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Regeneron Pharmaceuticals, Inc.

Regeneron Pharmaceuticals, Inc. Patent applications
Patent application numberTitlePublished
20120135010HIGH AFFINITY HUMAN ANTIBODIES TO HUMAN IL-4 RECEPTOR - An isolated human antibody or antigen binding fragment thereof which binds to human interleukin-4 receptor alpha (hIL-4Rα) with an affinity constant (K05-31-2012
20120128679Human Antibodies to the Glucagon Receptor - The present invention provides antibodies that bind to the human glucagon receptor, designated GCGR and methods of using same. According to certain embodiments of the invention, the antibodies are fully human antibodies that bind to human GCGR. The antibodies of the invention are useful for lowering blood glucose levels and blood ketone levels and are also useful for the treatment of diseases and disorders associated with one or more GCGR biological activities, including the treatment of diabetes, diabetic ketoacidosis and long-term complications associated with diabetes, or other metabolic disorders characterized in part by elevated blood glucose levels.05-24-2012
20120114665HUMAN ANTIBODIES TO HUMAN RANKL - Isolated human antibodies or antigen-binding fragments thereof, which specifically bind to human RANKL and block hRANKL binding to a RANK receptor, are provided. The antibodies are useful in preventing or treating disorders and/or diseases, which are associated with RANKL/RANK interactions, including bone disorders or cancer.05-10-2012
20120114654HUMAN ANTIBODIES TO HUMAN TNF-LIKE LIGAND 1A (TL1A) - A fully human antibody or antigen-binding fragment of a human antibody that specifically binds and inhibits human TNF-like ligand 1A (hTL1A) is provided. The human anti-hTL1A antibodies are useful in treating diseases or disorders associated with TL1A, such as inflammatory diseases or disorders, e.g., inflammatory bowel diseases, including ulcerative colitis and Crohn's disease, rheumatoid arthritis, and the like; autoimmune diseases or disorders, such as multiple sclerosis, diabetes, and the like; and allergic reactions, such as asthma and allergic lung inflammation.05-10-2012
20120114645USE OF IL-1 ANTAGONISTS TO TREAT PSEUDOGOUT - Methods of treating, inhibiting, or ameliorating gout, including chronic active (refractory) gout, pseudogout, or drug-induced gout, in a human subject, are provided. The methods comprise administering to a subject in need thereof a therapeutic amount of an interleukin 1 (IL-1) antagonist, such as IL-1 trap rilonacept.05-10-2012
20120101035VEGF Antagonist Formulations - Formulations of a vascular endothelial growth factor (VEGF)-specific fusion protein antagonist are provided including a pre-lyophilized formulation, a reconstituted lyophilized formulation, and a stable liquid formulation. Preferably, the fusion protein has the sequence of SEQ ID NO:4.04-26-2012
20120100145METHODS FOR TREATING B-CELL LYMPHOMA BY ADMINISTERING AN ANTI-CD20 ANTIBODY - The present invention provides methods for treating a B-cell lymphoma in a human subject. The methods of the invention comprise administering to a subject in need thereof an antibody or antigen-binding fragment thereof that specifically binds human CD20. In certain embodiments, the methods of the invention are useful for treating non-Hodgkin's B-cell lymphoma.04-26-2012
20120097565Stabilized Formulations Containing Anti-Interleukin-4 Receptor (IL-4R) Antibodies - The present invention provides pharmaceutical formulations comprising a human antibody that specifically binds to human interleukin-4 receptor (hIL-4R). The formulations may contain, in addition to an anti-hIL-4R antibody, at least one amino acid, at least one sugar, or at least one non-ionic surfactant. The pharmaceutical formulations of the present invention exhibit a substantial degree of antibody stability after storage for several months.04-26-2012
20120096572Mice That Make VL Binding Proteins - Genetically modified mice and methods for making an using them are provided, wherein the mice comprise a replacement of all or substantially all immunoglobulin heavy chain V gene segments, D gene segments, and J gene segments with at least one light chain V gene segment and at least one light chain J gene segment. Mice that make binding proteins that comprise a light chain variable domain operably linked to a heavy chain constant region are provided. Binding proteins that contain an immunoglobulin light chain variable domain, including a somatically hypermutated light chain variable domain, fused with a heavy chain constant region, are provided. Modified cells, embryos, and mice that encode sequences for making the binding proteins are provided.04-19-2012
20120093824METHODS FOR TREATING PRURITUS BY ADMINISTERING AN ANTIBODY THAT SPECIFICALLY BINDS HUMAN PAR2 - The present invention provides methods for treating pruritus by blocking human protease activated receptor-2 (PAR2) activity. The methods of the invention can be used to treat pruritus associated with atopic dermatitis, psoriasis, burn scarring, hypertrophic scarring, keloids, renal failure or hepatic failure. The methods of the invention include administering an antibody or antigen-binding fragment thereof that specifically binds human PAR2.04-19-2012
20120087929VEGF Antagonist Formulations for Intravitreal Administration - Ophthalmic formulations of a vascular endothelial growth factor (VEGF)-specific fusion protein antagonist are provided suitable for intravitreal administration to the eye. The ophthalmic formulations include a stable liquid formulation and a lyophilizable formulation. Preferably, the protein antagonist has the amino acid sequence of residues 27-457 of SEQ ID NO:4.04-12-2012
20120083000Neuropeptide Release Assay For Sodium Channels - Methods and compositions for using genetically modified non-human animals are provided, wherein the genetic modification comprises a humanization of the one or more extracellular pore loops of a Na04-05-2012
20120076790ANTI-CD48 ANTIBODIES AND USES THEREOF - The present invention provides antibodies that bind to CD48 and methods of using same. According to certain embodiments of the invention, the antibodies are fully human antibodies that bind to human CD48. In certain embodiments, the antibodies of the present invention block the binding of CD48 to one or more CD48 receptor. The antibodies of the invention are useful, inter alia, for the treatment of diseases and disorders associated with one or more CD48 biological activities, including the treatment of allergic conditions and other inflammatory conditions.03-29-2012
