US20040033228A1 - Formulation of human antibodies for treating TNF-alpha associated disorders - Google Patents
Formulation of human antibodies for treating TNF-alpha associated disorders Download PDFInfo
- Publication number
- US20040033228A1 US20040033228A1 US10/222,140 US22214002A US2004033228A1 US 20040033228 A1 US20040033228 A1 US 20040033228A1 US 22214002 A US22214002 A US 22214002A US 2004033228 A1 US2004033228 A1 US 2004033228A1
- Authority
- US
- United States
- Prior art keywords
- antibody
- formulation
- tnfα
- seq
- antigen
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Abandoned
Links
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/395—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
- A61K39/39591—Stabilisation, fragmentation
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/395—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/395—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
- A61K39/39533—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum against materials from animals
- A61K39/3955—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum against materials from animals against proteinaceous materials, e.g. enzymes, hormones, lymphokines
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/02—Inorganic compounds
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
- A61K47/10—Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
- A61K47/12—Carboxylic acids; Salts or anhydrides thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/22—Heterocyclic compounds, e.g. ascorbic acid, tocopherol or pyrrolidones
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/26—Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/19—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles lyophilised, i.e. freeze-dried, solutions or dispersions
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/02—Stomatological preparations, e.g. drugs for caries, aphtae, periodontitis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/04—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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/18—Drugs for disorders of the alimentary tract or the digestive system for pancreatic disorders, e.g. pancreatic enzymes
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/06—Antiasthmatics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/12—Drugs for disorders of the urinary system of the kidneys
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/06—Antipsoriatics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/04—Drugs for skeletal disorders for non-specific disorders of the connective tissue
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/06—Antigout agents, e.g. antihyperuricemic or uricosuric agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/02—Drugs for disorders of the nervous system for peripheral neuropathies
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/04—Centrally acting analgesics, e.g. opioids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/04—Anorexiants; Antiobesity agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
- A61P31/14—Antivirals for RNA viruses
- A61P31/18—Antivirals for RNA viruses for HIV
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P33/00—Antiparasitic agents
- A61P33/02—Antiprotozoals, e.g. for leishmaniasis, trichomoniasis, toxoplasmosis
- A61P33/06—Antimalarials
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
- A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/08—Antiallergic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/04—Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
- C07K16/24—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against cytokines, lymphokines or interferons
- C07K16/241—Tumor Necrosis Factors
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K2039/505—Medicinal preparations containing antigens or antibodies comprising antibodies
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/20—Immunoglobulins specific features characterized by taxonomic origin
- C07K2317/21—Immunoglobulins specific features characterized by taxonomic origin from primates, e.g. man
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/70—Immunoglobulins specific features characterized by effect upon binding to a cell or to an antigen
- C07K2317/76—Antagonist effect on antigen, e.g. neutralization or inhibition of binding
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/90—Immunoglobulins specific features characterized by (pharmaco)kinetic aspects or by stability of the immunoglobulin
- C07K2317/92—Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/90—Immunoglobulins specific features characterized by (pharmaco)kinetic aspects or by stability of the immunoglobulin
- C07K2317/94—Stability, e.g. half-life, pH, temperature or enzyme-resistance
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
Definitions
- Tumor necrosis factor ⁇ is a cytokine produced by numerous cell types, including monocytes and macrophages, that was originally identified based on its capacity to induce the necrosis of certain mouse tumors (see e.g., Old, L. (1985) Science 230:630-632). Subsequently, a factor termed cachectin, associated with cachexia, was shown to be the same molecule as TNF ⁇ . TNF ⁇ has been implicated in mediating shock (see e.g., Beutler, B. and Cerami, A. (1988) Annu. Rev. Biochem. 57:505-518; Beutler, B. and Cerami, A. (1989) Annu. Rev. Immunol.
- TNF ⁇ has been implicated in the pathophysiology of a variety of other human diseases and disorders, including sepsis, infections, autoimmune diseases, transplant rejection and graft-versus-host disease (see e.g., Moeller, A., et al. (1990) Cytokine 2:162-169; U.S. Pat. No. 5,231,024 to Moeller et al.; European Patent Publication No. 260 610 B1 by Moeller, A., et al. Vasilli, P. (1992) Annu. Rev. Immunol. 10:411-452; Tracey, K. J. and Cerami, A. (1994) Annu. Rev. Med. 45:491-503).
- hTNF ⁇ human TNF ⁇
- therapeutic strategies have been designed to inhibit or counteract hTNF ⁇ activity.
- antibodies that bind to, and neutralize, hTNF ⁇ have been sought as a means to inhibit hTNF ⁇ activity.
- Some of the earliest of such antibodies were mouse monoclonal antibodies (mAbs), secreted by hybridomas prepared from lymphocytes of mice immunized with hTNF ⁇ (see e.g, Hahn T; et al., (1985) Proc Natl Acad Sci USA 82: 3814-3818; Liang, C-M., et al. (1986) Biochem. Biophys. Res. Commun.
- mouse anti-hTNF ⁇ antibodies often displayed high affinity for hTNF ⁇ (e.g., Kd ⁇ 10 ⁇ 9 M) and were able to neutralize hTNF ⁇ activity
- their use in vivo may be limited by problems associated with administration of mouse antibodies to humans, such as short serum half life, an inability to trigger certain human effector functions and elicitation of an unwanted immune response against the mouse antibody in a human (the “human anti-mouse antibody” (HAMA) reaction).
- HAMA human anti-mouse antibody
- murine anti-hTNF ⁇ antibodies have been genetically engineered to be more “human-like.”
- chimeric antibodies in which the variable regions of the antibody chains are murine-derived and the constant regions of the antibody chains are human-derived, have been prepared (Knight, D. M, et al. (1993) Mol. Immunol. 30:1443-1453; PCT Publication No. WO 92/16553 by Daddona, P. E., et al.).
- humanized antibodies in which the hypervariable domains of the antibody variable regions are murine-derived but the remainder of the variable regions and the antibody constant regions are human-derived, have also been prepared (PCT Publication No. WO 92/11383 by Adair, J. R., et al.).
- HACA human anti-chimeric antibody
- these chimeric and humanized antibodies still retain some murine sequences, they still may elicit an unwanted immune reaction, the human anti-chimeric antibody (HACA) reaction, especially when administered for prolonged periods, e.g., for chronic indications, such as rheumatoid arthritis (see e.g., Elliott, M. J., et al. (1994) Lancet 344:1125-1127; Elliot, M. J., et al. (1994) Lancet 344:1105-1110).
- a preferred hTNF ⁇ inhibitory agent to murine mAbs or derivatives thereof would be an entirely human anti-hTNF ⁇ antibody, since such an agent should not elicit the HAMA reaction, even if used for prolonged periods.
- Human monoclonal autoantibodies against hTNF ⁇ have been prepared using human hybridoma techniques (Boyle, P., et al. (1993) Cell. Immunol. 152:556-568; Boyle, P., et al. (1993) Cell. Immunol. 152:569-581; European Patent Application Publication No. 614 984 A2 by Boyle, et al.).
- a stable aqueous pharmaceutical formulation with an extended shelf life comprising an antibody which is suitable for therapeutic use to inhibit or counteract detrimental hTNF ⁇ activity.
- a stable aqueous pharmaceutical formulation with an extended shelf life comprising an antibody suitable for therapeutic use which is easily administered and contains a high protein concentration.
- This invention provides a liquid aqueous pharmaceutical formulation consisting of a therapeutically effective amount of an antibody in a buffered solution forming a formulation having a pH between about 4 and about 8 and having a shelf life of at least 18 months.
- the invention also includes an aqueous pharmaceutical formulation comprising a therapeutically effective amount of an antibody in a buffered solution forming a formulation having a pH between about 4 and 8 and having a shelf life of at least 18 months in the liquid state.
- the pharmaceutical formulation has enhanced stability.
- the formulation of the invention is stable following at least 3 freeze/thaw cycles of the formulation.
- the antibody is directed to TNF ⁇ .
- the antibody is directed to human TNF ⁇ .
- the antibody is D2E7.
- This invention also provides a liquid aqueous pharmaceutical formulation comprising a therapeutically effective amount of an antibody in a buffered solution forming a formulation having a pH between 4 and 8 and having enhanced stability of at least 12 months at a temperature of 2-8° C. In one embodiment, the formulation has enhanced stability of at least 18 months.
- the antibody is directed to TNF ⁇ . In yet another embodiment, the antibody is directed to human TNF ⁇ . In a further embodiment, the antibody is D2E7.
- the invention further provides a liquid aqueous pharmaceutical formulation comprising a therapeutically effective amount of an antibody in a buffered solution forming a formulation having a pH between about 4 and about 8 which is easily administratable.
