin (AT) protein to a subject. Bispecific monoclonal antibodies that specifically bind to both ClfA and AT and methods of using the same also are provided.
C07K 16/12 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from bacteria
A61K 31/407 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil condensed with heterocyclic ring systems, e.g. ketorolac, physostigmine