20120073004Hybrid Light Chain Mice - Genetically modified mice are provided that express human λ variable (hVλ) sequences, including mice that express hVλ sequences from an endogenous mouse λ light chain locus, mice that express hVλ sequences from an endogenous mouse κ light chain locus, and mice that express hVλ sequences from a transgene or an episome wherein the hVλ sequence is linked to a mouse constant sequence. Mice are provided that are a source of somatically mutated human λ variable sequences useful for making antigen-binding proteins. Compositions and methods for making antigen-binding proteins that comprise human λ variable sequences, including human antibodies, are provided.03-22-2012
20120070861Human Lambda Light Chain Mice - Genetically modified mice are provided that express human λ variable (hVλ) sequences, including mice that express hVλ sequences from an endogenous mouse λ light chain locus, mice that express hVλ sequences from an endogenous mouse κ light chain locus, and mice that express hVλ sequences from a transgene or an episome wherein the hVλ sequence is linked to a mouse constant sequence. Mice are provided that are a source of somatically mutated human λ variable sequences useful for making antigen-binding proteins. Compositions and methods for making antigen-binding proteins that comprise human λ variable sequences, including human antibodies, are provided.03-22-2012
20120064621Cell Culture Compositions Capable of Producing a VEGF-Binding Fusion Polypeptide - The present invention provided cell culture compositions capable of producing fusion polypeptides that bind vascular endothelial growth factor (VEGF). The cell culture compositions of the invention comprise cells which contain an expression vector comprising a nucleic acid molecule encoding a fusion polypeptide that binds VEGF. The fusion polypeptides may comprise a VEGF receptor component having immunoglobulin-like (Ig) domain 2 of a first VEGF receptor, an Ig domain 3 of a second VEGF receptor, and a multimerizing component.03-15-2012
20120045440METHOD OF TREATING RHEUMATOID ARTHRITIS WITH AN ANTI-IL-6R ANTIBODY - The present invention provides methods of preventing or treating rheumatoid arthritis using a fully human antibody or antigen-binding fragment thereof that specifically binds human interleukin-6 receptor (hIL-6R). The methods of the present invention may include administration of a second therapeutic agent, such as one or more of a non-steroidal anti-inflammatory drug (NSAID), a glucocorticoid, a disease-modifying anti-rheumatic drug (DMARD), or a TNF-alpha antagonist, T-cell blocker, anti-CD20 antibody, an IL-1, JAK or IL-17 antagonist, or any combination thereof.02-23-2012
20120021409Common Light Chain Mouse - A genetically modified mouse is provided, wherein the mouse expresses an immunoglobulin light chain repertoire characterized by a limited number of light chain variable domains. Mice are provided that express just one or a few immunoglobulin light chain variable domains from a limited repertoire in their germline. Methods for making light chain variable regions in mice, including human light chain variable regions, are provided. Methods for making human variable regions suitable for use in multispecific binding proteins, e.g., bispecific antibodies, are provided.01-26-2012
20120014968STABILIZED FORMULATIONS CONTAINING ANTI-NGF ANTIBODIES - The present invention provides pharmaceutical formulations comprising a human antibody that specifically binds to human nerve growth factor (hNGF). The formulations may contain, in addition to an anti-hNGF antibody, at least one non-ionic surfactant, at least one sugar, and acetate. The pharmaceutical formulations of the present invention exhibit a substantial degree of antibody stability after storage for several months.01-19-2012
20120003697HIGH AFFINITY ANTIBODIES TO HUMAN IL-6 RECEPTOR - A human antibody or an antigen-binding fragment which binds human IL-6 receptor (hIL-6R) with a K01-05-2012
20110318342METHODS OF USING IL-1 ANTAGONISTS TO TREAT AUTOINFLAMMATORY DISEASE - Methods of treating, inhibiting, or ameliorating an autoinflammatory disorder, disease, or condition in a subject in need thereof, comprising administering to a subject in need a therapeutic amount of an interleukin 1 (IL-1) antagonist, wherein the autoinflammatory disorder, disease, or condition is treated, inhibited, or ameliorated. The IL-1 antagonist is a molecule capable of binding and inhibiting IL-1. The therapeutic methods are useful for treating a human adult or child suffering from Neonatal Onset Multisystem Inflammatory Disorder (NOMID/CINCA), Muckle-Wells Syndrome (MWS), Familial Cold Autoinflammatory Syndrome (FCAS), familial mediterranean fever (FMF), tumor necrosis factor receptor-associated periodic fever syndrome (TRAPS), or systemic onset juvenile idiopathic arthritis (Still's Disease).12-29-2011
20110311537METHODS OF USING IL-1 ANTAGONISTS TO TREAT FAMILIAL MEDITERRANEAN FEVER (FMF) - Methods of treating, inhibiting, or ameliorating Familial Mediterranean Fever (FMF) by administering to a subject in need thereof a therapeutically effective amount of an interleukin 1 (IL-1) antagonist, are provided. The IL-1 antagonist can be an antibody or derivative thereof, which is capable of blocking or inhibiting the biological action of IL-1, thereby treating, inhibiting or ameliorating FMF. Also provided are methods of treating, inhibiting, or ameliorating FMF by administering a therapeutically effective amount of an IL-1 antagonist in combination with additional therapeutic agents, including IL-1-specific fusion proteins, TNF inhibitors, NSAIDs, steroids, and the like.12-22-2011
20110307968PRODUCTION OF FERTILE XY ANIMALS FROM XY ES CELLS - Methods and compositions are described for making phenotypically female fertile animals from XY donor cells and suitable host embryos. Culture media and methods are provided for maintaining XY donor cells in culture that after introduction into a host embryo and gestation in a suitable host will result in fertile XY female animals. Methods and compositions are described for making fertile female animals in an F0 generation from a donor XY cell and a host embryo, as are methods for making F1 progeny that are homozygous for a modification from a heterozygous F0 fertile male and a heterozygous F0 fertile female sibling.12-15-2011