- the antibody is directed to TNF ⁇ .
- the antibody is directed to human TNF ⁇ .
- the antibody is D2E7.
- the liquid aqueous pharmaceutical formulation is suitable for injection.
- the formulation is suitable for single use sc injection.
- the concentration of the antibody in the liquid aqueous pharmaceutical formulation is about 1-150 mg/ml.
- the concentration of the antibody in the formulation is about 50 mg/ml.
- the formulation has a high protein concentration.
- the formulation is not light sensitive.
- the liquid aqueous pharmaceutical formulation contains an antibody, or an antigen-binding portion thereof, that dissociates from human TNF ⁇ with a K d of 1 ⁇ 10 ⁇ 8 M or less and a K off rate constant of 1 ⁇ 10 ⁇ 3 s ⁇ 1 or less, both determined by surface plasmon resonance, and neutralizes human TNF ⁇ cytotoxicity in a standard in vitro L929 assay with an IC 50 of 1 ⁇ 10 ⁇ 7 M or less.
- the formulation of the invention contains an antibody, or antigen-binding portion thereof, which dissociates from human TNF ⁇ with a K off rate constant of 5 ⁇ 10 ⁇ 4 s ⁇ 1 or less.
- the formulation contains an antibody, or antigen-binding portion thereof, which dissociates from human TNF ⁇ with a K off rate constant of 1 ⁇ 10 ⁇ 4 s ⁇ 1 or less.
- the formulation of the invention contains an antibody, or antigen-binding portion thereof, which neutralizes human TNF ⁇ cytotoxicity in a standard in vitro L929 assay with an IC 50 of 1 ⁇ 10 ⁇ 8 M or less.
- the claimed formulation includes an antibody, or antigen-binding portion thereof, which neutralizes human TNF ⁇ cytotoxicity in a standard in vitro L929 assay with an IC 50 of 1 ⁇ 10 ⁇ 9 M or less.
- Another embodiment of the invention includes a formulation where the antibody, or antigen-binding portion thereof, neutralizes human TNF ⁇ cytotoxicity in a standard in vitro L929 assay with an IC 50 of 1 ⁇ 10 ⁇ 10 M or less.
- the liquid aqueous pharmaceutical formulation contains of an antibody, or antigen-binding portion thereof, which is a recombinant antibody, or antigen-binding portion thereof.
- the formulation contains an antibody, or antigen-binding portion thereof, which inhibits human TNF ⁇ -induced expression of ELAM-1 on human umbilical vein endothelial cells.
- the claimed formulation includes the D2E7 antibody.
- the liquid aqueous pharmaceutical formulation includes an antibody, or antigen-binding portion, thereof which dissociates from human TNF ⁇ with a K off rate constant of 1 ⁇ 10 ⁇ 3 s ⁇ 1 or less, as determined by surface plasmon resonance;
- b) has a light chain CDR3 domain comprising the amino acid sequence of SEQ ID NO: 3, or modified from SEQ ID NO: 3 by a single alanine substitution at position 1, 4, 5, 7 or 8 or by one to five conservative amino acid substitutions at positions 1, 3, 4, 6, 7, 8 and/or 9;
- the formulation of the invention includes an antibody, or an antigen-binding portion thereof, which dissociates from human TNF ⁇ with a K off rate constant of 5 ⁇ 10 ⁇ 4 s ⁇ 1 or less.
- the formulation includes an antibody, or an antigen-binding portion thereof, which dissociates from human TNF ⁇ with a K off rate constant of 1 ⁇ 10 ⁇ 4 s ⁇ 1 or less.
- the liquid aqueous pharmaceutical formulation contains of an antibody, or antigen-binding portion thereof, which has a light chain variable region (LCVR) having a CDR3 domain comprising the amino acid sequence of SEQ ID NO: 3, or modified from SEQ ID NO: 3 by a single alanine substitution at position 1, 4, 5, 7 or 8, and with a heavy chain variable region (HCVR) having a CDR3 domain comprising the amino acid sequence of SEQ ID NO: 4, or modified from SEQ ID NO: 4 by a single alanine substitution at position 2, 3, 4, 5, 6, 8, 9, 10 or 11.
- LCVR light chain variable region
- HCVR heavy chain variable region
- the formulation of the invention contains an antibody, wherein the LCVR of the antibody, or an antigen-binding portion thereof, further has a CDR2 domain comprising the amino acid sequence of SEQ ID NO: 5 and the HCVR of the antibody, or an antigen-binding portion thereof, further has a CDR2 domain comprising the amino acid sequence of SEQ ID NO: 6.
- the formulation of the invention contains an antibody, wherein the LCVR of the antibody, or an antigen-binding portion thereof, further has CDR1 domain comprising the amino acid sequence of SEQ ID NO: 7 and the HCVR has a CDR1 domain comprising the amino acid sequence of SEQ ID NO: 8.
- the antibody or antigen-binding portion thereof, contained in the liquid aqueous pharmaceutical formulation has a light chain variable region (LCVR) comprising the amino acid sequence of SEQ ID NO: 1 and a heavy chain variable region (HCVR) comprising the amino acid sequence of SEQ ID NO: 2.
- LCVR light chain variable region
- HCVR heavy chain variable region
- the antibody, or antigen-binding portion thereof has an IgG1 heavy chain constant region.
- the antibody, or antigen-binding portion thereof has an IgG4 heavy chain constant region.
- the antibody, or antigen-binding portion thereof is a Fab fragment.
- the antibody, or antigen-binding portion thereof is a single chain Fv fragment.
- the liquid aqueous pharmaceutical formulation contains an antibody, or antigen-binding portion thereof, which has a light chain variable region (LCVR) having a CDR3 domain comprising an amino acid sequence selected from the group consisting of SEQ ID NO: 3, SEQ ID NO: 11, SEQ ID NO: 12, SEQ ID NO: 13, SEQ ID NO: 14, SEQ ID NO: 15, SEQ ID NO: 16, SEQ ID NO: 17, SEQ ID NO: 18, SEQ ID NO: 19, SEQ ID NO: 20, SEQ ID NO: 21, SEQ ID NO: 22, SEQ ID NO: 23, SEQ ID NO: 24, SEQ ID NO: 25, SEQ ID NO: 26 or with a heavy chain variable region (HCVR) having a CDR3 domain comprising an amino acid sequence selected from the group consisting of SEQ ID NO: 4, SEQ ID NO: 27, SEQ ID NO: 28, SEQ ID NO: 29, SEQ ID NO: 30, SEQ ID NO: 31, SEQ ID NO: 32, SEQ ID NO: 33 and SEQ ID NO: 34
- LCVR light chain variable region
- the antibody, or antigen-binding portion thereof neutralizes the activity of human TNF ⁇ , chimpanzee TNF ⁇ and at least one additional primate TNF ⁇ selected from the group consisting of baboon TNF ⁇ , marmoset TNF ⁇ , cynomolgus TNF ⁇ and rhesus TNF ⁇ .
- the formulation of the invention includes an antibody, or an antigen-binding portion thereof, which also neutralizes the activity of mouse TNF ⁇ .
- the formulation of the invention also an antibody, or an antigen-binding portion thereof, which neutralizes the activity of pig TNF ⁇ .
- the invention provides a liquid aqueous pharmaceutical formulation which contains an antibody, or antigen-binding portion thereof, which binds to human TNF ⁇ and comprises:
- a light chain CDR3 domain comprising the amino acid sequence of SEQ ID NO: 3, or modified from SEQ ID NO: 3 by a single alanine substitution at position 1, 4, 5, 7 or 8 or by one to five conservative amino acid substitutions at positions 1, 3, 4, 6, 7, 8 and/or 9, and
- a heavy chain CDR3 domain comprising the amino acid sequence of SEQ ID NO: 4, or modified from SEQ ID NO: 4 by a single alanine substitution at position 2, 3, 4, 5, 6, 8, 9, 10 or 11 or by one to five conservative amino acid substitutions at positions 2, 3, 4, 5, 6, 8, 9, 10, 11 and/or 12.
- the liquid aqueous pharmaceutical formulation includes an antibody which bind human TNF ⁇ and comprises a light chain variable region (LCVR) having a CDR3 domain comprising an amino acid sequence selected from the group consisting of SEQ ID NO: 3, SEQ ID NO: 11, SEQ ID NO: 12, SEQ ID NO: 13, SEQ ID NO: 14, SEQ ID NO: 15, SEQ ID NO: 16, SEQ ID NO: 17, SEQ ID NO: 18, SEQ ID NO: 19, SEQ ID NO: 20, SEQ ID NO: 21, SEQ ID NO: 22, SEQ ID NO: 23, SEQ ID NO: 24, SEQ ID NO: 25, SEQ ID NO: 26 or a heavy chain variable region (HCVR) having a CDR3 domain comprising an amino acid sequence selected from the group consisting of SEQ ID NO: 4, SEQ ID NO: 27, SEQ ID NO: 28, SEQ ID NO: 29, SEQ ID NO: 30, SEQ ID NO: 31, SEQ ID NO: 32, SEQ ID NO: 33 and SEQ ID NO: 34.