20110307966Mice Expressing Human Voltage-Gated Sodium Channels - Genetically modified non-human animals and methods and compositions for making and using them are provided, wherein the genetic modification comprises a humanization of an extracellular loop of an endogenous Na12-15-2011
20110293630Antibodies to Human GDF8 - The present invention provides isolated human or humanized antibodies or antigen-binding fragments thereof which specifically bind to Growth and Differentiation Factor-8 (GDF8) and block GDF8 activity. The antibodies and antibody fragments of the present invention may be used in therapeutic methods for treating conditions or disorders which are ameliorated or improved by inhibition of GDF8.12-01-2011
20110283376Methods of Modifying Eukaryotic Cells - A method for engineering and utilizing large DNA vectors to target, via homologous recombination, and modify, in any desirable fashion, endogenous genes and chromosomal loci in eukaryotic cells. These large DNA targeting vectors for eukaryotic cells, termed LTVECs, are derived from fragments of cloned genomic DNA larger than those typically used by other approaches intended to perform homologous targeting in eukaryotic cells. Also provided is a rapid and convenient method of detecting eukaryotic cells in which the LTVEC has correctly targeted and modified the desired endogenous gene(s) or chromosomal locus (loci) as well as the use of these cells to generate organisms bearing the genetic modification.11-17-2011
20110269187High Affinity Human Antibodies to Human IL-18 Receptor - An isolated antibody or antibody fragment that binds human interleukin-18 receptor alpha (hIL-18Rα), comprising a light chain variable region (LCVR) selected from the group consisting of SEQ ID NO: 5, 9, 13, 17, 21, 25, 29, 33, 37, 41, 45, 49, 53, 61, 65, 69, 73, 77, and 81 and/or a heavy chain variable region (HCVR) selected from the group consisting of SEQ ID NO: 3, 7, 11, 15, 19, 23, 27, 31, 35, 39, 43, 47, 51, 55, 59, 63, 67, 71, 75, and 79, or a fragment or sequence modified by an amino acid substitution, deletion or addition thereof.11-03-2011
20110258710Methods of Modifying Eukaryotic Cells - A method for engineering and utilizing large DNA vectors to target, via homologous recombination, and modify, in any desirable fashion, endogenous genes and chromosomal loci in eukaryotic cells. These large DNA targeting vectors for eukaryotic cells, termed LTVECs, are derived from fragments of cloned genomic DNA larger than those typically used by other approaches intended to perform homologous targeting in eukaryotic cells. Also provided is a rapid and convenient method of detecting eukaryotic cells in which the LTVEC has correctly targeted and modified the desired endogenous gene(s) or chromosomal locus (loci) as well as the use of these cells to generate organisms bearing the genetic modification.10-20-2011
20110257601VEGF ANTAGONIST FORMULATIONS FOR INTRAVITREAL ADMINISTRATION - Ophthalmic formulations of a vascular endothelial growth factor (VEGF)-specific fusion protein antagonist are provided suitable for intravitreal administration to the eye. The ophthalmic formulations include a stable liquid formulation and a lyophilizable formulation. Preferably, the protein antagonist has the amino acid sequence shown in SEQ ID NO:4.10-20-2011
20110256587HIGH AFFINITY HUMAN ANTIBODIES TO HUMAN NERVE GROWTH FACTOR - A human antibody or antigen-binding fragment of an antibody which specifically binds human nerve growth factor (NGF) with K10-20-2011
20110256556Humanized FcgR Mice - Genetically modified non-human animals and methods and compositions for making and using them are provided, wherein the genetic modification comprises a deletion of the endogenous low affinity FcγR locus, and wherein the mouse is capable of expressing a functional FcRγ-chain. Genetically modified mice are described, including mice that express low affinity human FcγR genes from the endogenous FcγR locus, and wherein the mice comprise a functional FcRγ-chain. Genetically modified mice that express up to five low affinity human FcγR genes on accessory cells of the host immune system are provided.10-20-2011
20110256148Methods for Treating Hypercholesterolemia Using Antibodies to PCSK9 - The present invention provides methods for treating hypercholesterolemia. The methods of the present invention comprise administering to a subject in need thereof a therapeutic composition comprising an anti-PCSK9 antibody or antigen-binding fragment thereof.10-20-2011
20110200982GENETICALLY MODIFIED MICE AND ENGRAFTMENT - A mouse with a humanization of the mIL-3 gene and the mGM-CSF gene, a knockout of a mRAG gene, and a knockout of a mIl2rg subunit gene; and optionally a humanization of the TPO gene is described. A RAG/Il2rg KO/hTPO knock-in mouse is described. A mouse engrafted with human hematopoietic stem cells (HSCs) that maintains a human immune cell (HIC) population derived from the HSCs and that is infectable by a human pathogen, e.g., 08-18-2011
20110195454Common Light Chain Mouse - A genetically modified mouse is provided, wherein the mouse is incapable of rearranging and expressing an endogenous mouse immunoglobulin light chain variable sequence, wherein the mouse expresses only one or two human light chain variable domains encoded by human immunoglobulin sequences operably linked to the mouse kappa (κ) constant gene at the endogenous mouse κ locus, wherein the mouse expresses a reverse chimeric antibody having a light chain variable domain derived from one of only two human light chain variable region gene segments and a mouse κ constant domain, and a human heavy chain variable domain and a mouse heavy chain constant domain, from an endogenous mouse heavy chain locus. Bispecific epitope-binding proteins that are fully human are provided, comprising two different heavy chains that associate with an identical light chain that comprises a variable domain derived from one of two different human light chain variable region gene segments.08-11-2011
20110189200METHODS OF TREATING AUTOIMMUNE DISEASES WITH DLL4 ANTAGONISTS - The present invention provides methods of treating a disease or disorder, in which increasing the number of regulatory T cell (Treg) is beneficial, by administering to a subject suffering from such a disease or disorder a therapeutically effective amount of DII4 antagonists that block DII4-Notch signal pathways, thereby increasing the number of Treg. Diseases or disorders treatable by the methods of the invention include autoimmune diseases or disorders, such as multiple sclerosis (MS), diabetes, and the like. Suitable DII4 antagonists for the invention include antibodies or antibody fragments that specifically bind DII4 and block DII4-Notch interactions, the extracellular domain of DII4, and the like. The invention also provides methods of preventing an occurrence or recurrence of such diseases or disorders in a subject predisposed or susceptible to developing such diseases or disorders. Furthermore, the methods of the invention are useful in preventing or treating organ transplant rejections or graft-versus-host disease.08-04-2011
20110189176METHODS OF TREATING DISEASES WITH DLL4 ANTAGONISTS - The present invention provides methods of preventing, treating or ameliorating diabetes by administering to a subject in need thereof a therapeutically effective amount of Dll4 antagonists that block Dll4-Notch signal pathways. As observed in a mouse model of diabetes, Dll4 antagonists exhibit protective effects on pancreatic islets, lower blood glucose levels, and block the production of auto-antibodies, including those against insulin and glutamic acid decarboxylase 65 (GAD65), via the expansion of regulatory T cells (Tregs). Thus, the present invention further provides methods of lowering the levels of blood glucose, and/or reducing or blocking the production of auto-antibodies, by administering to a subject in need thereof a therapeutically effective amount of Dll4 antagonists. Suitable Dll4 antagonists for the invention include antibodies or antibody fragments that specifically bind Dll4 and block Dll4-Notch interactions, the extracellular domain of Dll4, and the like.08-04-2011
20110171241Stabilized Formulations Containing Anti-Interleukin-6 (IL-6) Antibodies - The present invention provides pharmaceutical formulations comprising a human antibody that specifically binds to human interleukin-6 receptor (hIL-6R). The formulations may contain, in addition to an anti-hIL-6R antibody, at least one amino acid, at least one sugar, and/or at least one non-ionic surfactant. The pharmaceutical formulations of the present invention exhibit a substantial degree of antibody stability after storage for several months.07-14-2011
20110165650Fusion Polypeptides Capable of Activating Receptors - A fusion polypeptide comprising (A)07-07-2011
20110159015HUMAN ANTIBODIES TO HUMAN ANGIOPOIETIN-LIKE PROTEIN 4 - A fully human antibody or antigen-binding fragment of a human antibody that specifically binds and inhibits human angiopoietin-like protein 4 (hANGPTL4) is provided. The human anti-hANGPTL4 antibodies are useful in treating diseases or disorders associated with ANGPTL4, such as hyperlipidemia, hyperlipoproteinemia and dyslipidemia, including hypertriglyceridemia, hypercholesterolemia, chylomicronemia, and so forth. Furthermore, the anti-hANGPTL4 antibodies can be administered to a subject in need thereof to prevent or treat diseases or disorders, for which abnormal lipid metabolism is a risk factor. Such diseases or disorders include cardiovascular diseases, such as atherosclerosis and coronary artery diseases; acute pancreatitis; nonalcoholic steatohepatitis (NASH); diabetes; obesity; and the like.06-30-2011
20110154512Humanized Fc gamma R Mice - Genetically modified non-human animals and methods and compositions for making and using them are provided, wherein the genetic modification comprises a deletion of the endogenous low affinity FcγR locus, and wherein the mouse is capable of expressing a functional FcRγ-chain. Genetically modified mice are described, including mice that express low affinity human FcγR genes from the endogenous FcγR locus, and wherein the mice comprise a functional FcRγ-chain. Genetically modified mice that express up to five low affinity human FcγR genes on accessory cells of the host immune system are provided.06-23-2011
20110150905HUMAN ANTIBODIES TO HUMAN DELTA LIKE LIGAND 4 - The present invention provides methods of treating, ameliorating, or inhibiting tumor growth, cancer, or pathological angiogenesis by administering to a subject in need thereof a human antibody or fragment thereof that specifically binds to human delta-like ligand 4 (hDll4) and blocks hDll4 binding to a Notch receptor. The anti-hDll4 antibody or fragment thereof of the present invention have a high affinity with the K06-23-2011
20110145937Mice That Make Heavy Chain Antibodies - Genetically modified non-human animals and methods and compositions for making and using them are provided, wherein the genetic modification comprises a deletion in an immunoglobulin constant region CH1 gene (optionally a deletion in a hinge region) of an IgG, IgA, IgD, and/or IgE, and wherein the mouse is capable of expressing a functional IgM. Genetically modified mice are described, including mice having a functional IgM gene and modified to have a deletion of a CH1 domain and a hinge region in a heavy chain constant domain that is not an IgM, e.g., in an IgG heavy chain constant domain. Genetically modified mice that make human variable/mouse constant chimeric heavy chain antibodies (antibodies that lack a light chain), fully mouse heavy chain antibodies, or fully human heavy chain antibodies are provided.06-16-2011
20110104799Multifunctional Alleles - Nucleic acid constructs and methods for rendering modifications to a genome are provided, wherein the modifications comprise null alleles, conditional alleles and null alleles comprising COINs. Multifunctional alleles (MFA) are provided, as well as methods for making them, which afford the ability in a single targeting to introduce an allele that can be used to generate a null allele, a conditional allele, or an allele that is a null allele and that further includes a COIN. MFAs comprise pairs of cognate recombinase recognition sites, an actuating sequence and/or a drug selection cassette, and a nucleotide sequence of interest, and a COIN, wherein upon action of a recombinase a conditional allele with a COIN is formed. In a further embodiment, action of a second recombinase forms an allele that contains only a COIN in sense orientation. In a further embodiment, action by a third recombinase forms an allele that contains only the actuating sequence in sense orientation.05-05-2011