- the antibody which bind human TNF ⁇ and comprises
- the invention also provides an aqueous pharmaceutical composition
- a polyol comprising a polyol, a surfactant, and a buffer system comprising citrate and/or phosphate with a pH of about 4 to 8, in amounts sufficient to formulate an antibody for therapeutic use at a concentration of greater than about 45 mg/ml.
- the polyol is mannitol and the surfactant is polysorbate 80.
- the composition includes 5-20 mg/ml of mannitol and 0.1-10 mg/ml of polysorbate 80.
- the composition includes the antibody D2E7.
- the invention also provides a liquid aqueous pharmaceutical formulation consisting of 1-150 mg/ml of antibody, 5-20 mg/ml of mannitol, 0.1-10 mg/ml of Tween-80, and a buffer system comprising citrate and/or phosphate, with a pH of 4 to 8.
- the antibody is directed to hTNF ⁇ .
- the formulation contains about 40 mg of antibody.
- the invention further provides a liquid aqueous pharmaceutical formulation comprising about 50 mg/ml of antibody, about 12 mg/ml of mannitol, about 1 mg/ml of Tween-80, and a buffer system comprising citrate and/or phosphate, with a pH of about 4 to about 8.
- the pH of the formulation is between about 4.5 to about 6.0.
- the pH is between about 4.8 to about 5.5.
- the pH of the invention is between about 5.0 to about 5.2.
- the liquid aqueous pharmaceutical formulation also includes about 1.305 mg/ml of citric acid, about 0.305 mg/ml of sodium citrate, about 1.53 mg/ml of disodium phosphate dihydrate, about 0.86 mg/ml of sodium dihydrogen phosphate dihydrate, and about 6.165 mg/ml of sodium chloride.
- the formulation of the invention includes an antibody which is directed to hTNF ⁇ .
- the formulation of the invention includes the antibody D2E7.
- the formulation of the invention is administered to a subject suffering from a disorder in which TNF ⁇ activity is detrimental such that TNF ⁇ activity in the subject is inhibited
- This invention pertains to a liquid aqueous pharmaceutical formulation with a pH of about 4 to about 8 which contains a high protein concentration, including an antibody concentration ranging from about 1 to about 150 mg/ml, and has enhanced stability.
- This invention also pertains to a liquid aqueous pharmaceutical formulation for therapeutic use in a subject suffering from a condition characterized by detrimental TNF ⁇ activity.
- the formulation of the invention comprises the following constituents: an antibody which binds to human TNF ⁇ with high affinity, a low off rate and high neutralizing capacity; a buffer, which includes citric acid, sodium citrate, disodium phosphate dihydrate, and sodium dihydrogen phosphate dihydrate; tonicity agents, which include mannitol and sodium chloride; a detergent, including polysorbate 80; and sodium hydroxide, for pH adjustment.
- subject is intended to include living organisms, e.g., prokaryotes and eukaryotes.
- subjects include mammals, e.g., humans, dogs, cows, horses, pigs, sheep, goats, cats, mice, rabbits, rats, and transgenic non-human animals.
- the subject is a human.
- pharmaceutical formulation refers to preparations which are in such form as to permit the biological activity of the active ingredients to be unequivocally effective, and which contain no additional components which are significantly toxic to the subjects to which the formulation would be administered.
- “Pharmaceutically acceptable” excipients are those which can reasonably be administered to a subject mammal to provide an effective dose of the active ingredient employed.
- a “stable” formulation is one in which the antibody therein essentially retains its physical stability and/or chemical stability and/or biological activity upon storage.
- Various analytical techniques for measuring protein stability are available in the art and are reviewed in Peptide and Protein Drug Delivery, 247-301, Vincent Lee Ed., Marcel Dekker, Inc., New York, N.Y., Pubs. (1991) and Jones, A. Adv. Drug Delivery Rev. 10: 35 29-90 (1993), for example.
- Stability can be measured at a selected temperature for a selected time period.
- the formulation is stable at room temperature (about 30° C.) or at 40° C. for at least 1 month and/or stable at about 2-8° C. for at least 1 year for at least 2 years.
- the formulation is preferably stable following freezing (to, e.g., ⁇ 70° C.) and thawing of the formulation, hereinafter referred to as a “freeze/thaw cycle.”
- An antibody “retains its physical stability” in a pharmaceutical formulation if it shows substantially no signs of aggregation, precipitation and/or denaturation upon visual examination of color and/or clarity, or as measured by UV light scattering or by size exclusion chromatography.
- An antibody “retains its chemical stability” in a pharmaceutical formulation if the chemical stability at a given time is such that the antibody is considered to still retain its biological activity as defined below.
- Chemical stability can be assessed by detecting and quantifying chemically altered forms of the antibody.
- Chemical alteration may involve size modification (e.g. clipping) which can be evaluated using size exclusion chromatography, SDS-PAGE and/or matrix-assisted laser desorption ionization/time-of-flight mass spectrometry (MALDI/TOF MS), for example.
- Other types of chemical alteration include charge alteration (e.g. occurring as a result of deamidation) which can be evaluated by ion-exchange chromatography, for example.
- An antibody “retains its biological activity” in a pharmaceutical formulation, if the antibody in a pharmaceutical formulation is biologically active for its intended purpose. For example, biological activity is retained if the biological activity of the antibody in the pharmaceutical formulation is within about 30%, about 20%, or about 10% (within the errors of the assay) of the biological activity exhibited at the time the pharmaceutical formulation was prepared (e.g., as determined in an antigen binding assay).
- Isotonic is a term recognized in the art. Isotonic can mean, for example, that the formulation of interest has essentially the same osmotic pressure as human blood. Isotonic formulations will generally have an osmotic pressure from about 250 to 350 mOsm. Isotonicity can be measured using a vapor pressure or ice-freezing type osmometer, for example. A “tonicity agent” is a compound which renders the formulation isotonic.
- a “polyol” is a substance with multiple hydroxyl groups, and includes sugars (reducing and nonreducing sugars), sugar alcohols and sugar acids. Preferred polyols herein have a molecular weight which is less than about 600 kD (e.g. in the range from about 120 to about 400 kD).
- a “reducing sugar” is one which contains a hemiacetal group that can reduce metal ions or react covalently with lysine and other amino groups in proteins and a “nonreducing sugar” is one which does not have these properties of a reducing sugar.
- reducing sugars are fructose, mannose, maltose, lactose, arabinose, xylose, ribose, rhamnose, galactose and glucose.
- Nonreducing sugars include sucrose, trehalose, sorbose, melezitose and raffinose.
- Mannitol, xylitol, erythritol, threitol, sorbitol and glycerol are examples of sugar alcohols.
- sugar acids these include L-gluconate and metallic salts thereof.
- the polyol is preferably one which does not crystallize at freezing temperatures (e.g.
- one ingredient of the formulation is mannitol in a concentration of 5 to 20 mg/ml. In a preferred embodiment of the invention, the concentration of mannitol is 7.5 to 15 mg/ml. In a more preferred embodiment of the invention, the concentration of mannitol is 10-14 mg/ml.
- buffer refers to a buffered solution that resists changes in pH by the action of its acid-base conjugate components.
- the buffer of this invention has a pH in the range from about 4 to about 8; preferably from about 4.5 to about 7; and most preferably has a pH in the range from about 5.0 to about 6.5.
- buffers that will control the pH in this range include acetate (e.g. sodium acetate), succinate (such as sodium succinate), gluconate, histidine, citrate and other organic acid buffers.
- a “therapeutically effective amount” or “effective amount” of an antibody refers to an amount effective in the prevention or treatment of a disorder for the treatment of which the antibody is effective.
- a “disorder” is any condition that would benefit from treatment with the antibody. This includes chronic and acute disorders or diseases including those pathological conditions which predisposes the subject to the disorder in question.
- a “preservative” is a compound which can be included in the formulation to essentially reduce bacterial action therein, thus facilitating the production of a multi-use formulation, for example.
- potential preservatives include octadecyldimethylbenzyl ammonium chloride, hexamethonium chloride, benzalkonium chloride (a mixture of alkylbenzyldimethylammonium chlorides in which the alkyl groups are long-chain compounds), and benzethonium chloride.