20110081681HUMAN ANTIBODIES TO HUMAN CD20 AND METHOD OF USING THEREOF - A human antibody or antigen-binding fragment of an antibody that specifically binds human CD20 and is capable of inducing complement dependent cytotoxicity (CDC), and is capable of increasing symptom free survival time between about 2-fold to about 9-fold or more, relative to control-treated animals in a mouse model of human lymphoma. The antibody or antigen-binding fragment thereof is useful in a therapeutic method for treating a CD20-mediated disease or condition, such as for example, non-Hodgkin's lymphoma, rheumatoid arthritis, systemic lupus erythematosus, Crohn's disease, chronic lymphocytic leukemia, and inflammatory diseases.04-07-2011
20110065902HIGH AFFINITY HUMAN ANTIBODIES TO PCSK9 - An human antibody or antigen-binding fragment of a human antibody that specifically binds and inhibits human proprotein convertase subtilisin/kexin type 9 (hPCSK9) characterized by the ability to reduce serum LDL cholesterol by 40-80% over a 24, 60 or 90 day period relative to predose levels, with little or no reduction in serum HDL cholesterol and/or with little or no measurable effect on liver function, as determined by ALT and AST measurements.03-17-2011
20110059095HIGH AFFINITY HUMAN ANTIBODIES TO HUMAN PROTEASE-ACTIVATED RECEPTOR-2 - The present invention provides antibodies that bind to protease-activated receptor-2 (PAR-2) and methods of using same. According to certain embodiments of the invention, the antibodies are fully human antibodies that bind to human PAR-2. The antibodies of the invention are useful, inter alia, for the treatment of diseases and disorders associated with one or more PAR-2 biological activities, including the treatment of pain conditions, inflammatory conditions and gastrointestinal conditions.03-10-2011
20110041197Promoter-Regulated Differentiation-Dependent Self-Deleting Cassette - Targeting constructs and methods of using them are provided for differentiation-dependent modification of nucleic acid sequences in cells and in non-human animals. Targeting constructs comprising a promoter operably linked to a recombinase are provided, wherein the promoter drives transcription of the recombinase in an differentiated cell but not an undifferentiated cell. Promoters include Blimp1, Prm1, Gata6, Gata4, Igf2, Lhx2, Lhx5, and Pax3. Targeting constructs with a cassette flanked on both sides by recombinase sites can be removed using a recombinase gene operably linked to a 3′-UTR that comprises a recognition site for an miRNA that is transcribed in undifferentiated cells but not in differentiated cells. The constructs may be included in targeting vectors, and can be used to automatically modify or excise a selection cassette from an ES cell, a non-human embryo, or a non-human animal.02-17-2011
20110041196miRNA-Regulated Differentiation-Dependent Self-Deleting Cassette - Targeting constructs and methods of using them are provided for differentiation-dependent modification of nucleic acid sequences in cells and in non-human animals. Targeting constructs comprising a promoter operably linked to a recombinase are provided, wherein the promoter drives transcription of the recombinase in an differentiated cell but not an undifferentiated cell. Promoters include Blimp1, Prm1, Gata6, Gata4, Igf2, Lhx2, Lhx5, and Pax3. Targeting constructs with a cassette flanked on both sides by recombinase sites can be removed using a recombinase gene operably linked to a 3′-UTR that comprises a recognition site for an miRNA that is transcribed in undifferentiated cells but not in differentiated cells. The constructs may be included in targeting vectors, and can be used to automatically modify or excise a selection cassette from an ES cell, a non-human embryo, or a non-human animal.02-17-2011
20110027286High Affinity Human Antibodies to Human Angiopoietin-2 - The present invention provides antibodies that bind to angiopoietin-2 (Ang-2) and methods of using same. According to certain embodiments of the invention, the antibodies are fully human antibodies that bind to human Ang-2. The antibodies of the invention are useful, inter alia, for the treatment of diseases and disorders associated with one or more Ang-2 biological activities including angiogenesis.02-03-2011
20110020342IGF-1 FUSION POLYPEPTIDES AND THERAPEUTIC USES THEREOF - A fusion protein comprising at least one IGF1 variant component and a fusion component (F), and, optionally, a signal sequence, exhibits improved stability relative to the native IGF1 or IGF2 polypeptide. The fusion component (F) may be a multimerizing component, such as an immunoglobulin domain, in particular, the Fc domain of IgG or a heavy chain of IgG. IGF1 variants were shown to have improved ability to increase muscle mass in a subject suffering from muscle atrophy caused by cachexia, immobilization, aging, chronic disease, cancer, hereditary condition, an atrophy-causing agent, and the like. IGF1 variants are also effective in decreasing blood glucose in a subject suffering from diabetes or hyperglycemia.01-27-2011
20110014208Method of Treating Osteoarthritis with an Antibody to NGF - Methods are disclosed for treating osteoarthritis in a human subject in need thereof, comprising administering to the subject a therapeutically effective amount of an anti-human NGF antibody, or antigen-binding fragment thereof, wherein at least one symptom associated with osteoarthritis is prevented, ameliorated or improved.01-20-2011
20110008374Use of IL-1 Antagonists to Treat Gout - Methods of treating, inhibiting, or ameliorating gout, including chronic acute (refractory) gout, pseudogout, or drug-induced gout, in a human subject in need thereof, comprising administering to a subject in need a therapeutic amount of an interleukin 1 (IL-1) antagonist, wherein the incidence of a gout flare is reduced or inhibited.01-13-2011
20100331527Readily Isolated Bispecific Antibodies with Native Immunoglobulin Format - A bispecific antibody format providing ease of isolation is provided, comprising immunoglobulin heavy chain variable domains that are differentially modified in the CH3 domain, wherein the differential modifications are non-immunogenic or substantially non-immunogenic with respect to the CH3 modifications, and at least one of the modifications results in a differential affinity for the bispecific antibody for an affinity reagent such as Protein A, and the bispecific antibody is isolable from a disrupted cell, from medium, or from a mixture of antibodies based on its affinity for Protein A.12-30-2010
20100330106Method of Treating Cancer with DLL4 Antagonist and Chemotherapeutic Agent - The invention provides methods for treating various types of cancer/tumor by administering the combination of DII4 antagonists, in particular, DII4 antibodies and fragments thereof that specifically bind human DII4, and chemotherapeutic agents. Such combination therapies exhibit synergistic effects compared to the treatment with either agent alone. Thus, the methods of the invention are particularly beneficial for cancer patients who have low tolerance to the side effects caused by high dosages required for the treatment by either agent alone, by being able to reduce effective dosages. Pharmaceutical compositions and kits containing DII4 antagonists and chemotherapeutic agents are also provided.12-30-2010
20100316636Method of Treating Rheumatoid Arthritis with an IL-6R Antibody - The present invention provides methods of preventing or treating rheumatoid arthritis using a fully human antibody or antigen-binding fragment thereof that specifically binds human interleukin-6 receptor (hIL-6R). The methods of the present invention may include administration of a second therapeutic agent, such as one or more of a non-steroidal anti-inflammatory drug (NSAID), a glucocorticoid, a disease-modifying anti-rheumatic drug (DMARD), or a TNF-alpha antagonist, T-cell blocker, anti-CD20 antibody, an IL-1, JAK or IL-17 antagonist, or any combination thereof.12-16-2010
20100316627Human antibodies to human IL-6 receptor - A human antibody or an antigen-binding fragment which binds human IL-6 receptor (hIL-6R) with a K12-16-2010
20100304436Fucosylation-Deficient Cells - An isolated nucleic acid encoding an FX protein having a serine at position 12-02-2010
20100291626ENHANCED EXPRESSION AND STABILITY REGIONS - Expression-enhancing nucleotide sequences for expression in eukaryotic systems are provided that allow for enhanced and stable expression of recombinant proteins in eukaryotic cells. Enhanced expression and stability regions (EESYRs) are provided for expression of a gene of interest in a eukaryotic cell. Chromosomal loci, sequences, and vectors are provided for enhanced and stable expression of genes in eukaryotic cells.11-18-2010
20100291107HIGH AFFINITY HUMAN ANTIBODIES TO HUMAN IL-4 RECEPTOR - The present invention provides methods for treating one or more diseases or disorders which are improved, inhibited or ameliorated by reducing interleukin-4 (IL-4) activity. The methods of the invention comprise administering to a patient an antibody, or antigen-binding fragment thereof, which specifically binds to a human IL-4 receptor.11-18-2010
20100279933VEGF ANTAGONIST FORMULATIONS - Formulations of a vascular endothelial growth factor (VEGF)-specific fusion protein antagonist are provided including a pre-lyophilized formulation, a reconstituted lyophilized formulation, and a stable liquid formulation. Preferably, the fusion protein has the sequence of SEQ ID NO:4.11-04-2010
20100233803Fusion Polypeptides Capable of Activating Receptors - A fusion polypeptide comprising (A)09-16-2010
20100221782Modified Chimeric Polypeptides With Improved Pharmacokinetic Properties - Modified chimeric polypeptides with improved pharmacokinetics are disclosed. Specifically, modified chimeric Flt1 receptor polypeptides that have been modified in such a way as to improve their pharmacokinetic profile are disclosed. Also disclosed are methods of making and using the modified polypeptides including but not limited to using the modified polypeptides to decrease or inhibit plasma leakage and/or vascular permeability in a mammal.09-02-2010
20100166768High Affinity Human Antibodies to PCSK9 - An human antibody or antigen-binding fragment of a human antibody that specifically binds and inhibits human proprotein convertase subtilisin/kexin type 9 (hPCSK9) characterized by the ability to reduce serum LDL cholesterol by 40-80% over a 24, 60 or 90 day period relative to predose levels, with little or no reduction in serum HDL cholesterol and/or with little or no measurable effect on liver function, as determined by ALT and AST measurements.07-01-2010
20100129817IDENTIFYING GERMLINE COMPETENT EMBRYONIC STEM CELLS - Methods and compositions for selecting ES cells that are germline competent are provided, including gene expression arrays of from one to about 300 or more genes. Selecting ES cells that are competent for germline transmission by comparing the expression of one or more genes between an ES cell that is competent at germline transmission with an ES cell of interest is described. Selecting ES cells likely to be competent at germline transmission, based on their level of expression of gtl2, is also described.05-27-2010
20100111921Use of IL-1 Antagonists to Treat Gout - Methods of treating, inhibiting, or ameliorating gout, including chronic acute (refractory) gout, pseudogout, or drug-induced gout, in a human subject in need thereof, comprising administering to a subject in need a therapeutic amount of an interleukin 1 (IL-1) antagonist, wherein the incidence of a gout flare is reduced or inhibited.05-06-2010
20100087632VEGF-Binding Fusion Proteins and Therapeutic Uses Thereof - Fusion proteins which bind and inhibit vascular endothelial growth factor (VEGF). The VEGF-binding fusion proteins are therapeutically useful for treating VEGF-associated conditions and diseases, and are specifically designed for local administration to specific organs, tissues, and/or cells.04-08-2010
20100075903Lyophilized VEGF Antagonist Formulations for Intravitreal Administration - Ophthalmic formulations of a vascular endothelial growth factor (VEGF)-specific fusion protein antagonist are provided suitable for intravitreal administration to the eye. The ophthalmic formulations include a stable liquid formulation and a lyophilizable formulation. Preferably, the protein antagonist has the amino acid sequence shown in SEQ ID NO:4.03-25-2010