- preservatives include aromatic alcohols such as phenol, butyl and benzyl alcohol, alkyl parabens such as methyl or propyl paraben, catechol, resorcinol, cyclohexanol, 3-pentanol, and m-cresol.
- Treatment refers to both therapeutic treatment and prophylactic or preventative measures. Those in need of treatment include those already with the disorder as well as those in which the disorder is to be prevented.
- parenteral administration and “administered parenterally” as used herein means modes of administration other than enteral and topical administration, usually by injection, and includes, without limitation, intravenous, intramuscular, intraarterial, intrathecal, intracapsular, intraorbital, intracardiac, intradermal, intraperitoneal, transtracheal, subcutaneous, subcuticular, intraarticular, subcapsular, subarachnoid, intraspinal and intrasternal injection and infusion.
- systemic administration means the administration of a compound, drug or other material other than directly into the central nervous system, such that it enters the patient's system and, thus, is subject to metabolism and other like processes, for example, subcutaneous administration.
- phrases “pharmaceutically acceptable carrier” is art recognized and includes a pharmaceutically acceptable material, composition or vehicle, suitable for administration to mammals.
- the carriers include liquid or solid filler, diluent, excipient, solvent or encapsulating material, involved in carrying or transporting the subject agent from one organ, or portion of the body, to another organ, or portion of the body.
- Each carrier must be “acceptable” in the sense of being compatible with the other ingredients of the formulation and not injurious to the patient.
- hTNF ⁇ human TNF ⁇
- hTNF ⁇ human cytokine that exists as a 17 kD secreted form and a 26 kD membrane associated form, the biologically active form of which is composed of a trimer of noncovalently bound 17 kD molecules.
- the structure of hTNF ⁇ is described further in, for example, Pennica, D., et al. (1984) Nature 312:724-729; Davis, J. M., et al. (1987) Biochemistry 26:1322-1326; and Jones, E. Y., et al. (1989) Nature 338:225-228.
- human TNF ⁇ is intended to include recombinant human TNF ⁇ (rhTNF ⁇ ), which can be prepared by standard recombinant expression methods or purchased commercially (R & D Systems, Catalog No. 210-TA, Minneapolis, Minn.).
- antibody is intended to refer to immunoglobulin molecules comprised of four polypeptide chains, two heavy (H) chains and two light (L) chains inter-connected by disulfide bonds.
- Each heavy chain is comprised of a heavy chain variable region (abbreviated herein as HCVR or VH) and a heavy chain constant region.
- the heavy chain constant region is comprised of three domains, CH1, CH2 and CH3.
- Each light chain is comprised of a light chain variable region (abbreviated herein as LCVR or VL) and a light chain constant region.
- the light chain constant region is comprised of one domain, CL.
- VH and VL regions can be further subdivided into regions of hypervariability, termed complementarity determining regions (CDR), interspersed with regions that are more conserved, termed framework regions (FR).
- CDR complementarity determining regions
- FR framework regions
- Each VH and VL is composed of three CDRs and four FRs, arranged from amino-terminus to carboxy-terminus in the following order: FR1, CDR1, FR2, CDR2, FR3, CDR3, FR4.
- the formulation contains an antibody with CDR1, CDR2, and CDR3 sequences like those described in U.S. Pat. Nos. 6,090,382 and 6,258,562, each incorporated by reference herein.
- antigen-binding portion of an antibody refers to one or more fragments of an antibody that retain the ability to specifically bind to an antigen (e.g., hTNF ⁇ ). It has been shown that the antigen-binding function of an antibody can be performed by fragments of a full-length antibody.
- binding fragments encompassed within the term “antigen-binding portion” of an antibody include (i) a Fab fragment, a monovalent fragment consisting of the VL, VH, CL and CHI domains; (ii) a F(ab′) 2 fragment, a bivalent fragment comprising two Fab fragments linked by a disulfide bridge at the hinge region; (iii) a Fd fragment consisting of the VH and CH1 domains; (iv) a Fv fragment consisting of the VL and VH domains of a single arm of an antibody, (v) a dAb fragment (Ward et al., (1989) Nature 341:544-546 ), which consists of a VH domain; and (vi) an isolated complementarity determining region (CDR).
- a Fab fragment a monovalent fragment consisting of the VL, VH, CL and CHI domains
- a F(ab′) 2 fragment a bivalent fragment comprising two Fab fragments linked by
- the two domains of the Fv fragment, VL and VH are coded for by separate genes, they can be joined, using recombinant methods, by a synthetic linker that enables them to be made as a single protein chain in which the VL and VH regions pair to form monovalent molecules (known as single chain Fv (scFv); see e.g., Bird et al. (1988) Science 242:423-426; and Huston et al. (1988) Proc. Natl. Acad. Sci. USA 85:5879-5883).
- single chain Fv single chain Fv
- Such single chain antibodies are also intended to be encompassed within the term “antigen-binding portion” of an antibody.
- Other forms of single chain antibodies, such as diabodies are also encompassed.
- Diabodies are bivalent, bispecific antibodies in which VH and VL domains are expressed on a single polypeptide chain, but using a linker that is too short to allow for pairing between the two domains on the same chain, thereby forcing the domains to pair with complementary domains of another chain and creating two antigen binding sites (see e.g., Holliger, P., et al. (1993) Proc. Natl. Acad. Sci. USA 90:6444-6448; Poljak, R. J., et al. (1994) Structure 2:1121-1123).
- the formulation contains an antigen-binding portions described in U.S. Pat. Nos. 6,090,382 and 6,258,562, each incorporated by reference herein.
- an antibody or antigen-binding portion thereof may be part of a larger immunoadhesion molecules, formed by covalent or noncovalent association of the antibody or antibody portion with one or more other proteins or peptides.
- immunoadhesion molecules include use of the streptavidin core region to make a tetrameric scFv molecule (Kipriyanov, S. M., et al. (1995) Human Antibodies and Hybridomas 6:93- 101) and use of a cysteine residue, a marker peptide and a C-terminal polyhistidine tag to make bivalent and biotinylated scFv molecules (Kipriyanov, S. M., et al.
- Antibody portions such as Fab and F(ab′) 2 fragments, can be prepared from whole antibodies using conventional techniques, such as papain or pepsin digestion, respectively, of whole antibodies.
- antibodies, antibody portions and immunoadhesion molecules can be obtained using standard recombinant DNA techniques, as described herein.
- human antibody is intended to include antibodies having variable and constant regions derived from human germline immunoglobulin sequences.
- the human antibodies of the invention may include amino acid residues not encoded by human germline immunoglobulin sequences (e.g., mutations introduced by random or site-specific mutagenesis in vitro or by somatic mutation in vivo), for example in the CDRs and in particular CDR3.
- the term “human antibody”, as used herein, is not intended to include antibodies in which CDR sequences derived from the germline of another mammalian species, such as a mouse, have been grafted onto human framework sequences.
- recombinant human antibody is intended to include all human antibodies that are prepared, expressed, created or isolated by recombinant means, such as antibodies expressed using a recombinant expression vector transfected into a host cell (described further in Section II, below), antibodies isolated from a recombinant, combinatorial human antibody library (described further in Section III, below), antibodies isolated from an animal (e.g., a mouse) that is transgenic for human immunoglobulin genes (see e.g., Taylor, L. D., et al. (1992) Nucl. Acids Res.
- Such recombinant human antibodies have variable and constant regions derived from human germline immunoglobulin sequences. In certain embodiments, however, such recombinant human antibodies are subjected to in vitro mutagenesis (or, when an animal transgenic for human Ig sequences is used, in vivo somatic mutagenesis) and thus the amino acid sequences of the VH and VL regions of the recombinant antibodies are sequences that, while derived from and related to human germline VH and VL sequences, may not naturally exist within the human antibody germline repertoire in vivo.
- an “isolated antibody”, as used herein, is intended to refer to an antibody that is substantially free of other antibodies having different antigenic specificities (e.g., an isolated antibody that specifically binds hTNF ⁇ is substantially free of antibodies that specifically bind antigens other than hTNF ⁇ .
- An isolated antibody that specifically binds hTNF ⁇ may, however, have cross-reactivity to other antigens, such as TNF ⁇ molecules from other species.
- an isolated antibody may be substantially free of other cellular material and/or chemicals.
- a “neutralizing antibody”, as used herein is intended to refer to an antibody whose binding to hTNF ⁇ results in inhibition of the biological activity of hTNF ⁇ .
- This inhibition of the biological activity of hTNF ⁇ can be assessed by measuring one or more indicators of hTNF ⁇ biological activity, such as hTNF ⁇ -induced cytotoxicity (either in vitro or in vivo), hTNF ⁇ -induced cellular activation and hTNF ⁇ binding to hTNF ⁇ receptors.