20100047254High Affinity Human Antibodies to Human IL-4 Receptor - The present invention provides methods for treating one or more diseases or disorders which are improved, inhibited or ameliorated by reducing interleukin-4 (IL-4) activity. The methods of the invention comprise administering to a patient an antibody, or antigen-binding fragment thereof, which specifically binds to a human IL-4 receptor.02-25-2010
20100042330Non-Hypergeometric Overlap Probability - Methods, software, and systems are provided for determining the probability of an overlap set of entities having an overlap size, where the overlap set is independently selected from two sets of non-identical entities. Applications of the invention to microarrays are provided. Probability distributions are provided for determining the probability that the size of an overlap gene set from two different microarrays occurs by chance. Microarray analysis for determining the size of a statistically significant overlap gene set given two different microarrays is described. Overlap set size probability determinations that account for the total number of genes in two different microarrays and not just the common genes are described.02-18-2010
20100034833HIGH AFFINITY HUMAN ANTIBODIES TO HUMAN IL-18 RECEPTOR - An isolated antibody or antibody fragment that binds human interleukin-18 receptor alpha (hIL-18Rα), comprising a light chain variable region (LCVR) selected from the group consisting of SEQ ID NO: 5, 9, 13, 17, 21, 25, 29, 33, 37, 41, 45, 49, 53, 61, 65, 69, 73, 77, and 81 and/or a heavy chain variable region (HCVR) selected from the group consisting of SEQ ID NO: 3, 7, 11, 15, 19, 23, 27, 31, 35, 39, 43, 47, 51, 55, 59, 63, 67, 71, 75, and 79, or a fragment or sequence modified by an amino acid substitution, deletion or addition thereof.02-11-2010
20100021476High Affinity Human Antibodies to Human IL-4 Receptor - The present invention provides methods for treating one or more diseases or disorders which are improved, inhibited or ameliorated by reducing interleukin-4 (IL-4) activity. The methods of the invention comprise administering to a patient an antibody, or antigen-binding fragment thereof, which specifically binds to a human IL-4 receptor.01-28-2010
20090285841ANTITUMOR COMBINATIONS CONTAINING A VEGF-INHIBITING AGENT AND 5FU OR A DERIVATIVE THEREOF - This invention relates to antitumor combinations comprising a VEGF inhibitor combined with 5-fluorouracil or with a 5-fluoropyrimidine derivative that are therapeutically useful in the treatment of neoplastic diseases, and pharmaceutical compositions comprising such combinations.11-19-2009
20090271884ES Cell-Derived Mice From Diploid Host Embryo Injection - Genetically modified mice and nucleic acid constructs for making the genetically modified mice are described. A first mouse having a gene encoding an activator (such as a Cre recombinase) operably linked to a developmentally-regulated promoter (such as a Nanog promoter) is provided. A second mouse having a toxic responder gene (such as a gene encoding diphtheria toxin A) is provided, where the toxic gene is expressed only in the presence of an activator, Embryos from a mating of the first and the second mouse are provided as host embryos suitable for generating mice from donor cells introduced into the host embryos. Ablating the ICM of a mouse embryo physically, chemically, or genetically is described, as well as making F0 generation mice that are substantially or in full derived from donor cells, employing a host mouse embryo with an ablated or nonproliferating ICM.10-29-2009
20090246199THERAPEUTIC METHODS FOR INHIBITING TUMOR GROWTH WITH DLL4 ANTAGONISTS - Disclosed is a therapeutic method for inhibiting development or growth of tumors that are resistant to the blockade of delta-like ligand 4 (Dll4), or vascular endothelial growth factor (VEGF), or to other therapeutic agents, by administering the combination of Dll4 antagonist and VEGF antagonist. The combined administration of these two agents, concurrently or sequentially, exhibits synergistic effects on blood vessel development and growth, thereby more effectively inhibiting the tumor growth than an administration of either agent alone. The Dll4 antagonist can be an anti-Dll4 antibody or antibody fragment capable of inhibiting the binding of Dll4 to a Notch receptor, or a fusion protein comprising the extracellular domain of Dll4 or a soluble Notch receptor, or a fragment thereof, fused to a multimerizing component. The VEGF antagonist can be a VEGF trap, anti-VEGF antibody or antibody fragment capable of inhibiting the binding of VEGF to a VEGF receptor.10-01-2009
20090175864IGF-1 AND IGF-2 CHIMERIC POLYPEPTIDES AND THERAPEUTIC USES THEREOF - Pharmaceutical compositions containing a chimeric protein comprising an IGF1 and an IGF2 component and optionally (F), a fusion component, and/or a signal sequence, are provided. The chimeric protein exhibits improved activity relative to the native IGF1 or IGF2 polypeptide. Further, therapeutic methods for treating IGF1 insufficiency diseases or conditions using the pharmaceutical compositions of the invention are also provided. The diseases or conditions treatable with the methods include muscle atrophy as a result of, for example, aging, cachexia, rheumatoid arthritis, diabetes, disuse or immobilization of muscle, and the like, as well as dwarfism and myocardial infarction.07-09-2009
20090162901Inducible Eukaryotic Expression System - Compositions and methods for the inducible expression of genes in eukaryotic cells are provided. Expression of a nucleotide sequence of interest encoding a protein of interest is controlled by a regulatory fusion protein that consists of a transcription blocking domain and a ligand-binding domain. When a cognate ligand for the ligand-binding domain is present, transcription of the nucleotide sequence of interest is blocked. Upon removal of the cognate ligand, the nucleotide sequence of interest is transcribed. The method is useful for large scale bioreactor production of a desired protein of interest in eukaryotic cells.06-25-2009
20090156492Methods of Using IL-1 Antagonists to Treat Autoinflammatory Disease - Methods of treating, inhibiting, or ameliorating an autoinflammatory disorder, disease, or condition in a subject in need thereof, comprising administering to a subject in need a therapeutic amount of an interleukin 1 (IL-1) antagonist, wherein the autoinflammatory disorder, disease, or condition is treated, inhibited, or ameliorated. The IL-1 antagonist is an IL-1 trap, preferably comprising a sequence selected from the group consisting of SEQ ID NO: 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, or a substantially identical having at least 95% identity to the sequence shown in SEQ ID NO: 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26 and capable of binding and inhibiting IL-1. The therapeutic methods are useful for treating a human adult or child suffering from Neonatal Onset Multisystem Inflammatory Disorder (NOMID/CINCA), Muckle-Wells Syndrome (MWS), Familial Cold Autoinflammatory Syndrome (FCAS), familial mediterranean fever (FMF), or systemic onset juvenile rheumatoid arthritis (Still's Disease).06-18-2009
20090155899Modified Chimeric Polypeptides with Improved Pharmacokinetic Properties - Modified chimeric polypeptides with improved pharmacokinetics are disclosed. Specifically, modified chimeric Flt1 receptor polypeptides that have been modified in such a way as to improve their pharmacokinetic profile are disclosed. Also disclosed are methods of making and using the modified polypeptides including but not limited to using the modified polypeptides to decrease or inhibit plasma leakage and/or vascular permeability in a mammal.06-18-2009
20090142354HUMAN ANTIBODIES TO HUMAN DELTA LIKE LIGAND 4 - An isolated human antibody or a fragment of a human antibody which specifically binds to human delta-like ligand 4 (hDll4) and blocks hDll4 binding to a Notch receptor. The human anti-hDll4 antibody or antibody fragment binds dimeric hDll4 with an affinity of 75 pM or better, as measured by surface plasmon resonance.06-04-2009
20090137416Isolating Cells Expressing Secreted Proteins - A method of detecting and isolating cells that produce a secreted protein of interest (POI) that has a T cell receptor variable domain, comprising: a) constructing a cell line transiently or stably expressing a cell surface capture molecule, which binds the POI, by transfecting the cell line with a nucleic acid that encodes such cell surface capture molecule; b) transfecting said cell simultaneously or subsequently with a second nucleic acid that encodes a POI wherein such POI is secreted; c) detecting the surface-displayed POI by contacting the cells with a detection molecule, which binds the POI; and d) isolating cells based on the detection molecule.05-28-2009
20090124005Enhanced Expression and Stability Regions - Expression-enhancing nucleotide sequences for expression in eukaryotic systems are provided that allow for enhanced and stable expression of recombinant proteins in eukaryotic cells. Enhanced expression and stability regions (EESYRs) are provided for expression of a gene of interest in a eukaryotic cell. Chromosomal loci, sequences, and vectors are provided for enhanced and stable expression of genes in eukaryotic cells.05-14-2009
20090123446Use of IL-1 Antagonists to Treat Gout - Methods of treating, inhibiting, or ameliorating gout, including chronic acute (refractory) gout, pseudogout, or drug-induced gout, in a human subject in need thereof, comprising administering to a subject in need a therapeutic amount of an interleukin 1 (IL-1) antagonist, wherein the incidence of a gout flare is reduced or inhibited.05-14-2009
20090081217Modified Chimeric Polypeptides with Improved Pharmacokinetic Properties - Modified chimeric polypeptides with improved pharmacokinetics are disclosed. Specifically, modified chimeric Flt1 receptor polypeptides that have been modified in such a way as to improve their pharmacokinetic profile are disclosed. Also disclosed are methods of making and using the modified polypeptides including but not limited to using the modified polypeptides to decrease or inhibit plasma leakage and/or vascular permeability in a mammal.03-26-2009
20090074793High Affinity Human Antibodies to Human IL-4 Receptor - An isolated human antibody or antibody fragment thereof which binds to human interleukin-4 receptor alpha (hIL-4Rα) with high affinity (K03-19-2009
20090062200VEGF-Binding Fusion Proteins and Therapeutic Uses Thereof - Nucleic acid molecules encoding fusion proteins which bind and inhibit vascular endothelial growth factor (VEGF). The VEGF-binding fusion proteins are therapeutically useful for treating VEGF-associated conditions and diseases, and are specifically designed for local administration to specific organs, tissues, and/or cells.03-05-2009
20090041717HIGH AFFINITY HUMAN ANTIBODIES TO HUMAN NERVE GROWTH FACTOR - A human antibody or antigen-binding fragment of an antibody which specifically binds human nerve growth factor (NGF) with K02-12-2009
20090035322Human Antibodies to Human CD20 and Method of Using Thereof - A human antibody or antigen-binding fragment of an antibody that specifically binds human CD20 and is capable of inducing complement dependent cytotoxicity (CDC), and is capable of increasing symptom free survival time between about 2-fold to about 9-fold or more, relative to control-treated animals in a mouse model of human lymphoma. The antibody or antigen-binding fragment thereof is useful in a therapeutic method for treating a CD20-mediated disease or condition, such as for example, non-Hodgkin's lymphoma, rheumatoid arthritis, systemic lupus erythematosus, Crohn's disease, chronic lymphocytic leukemia, and inflammatory diseases.02-05-2009
20090017035HUMAN ANTIBODIES TO HUMAN DELTA LIKE LIGAND 4 - An isolated human antibody or a fragment of a human antibody which specifically binds to human delta-like ligand 4 (hDll4) and blocks hDll4 binding to a Notch receptor. The human anti-hDll4 antibody or antibody fragment binds hDll4 with an affinity of 300 pM or better, as measured by surface plasmon resonance.01-15-2009
20080220004Use of VEGF inhibitors for treatment of eye disorders - Modified chimeric polypeptides with improved pharmacokinetics and improved tissue penetration are disclosed useful for treating eye disorders, including age-related macular degeneration and diabetic retinopathy.09-11-2008

Patent applications by Regeneron Pharmaceuticals, Inc.