- indicators of hTNF ⁇ biological activity can be assessed by one or more of several standard in vitro or in vivo assays known in the art, and described in U.S. Pat. Nos.
- the ability of an antibody to neutralize hTNF ⁇ activity is assessed by inhibition of hTNF ⁇ -induced cytotoxicity of L929 cells.
- the ability of an antibody to inhibit hTNF ⁇ -induced expression of ELAM-1 on HUVEC, as a measure of hTNF ⁇ -induced cellular activation can be assessed.
- surface plasmon resonance refers to an optical phenomenon that allows for the analysis of real-time biospecific interactions by detection of alterations in protein concentrations within a biosensor matrix, for example using the BIAcore system (Pharmacia Biosensor AB, Uppsala, Sweden and Piscataway, N.J.).
- BIAcore Pharmaacia Biosensor AB, Uppsala, Sweden and Piscataway, N.J.
- K off is intended to refer to the off rate constant for dissociation of an antibody from the antibody/antigen complex.
- K d is intended to refer to the dissociation constant of a particular antibody-antigen interaction.
- the invention is directed to a liquid aqueous pharmaceutical formulation comprising a therapeutically effective amount of an antibody in a buffered solution forming a formulation having a pH between about 4 and about 8 and having an extended shelf life, preferably of at least about 18 months.
- the liquid aqueous pharmaceutical formulation of the invention has enhanced stability.
- the formulation is not light sensitive.
- the claimed formulation remains stable following at least 3 freeze/thaw cycles.
- the pharmaceutical formulation of the invention is suitable for single use sc injection.
- Antibodies that can be used in the formulation include polyclonal, monoclonal, recombinant antibodies, single chain antibodies, hybrid antibodies, chimeric antibodies, humanized antibodies, or fragments thereof.
- Antibody-like molecules containing one or two binding sites for an antigen and a Fc-part of an immunoglobulin can also be used.
- An example of an antibody-like molecule is the active ingredient etanercept or infliximab.
- Preferred antibodies used in the formulation are human antibodies which are cloned from human cells or from gene-archives representing the human antibody-reservoir.
- Especially preferred among the human antibodies are antibodies directed against the antigen TNF ⁇ , including human TNF ⁇ (or hTNF ⁇ ).
- the formulation of the invention includes a combination of antibodies (two or more), or a “cocktail” of antibodies.
- the formulation can include the antibody D2E7 and one or more additional antibodies.
- the formulation contains an antibody, or antigen-binding portion thereof, dissociates from human TNF ⁇ with a K d of 1 ⁇ 10 ⁇ 8 M or less and a K off rate constant of 1 ⁇ 10 ⁇ 3 s ⁇ 1 or less, both determined by surface plasmon resonance, and neutralizes human TNF ⁇ cytotoxicity in a standard in vitro L929 assay with an IC 50 of 1 ⁇ 10 ⁇ 7 M or less.
- the formulation of the invention contains an antibody, or antigen-binding portion thereof, like those described in U.S. Pat. Nos. 6,090,382 and 6,258,562, each incorporated by reference herein.
- the formulation of the invention contains D2E7 antibodies and antibody portions, D2E7-related antibodies and antibody portions, and other human antibodies and antibody portions with equivalent properties to D2E7, such as high affinity binding to hTNF ⁇ with low dissociation kinetics and high neutralizing capacity.
- the formulation of the invention contains an isolated human antibody, or an antigen-binding portion thereof, that dissociates from human TNF ⁇ with a K d of 1 ⁇ 10 ⁇ 8 M or less and a K off rate constant of 1 ⁇ 10 ⁇ 3 s ⁇ 1 or less, both determined by surface plasmon resonance, and neutralizes human TNF ⁇ cytotoxicity in a standard in vitro L929 assay with an IC 50 of 1 ⁇ 10 ⁇ 7 M or less.
- the isolated human antibody, or antigen-binding portion thereof dissociates from human TNF ⁇ with a K off of 5 ⁇ 10 ⁇ 4 s ⁇ 1 or less, or even more preferably, with a K off of 1 ⁇ 10 ⁇ 4 s ⁇ 1 or less. More preferably, the isolated human antibody, or antigen-binding portion thereof, neutralizes human TNF ⁇ cytotoxicity in a standard in vitro L929 assay with an IC 50 of 1 ⁇ 10 ⁇ 8 M or less, even more preferably with an IC 50 of 1 ⁇ 10 ⁇ 9 M or less and still more preferably with an IC 50 of 5 ⁇ 10 ⁇ 10 M or less.
- the formulation contains an antibody which is an isolated human recombinant antibody, or an antigen-binding portion thereof.
- the formulation contains an antibody which also neutralizes TNF ⁇ -induced cellular activation, as assessed using a standard in vitro assay for TNF ⁇ -induced ELAM-1 expression on human umbilical vein endothelial cells (HUVEC).
- the present invention features formulations (e.g., protein formulations and/or antibody formulations) having improved properties as compared to art-recognized formulations.
- the formulations of the invention have an improved shelf life and/or stability as compared to art recognized formulations.
- the formulations of the invention comprise a high protein concentration, including, for example, a protein concentration greater than about 45 mg/ml, a protein concentration greater than about 50 mg/ml, a protein concentration greater than about 100 mg/ml, or a protein concentration greater than about 150 mg/ml.
- the protein is an antibody.
- the antibody is D2E7.
- the invention also provides an aqueous pharmaceutical composition
- a aqueous pharmaceutical composition comprising a polyol, a surfactant, and a buffer system comprising citrate and/or phosphate with a pH of about 4 to 8, in amounts sufficient to formulate an antibody for therapeutic use at a concentration of greater than about, for example, 45 mg/ml.
- the antibody of interest is performed according to standard methods known in the art.
- the antibody used in the formulation is expressed in CHO cells and purified by a standard series of chromatography steps.
- the antibody is directed to hTNF ⁇ , and is prepared according to the methods described in U.S. Pat. Nos. 6,090,382 and 6,258,562, each incorporated by reference herein.
- the pharmaceutical formulation comprising the antibody is prepared.
- the therapeutically effective amount of antibody present in the formulation is determined, for example, by taking into account the desired dose volumes and mode(s) of administration.
- the concentration of the antibody in the formulation is between about 1 to about 150 mg of antibody per ml of liquid formulation. In a preferred embodiment, the concentration of the antibody in the formulation is between about 5 to about 80 mg per ml. In another preferred embodiment, the concentration of the antibody in the formulation is between about 25 to about 50 mg/ml.
- the formulation is especially suitable for large antibody dosages of more than 15 mg/ml. In a preferred embodiment, the concentration of the antibody is 50 mg/ml.
- the concentration of the antibody in the formulation is about 1-150 mg/ml, about 5-145 mg/ml, about 10-140 mg/ml, about 15-135 mg/ml, about 20-130 mg/ml, about 25-125 mg/ml, about 30-120 mg/ml, about 35-115 mg/ml, about 40-110 mg/ml, about 45-105 mg/ml, about 50-100 mg/ml, about 55-95 mg/ml, about 60-90 mg/ml, about 65-85 mg/ml, about 70-80 mg/ml, or about 75 mg/ml.
- Ranges intermediate to the above recited concentrations are also intended to be part of this invention.
- ranges of values using a combination of any of the above recited values as upper and/or lower limits are intended to be included.
- the invention provides a formulation with an extended shelf life comprising of an active ingredient, preferably an antibody, in combination with mannitol, citric acid monohydrate, sodium citrate, disodium phosphate dihydrate, sodium dihydrogen phosphate dihydrate, sodium chloride, polysorbate 80, water, and sodium hydroxide.
- the formulation of the invention has an extended shelf life of at least about 18 months in the liquid state. Freezing the formulation of the invention can also be used to further extend its shelf life.
- An aqueous formulation is prepared comprising the antibody in a pH-buffered solution.
- the buffer of this invention has a pH ranging from about 4 to about 8, preferably from about 4.5 to about 6.0, more preferably from about 4.8 to about 5.5, and most preferably has a pH of about 5.0 to about 5.2. Ranges intermediate to the above recited pH's are also intended to be part of this invention. For example, ranges of values using a combination of any of the above recited values as upper and/or lower limits are intended to be included. Examples of buffers that will control the pH within this range include acetate (e.g. sodium acetate), succinate (such as sodium succinate), gluconate, histidine, citrate and other organic acid buffers.
- the formulation comprises a buffer system which contains citrate and phosphate to maintain the pH in a range of about 4 to about 8.
- the pH range is from about 4.5 to about 6.0, more preferably from about pH 4.8 to about 5.5, and most preferably in a pH range of about 5.0 to about 5.2.
- the buffer system includes citric acid monohydrate, sodium citrate, disodium phosphate dihydrate, and/or sodium dihydrogen phosphate dihydrate.
- the buffer system includes about 1.3 mg/ml of citric acid (e.g., 1.305 mg/ml), about 0.3 mg/ml of sodium citrate (e.g., 0.305 mg/ml), about 1.5 mg/ml of disodium phosphate dihydrate (e.g. 1.53 mg/ml), about 0.9 mg/ml of sodium dihydrogen phosphate dihydrate (e.g., 0.86), and about 6.2 mg/ml of sodium chloride (e.g., 6.165 mg/ml).
- citric acid e.g., 1.305 mg/ml
- sodium citrate e.g. 0.305 mg/ml
- 1.5 mg/ml of disodium phosphate dihydrate e.g. 1.53 mg/ml
- about 0.9 mg/ml of sodium dihydrogen phosphate dihydrate e.g. 0.86
- about 6.2 mg/ml of sodium chloride e.g., 6.165 mg/ml
- the buffer system includes 1-1.5 mg/ml of citric acid, 0.25 to 0.5 mg/ml of sodium citrate, 1.25 to 1.75 mg/ml of of disodium phosphate dihydrate, 0.7 to 1.1 mg/ml of sodium dihydrogen phosphate dihydrate, and 6.0 to 6.4 mg/ml of sodium chloride.
- the pH of the formulation is adjusted with sodium hydroxide.
- a polyol which acts as a tonicifier and may stabilize the antibody, is also included in the formulation.
- the polyol is added to the formulation in an amount which may vary with respect to the desired isotonicity of the formulation.
- the aqueous formulation is isotonic.
- the amount of polyol added may also alter with respect to the molecular weight of the polyol. For example, a lower amount of a monosaccharide (e.g. mannitol) may be added, compared to a disaccharide (such as trehalose).
- the polyol which is used in the formulation as a tonicity agent is mannitol.
- the mannitol concentration is about 5 to 20 mg/ml. In another preferred embodiment of the invention, the concentration of mannitol is about 7.5 to 15 mg/ml. In a more preferred embodiment of the formulation of the invention, the concentration of mannitol is about 10-14 mg/ml. In the most preferred embodiment, the concentration of mannitol is about 12 mg/ml. In another embodiment of the invention, the polyol sorbitol is included in the formulation.
- a detergent or surfactant is also added to the antibody formulation.
- exemplary detergents include nonionic detergents such as polysorbates (e.g. polysorbates 20, 80 etc) or poloxamers (e.g. poloxamer 188).
- the amount of detergent added is such that it reduces aggregation of the formulated antibody and/or minimizes the formation of particulates in the formulation and/or reduces adsorption.
- the formulation includes a surfactant which is a polysorbate.
- the formulation contains the detergent polysorbate 80 or Tween 80.
- Tween 80 is a term used to describe polyoxyethylene (20) sorbitanmonooleate (see Fiedler, Lexikon der Hifsstoffe, Editio Cantor Verlag Aulendorf, 4th edi., 1996).
- the formulation contains between about 0.1 and about 10 mg/ml of polysorbate 80, more preferably between about 0.5 and about 5 mg/ml. In another preferred embodiment, about 0.1% polysorbate 80 is found in the formulation of the invention.
- the formulation is a 0.8 mL solution in a vial containing the ingredients shown below in Table 1.
- TABLE 1 1 vial with 0.8 mL solution for injection 1) contains: Name of ingredient Quantity Function Active substance: Antibody (D2E7) 2) 40.0 mg Active substance Excipients: Mannitol 9.6 mg Tonicity agent Citric acid monohydrate 1.044 mg Buffer Citric acid Sodium citrate 0.244 mg Buffer Sodium citrate Disodium phosphate 1.224 mg Buffer dihydrate Dibasic sodium phosphate dihydrate Sodium dihydrogen 0.688 mg Buffer phosphate dihydrate Monobasic sodium phosphate dihydrate Sodium chloride 4.932 mg Tonicity agent Polysorbate 80 0.8 mg Detergent Water for injections 759.028-759.048 mg Solvent Water for injection Sodium hydroxide 3) 0.02-0.04 mg pH adjustment Total 817.6 mg
- the formulation contains the above-identified agents (i.e. antibody, buffer, polyol and detergent) and is essentially free of one or more preservatives, such as benzyl alcohol, phenol, m-cresol, chlorobutanol and benzethonium Cl.
- a preservative may be included in the formulation, particularly where the formulation is a multidose formulation.
- One or more other pharmaceutically acceptable carriers, excipients or stabilizers such as those described in Remington's Pharmaceutical Sciences 16th edition, Osol, A. Ed. (1980) may be included in the formulation provided that they do not significantly adversely affect the desired characteristics of the formulation.
- Acceptable carriers, excipients or stabilizers are nontoxic to recipients at the dosages and concentrations employed and include; additional buffering agents; co-solvents; antioxidants including ascorbic acid and methionine; chelating agents such as EDTA; metal complexes (e.g. Zn-protein complexes); biodegradable polymers such as polyesters; and/or salt-forming counterions such as sodium.
- the formulation herein may also be combined with one or more other therapeutic agents as necessary for the particular indication being treated, preferably those with complementary activities that do not adversely affect the antibody of the formulation.
- Such therapeutic agents are suitably present in combination in amounts that are effective for the purpose intended. Additional therapeutic agents which can be combined with the formulation of the invention are further described in U.S. Pat. Nos. 6,090,382 and 6,258,562, each of which is incorporated herein by reference.
- the formulations to be used for in vivo administration must be sterile. This is readily accomplished by filtration through sterile filtration membranes, prior to, or following, preparation of the formulation.
- the language “effective amount” of the formulation is that amount necessary or sufficient to inhibit TNF ⁇ activity, e.g., prevent the various morphological and somatic symptoms of a detrimental TNF ⁇ activity-associated state.
- the effective amount of the formulation is the amount necessary to achieve the desired result.
- an effective amount of the formulation is the amount sufficient to inhibit detrimental TNF ⁇ activity.
- an effective amount of the formulation is 0.8 mL of the formulation containing 40 mg of antibody, as described in table 1.
- the effective amount can vary depending on such factors as the size and weight of the subject, or the type of illness. For example, the choice of a TNF ⁇ activity-inhibiting formulation can affect what constitutes an “effective amount”.
- One of ordinary skill in the art would be able to study the aforementioned factors and make the determination regarding the effective amount of the TNF ⁇ activity inhibiting formulation without undue experimentation.
- the regimen of administration can affect what constitutes an effective amount.
- the TNF ⁇ activity-inhibiting formulation can be administered to the subject either prior to or after the onset of detrimental TNF ⁇ activity. Further, several divided dosages, as well as staggered dosages, can be administered daily or sequentially, or the dose can be continuously infused, or can be a bolus injection. Further, the dosages of the TNF ⁇ activity-inhibiting formulation can be proportionally increased or decreased as indicated by the exigencies of the therapeutic or prophylactic situation.
- treatment includes the diminishment or alleviation of at least one symptom associated or caused by the state, disorder or disease being treated.
- treatment can be diminishment of one or several symptoms of a disorder or complete eradication of a disorder.
- Actual dosage levels of the active ingredients (antibody) in the pharmaceutical formulation of this invention may be varied so as to obtain an amount of the active ingredient that is effective to achieve the desired therapeutic response for a particular patient, composition, and mode of administration, without being toxic to the patient.
- the selected dosage level will depend upon a variety of factors including the activity of the antibody found in the formulation, the route of administration, the time of administration, the rate of excretion of the particular compound being employed, the duration of the treatment, other drugs, compounds and/or materials used in combination with the particular compound employed, the age, sex, weight, condition, general health and prior medical history of the patient being treated, and like factors well known in the medical arts.
- a physician or veterinarian having ordinary skill in the art can readily determine and prescribe the effective amount of the pharmaceutical composition of the present invention required.
- the physician or veterinarian could start doses of the compounds of the invention employed in the pharmaceutical formulation at levels lower than that required in order to achieve the desired therapeutic effect and gradually increase the dosage until the desired effect is achieved.
- a suitable daily dose of a formulation of the invention will be that amount of the formulation that is the lowest dose effective to produce a therapeutic effect. Such an effective dose will generally depend upon the factors described above.
- An effective amount of the formulation of the present invention is an amount that inhibits TNF ⁇ activity in a subject suffering from a disorder in which TNF ⁇ activity is detrimental.
- the formulation provides an effective dose of 40 mg per injection of the active ingredient, the antibody.
- the formulation provides an effective dose which ranges from about 1 to 150 mg of antibody.
- the effective daily dose of the pharmaceutical formulation may be administered as two, three, four, five, six or more sub-doses administered separately at appropriate intervals throughout the day, optionally, in unit dosage forms.
- the dosage of the antibody in the formulation is between about 5 to about 80 mg. In another embodiment, the dosage of the antibody in the formulation is between about 25 to about 50 mg.
- the formulation is especially suitable for large antibody dosages of more than 15 mg.
- the formulation provides an antibody at a dose of about 40 mg.
- the antibody is directed to TNF ⁇ . In the most preferred embodiment, the antibody is D2E7.
- the dosage of the antibody in the formulation is between about 1-150 mg, about 5-145 mg, about 10-140 mg, about 15-135 mg, about 20-130 mg, about 25-125 mg, about 30-120 mg, about 35-115 mg, about 40-110 mg, about 45-105 mg, about 50-100 mg, about 55-95 mg, about 60-90 mg, about 65-85 mg, about 70-80 mg, or about 75 mg.
- the dosage of the antibody is 40 mg.
- the antibody is directed to TNF ⁇ .
- the antibody is D2E7. Ranges intermediate to the above recited dosages, e.g., about 2-149 mg, are also intended to be part of this invention. For example, ranges of values using a combination of any of the above recited values as upper and/or lower limits are intended to be included.
- dosage values may vary with the severity of the condition to be alleviated. It is to be further understood that for any particular subject, specific dosage regimens should be adjusted over time according to the individual need and the professional judgment of the person administering or supervising the administration of the compositions, and that dosage ranges set forth herein are exemplary only and are not intended to limit the scope or practice of the claimed composition.
- the invention provides a pharmaceutical formulation with an extended shelf life, which, in one embodiment, is used to inhibit TNF ⁇ activity in a subject suffering from a disorder in which TNF ⁇ activity is detrimental, comprising administering to the subject an antibody or antibody portion of the invention such that TNF ⁇ activity in the subject is inhibited.
- the TNF ⁇ is human TNF ⁇ and the subject is a human subject.
- the subject can be a mammal expressing a TNF ⁇ with which an antibody of the invention cross-reacts.
- the subject can be a mammal into which has been introduced hTNF ⁇ (e.g., by administration of hTNF ⁇ or by expression of an hTNF ⁇ transgene).
- a formulation of the invention can be administered to a human subject for therapeutic purposes (discussed further below).
- the liquid pharmaceutical formulation is easily administratable, which includes, for example, a formulation which is self-administered by the patient.
- the formulation of the invention is administered through sc injection, preferably single use.
- a formulation of the invention can be administered to a non-human mammal expressing a TNF ⁇ with which the antibody cross-reacts (e.g., a primate, pig or mouse) for veterinary purposes or as an animal model of human disease. Regarding the latter, such animal models may be useful for evaluating the therapeutic efficacy of antibodies of the invention (e.g., testing of dosages and time courses of administration).
- a disorder in which TNF ⁇ activity is detrimental is intended to include diseases and other disorders in which the presence of TNF ⁇ in a subject suffering from the disorder has been shown to be or is suspected of being either responsible for the pathophysiology of the disorder or a factor that contributes to a worsening of the disorder. Accordingly, a disorder in which TNF ⁇ activity is detrimental is a disorder in which inhibition of TNF ⁇ activity is expected to alleviate the symptoms and/or progression of the disorder. Such disorders may be evidenced, for example, by an increase in the concentration of TNF ⁇ in a biological fluid of a subject suffering from the disorder (e.g., an increase in the concentration of TNF ⁇ in serum, plasma, synovial fluid, etc. of the subject), which can be detected, for example, using an anti-TNF ⁇ antibody as described above.
- TNF ⁇ activity is detrimental.
- disorders in which TNF ⁇ activity is detrimental are described in U.S. application Ser. No. 60/397275, incorporated by reference herein.
- Examples in which TNF ⁇ activity is detrimental are also described in U.S. Pat. Nos. 6,015,557, 6,177,077, 6,379,666, 6,419,934, 6,419,944, 6,423,321, and 6,428,787; U.S. patent application Ser. Nos. US2001/0016195, US2001/0004456, and US2001/026801; WO 00/50079 and WO 01/49321, each incorporated by reference herein.
- Tumor necrosis factor has an established role in the pathophysiology of sepsis, with biological effects that include hypotension, myocardial suppression, vascular leakage syndrome, organ necrosis, stimulation of the release of toxic secondary mediators and activation of the clotting cascade (see e.g., Tracey, K. J. and Cerami, A. (1994) Annu. Rev. Med. 45:491-503; Russell, D and Thompson, R. C. (1993) Curr. Opin. Biotech. 4:714-721). Accordingly, the formulation of the invention can be used to treat sepsis in any of its clinical settings, including septic shock, endotoxic shock, gram negative sepsis and toxic shock syndrome.
- the formulation of the invention can be coadministered with one or more additional therapeutic agents that may further alleviate sepsis, such as an interleukin-1 inhibitor (such as those described in PCT Publication Nos. WO 92/16221 and WO 92/17583), the cytokine interleukin-6 (see e.g., PCT Publication No. WO 93/11793) or an antagonist of platelet activating factor (see e.g., European Patent Application Publication No. EP 374 510).
- an interleukin-1 inhibitor such as those described in PCT Publication Nos. WO 92/16221 and WO 92/17583
- the cytokine interleukin-6 see e.g., PCT Publication No. WO 93/11793
- an antagonist of platelet activating factor see e.g., European Patent Application Publication No. EP 374 510.
- the formulation of the invention is administered to a human subject within a subgroup of sepsis patients having a serum or plasma concentration of IL-6 above 500 pg/ml, and more preferably 1000 pg/ml, at the time of treatment (see PCT Publication No. WO 95/20978 by Daum, L., et al.).
- Tumor necrosis factor has been implicated in playing a role in the pathophysiology of a variety of autoimmune diseases.
- TNF ⁇ has been implicated in activating tissue inflammation and causing joint destruction in rheumatoid arthritis (see e.g., Tracey and Cerami, supra; Arend, W. P. and Dayer, J-M. (1995) Arth. Rheum. 38:151-160; Fava, R. A., et al. (1993) Clin. Exp. Immunol. 94:261-266).
- TNF ⁇ also has been implicated in promoting the death of islet cells and in mediating insulin resistance in diabetes (see e.g., Tracey and Cerami, supra; PCT Publication No.
- TNF ⁇ also has been implicated in mediating cytotoxicity to oligodendrocytes and induction of inflammatory plaques in multiple sclerosis (see e.g., Tracey and Cerami, supra).
- Chimeric and humanized murine anti-hTNF ⁇ antibodies have undergone clinical testing for treatment of rheumatoid arthritis (see e.g., Elliott, M. J., et al. (1994) Lancet 344:1125-1127; Elliot, M. J., et al. (1994) Lancet 344:1105-1110; Rankin, E. C., et al. (1995) Br. J. Rheumatol. 34:334-342).
- the formulation of the invention can be used to treat autoimmune diseases, in particular those associated with inflammation, including rheumatoid arthritis, rheumatoid spondylitis, osteoarthritis and gouty arthritis, allergy, multiple sclerosis, autoimmune diabetes, autoimmune uveitis and nephrotic syndrome.
- the formulation is administered systemically, although for certain disorders, local administration of the antibody or antibody portion at a site of inflammation may be beneficial (e.g., local administration in the joints in rheumatoid arthritis or topical application to diabetic ulcers, alone or in combination with a cyclohexane-ylidene derivative as described in PCT Publication No. WO 93/19751).
- Tumor necrosis factor has been implicated in mediating biological effects observed in a variety of infectious diseases.
- TNF ⁇ has been implicated in mediating brain inflammation and capillary thrombosis and infarction in malaria (see e.g., Tracey and Cerami, supra).
- TNF ⁇ also has been implicated in mediating brain inflammation, inducing breakdown of the blood-brain barrier, triggering septic shock syndrome and activating venous infarction in meningitis (see e.g., Tracey and Cerami, supra).
- TNF ⁇ also has been implicated in inducing cachexia, stimulating viral proliferation and mediating central nervous system injury in acquired immune deficiency syndrome (AIDS) (see e.g., Tracey and Cerami, supra).
- AIDS acquired immune deficiency syndrome
- the antibodies, and antibody portions, of the invention can be used in the treatment of infectious diseases, including bacterial meningitis (see e.g., European Patent Application Publication No. EP 585 705), cerebral malaria, AIDS and AIDS-related complex (ARC) (see e.g., European Patent Application Publication No. EP 230 574), as well as cytomegalovirus infection secondary to transplantation (see e.g., Fietze, E., et al. (1994) Transplantation 58:675-680).
- infectious diseases including bacterial meningitis (see e.g., European Patent Application Publication No. EP 585 705), cerebral malaria, AIDS and AIDS-related complex (ARC) (see e.g., European Patent Application Publication No. EP 230 574), as well as cytomegalovirus infection secondary to transplantation (see e.g., Fietze, E., et al. (1994) Transplantation 58:675-680).
- the formulation of the invention also
- Tumor necrosis factor has been implicated as a key mediator of allograft rejection and graft versus host disease (GVHD) and in mediating an adverse reaction that has been observed when the rat antibody OKT3, directed against the T cell receptor CD3 complex, is used to inhibit rejection of renal transplants (see e.g., Tracey and Cerami, supra; Eason, J. D., et al. (1995) Transplantation 59:300-305; Suthanthiran, M. and Strom, T. B. (1994) New Engl. J. Med. 331:365-375). Accordingly, the formulation of the invention, can be used to inhibit transplant rejection, including rejections of allografts and xenografts and to inhibit GVHD.
- GVHD graft versus host disease
- the antibody or antibody portion may be used alone, more preferably it is used in combination with one or more other agents that inhibit the immune response against the allograft or inhibit GVHD.
- the formulation of the invention is used in combination with OKT3 to inhibit OKT3-induced reactions.
- the formulation of the invention is used in combination with one or more antibodies directed at other targets involved in regulating immune responses, such as the cell surface molecules CD25 (interleukin-2 receptor- ⁇ ), CD11a (LFA-1), CD54 (ICAM-1), CD4, CD45, CD28/CTLA4, CD80 (B7-1) and/or CD86 (B7-2).
- the formulation of the invention is used in combination with one or more general immunosuppressive agents, such as cyclosporin A or FK506.
- Tumor necrosis factor has been implicated in inducing cachexia, stimulating tumor growth, enhancing metastatic potential and mediating cytotoxicity in malignancies (see e.g., Tracey and Cerami, supra).
- the formulation of the invention can be used in the treatment of malignancies, to inhibit tumor growth or metastasis and/or to alleviate cachexia secondary to malignancy.
- the formulation may be administered systemically or locally to the tumor site.
- Tumor necrosis factor has been implicated in the pathophysiology of adult respiratory distress syndrome, including stimulating leukocyte-endothelial activation, directing cytotoxicity to pneumocytes and inducing vascular leakage syndrome (see e.g., Tracey and Cerami, supra).
- the formulation of the invention can be used to treat various pulmonary disorders, including adult respiratory distress syndrome (see e.g., PCT Publication No. WO 91/04054), shock lung, chronic pulmonary inflammatory disease, pulmonary sarcoidosis, pulmonary fibrosis and silicosis.
- the formulation may be administered systemically or locally to the lung surface, for example as an aerosol.
- Tumor necrosis factor has been implicated in the pathophysiology of inflammatory bowel disorders (see e.g., Tracy, K. J., et al. (1986) Science 234:470-474; Sun, X-M., et al. (1988) J. Clin. Invest. 81:1328-1331; MacDonald, T. T., et al. (1990) Clin. Exp. Immunol. 81:301-305).
- Chimeric murine anti-hTNF ⁇ antibodies have undergone clinical testing for treatment of Crohn's disease (van Dullemen, H. M., et al. (1995) Gastroenterology 109:129-135).
- the formulation of the invention also can be used to treat intestinal disorders, such as idiopathic inflammatory bowel disease, which includes two syndromes, Crohn's disease and ulcerative colitis.
- the formulation of the invention also can be used to treat various cardiac disorders, including ischemia of the heart (see e.g., European Patent Application Publication No. EP 453 898) and heart insufficiency (weakness of the heart muscle) (see e.g., PCT Publication No. WO 94/20139).
- ischemia of the heart see e.g., European Patent Application Publication No. EP 453 898
- heart insufficiency weakness of the heart muscle
- the pharmaceutical formulation of the invention also can be used to treat various other disorders in which TNF ⁇ activity is detrimental.
- diseases and disorders in which TNF ⁇ activity has been implicated in the pathophysiology include inflammatory bone disorders and bone resorption disease (see e.g., Bertolini, D. R., et al. (1986) Nature 319:516-518; Konig, A., et al. (1988) J. Bone Miner. Res. 3:621-627; Lerner, U. H. and Ohlin, A. (1993) J. Bone Miner. Res. 8:147-155; and Shankar, G. and Stern, P. H.
- hepatitis including alcoholic hepatitis (see e.g., McClain, C. J. and Cohen, D. A. (1989) Hepatology 9:349-35 1; Felver, M. E., et al. (1990) Alcohol. Clin. Exp. Res. 14:255-259; and Hansen, J., et al. (1994) Hepatology 20:461-474) and viral hepatitis (Sheron, N., et al. (1991) J. Hepatol. 12:241-245; and Hussain, M. J., et al. (1994) J. Clin. Pathol.
- TNF ⁇ activity is detrimental
- disorders in which TNF ⁇ activity is detrimental include, but are not limited to, adult Still's disease, Alzheimer's disease, ankylosing spondylitis, asthma, cancer and cachexia, atherosclerosis, chronic atherosclerosis, chronic fatigue syndrome, liver failure, chronic liver failure, obstructive pulmonary disease, chronic obstructive pulmonary disease, congestive heart failure, dermatopolymyositis, diabetic macrovasculopathy, endometriosis, familial periodic fevers, fibrosis, hemodialysis, Jarisch-Herxheimer reaction, juvenile RA, Kawasaki syndrome, myelo dysplastic syndrome, myocardial infarction, panciaticular vulgaris, periodontal disease, peripheral neuropathy, polyarticular, polymyositis, progressive renal failure, psoriasis, psoriatic arthritis, Reiter's syndrome, sarcoidosis, scleroderma, spondyloarthropathies, Still
- Materials which were used in the formulation include: mannitol, citric acid monohydrate (citric acid), sodium citrate, disodium phosphate dihydrate (dibasic sodium phosphate dihydrate), sodium dihydrogen phosphate dihydrate (monobasic sodium phosphate dihydrate), sodium chloride, polysorbate 80, water for the injections, sodium hydroxide, which was used as a 1M solution to adjust the pH, and protein concentrate (e.g., antibody concentrate).
- a sodium hydroxide solution was prepared by combining 40.0 g of sodium hydroxide with 1000.8 g of water for injections.
- a buffer was prepared by dissolving the following pre-weighed ingredients (described above) in about 90% of the water for injections: mannitol, citric acid monohydrate, sodium citrate, disodium phosphate dihydrate, sodium dihydrogen phosphate, sodium chloride, and polysorbate 80. It was determined that the sequence of the addition of the buffer constituents was not important and can, therefore, be chosen at will.
- the pH of the solution was adjusted with 1M sodium hydroxide which was prepared as described above. After the addition of the sodium hydroxide, the final weight of the water was added.
- the buffer solution was then filtered through a sterilized filter (hydrophilic polyvinylidene difluoride, 0.22 ⁇ m pore size) into a sterilized receptacle.
- the filtration medium used was filtration sterilized nitrogen.
- the filtered buffer solution was then added to the thawed and pooled antibody concentrate (the active ingredient of the pharmaceutical formulation), prepared as follows.
- the antibody (concentrate) was thawed in a water bath prior to the preparation of the pharmaceutical formulation.
- 34.207 g of antibody concentrate was used, which is equivalent to 2.0 kg of protein with 60 mg protein/mL protein concentrate.
- the density of the concentrate was 1.0262 g/mL.
- the buffer was added while stirring, until the final weight of the bulk solution was reached.
- the formulation was then sterilized by filtration as described above, except the formulation was filtered through two sterile 0.22 ⁇ m membrane filters. Following sterilization, the formulation was packaged for use in either a vial or a pre-filled syringe.
- weight quantities and/or weight-to-volume ratios recited herein can be converted to moles and/or molarities using the art-recognized molecular weights of the recited ingredients.
- Weight quantities exemplified herein e.g., g or kg
- volumes e.g., of buffer or pharmaceutical formulation
- weight quantities can be proportionally adjusted when different formulation volumes are desired. For example, 32L, 20L, 10L, 5L, or 1L formulations would include 80%, 50%, 25%, 12.5%, or 2.5%, respectively, of the exemplified weight quantities.
- the drug substance was formulated in the same matrix as the finished product.
- Table 2 shows that the D2E7 antibody drug substance can be thawed/frozen at least 3 times without any detrimental effect on either chemical (cation exchange HPLC, size exclusion HPLC, colour, pH), physicochemical properties (subvisible particles, clarity) or biological activity (in vitro TNF neutralization assay). Also table 2 shows that the inclusion of polysorbate 80 improved the physicochemical properties of the D2E7 antibody drug substance as evidenced by the lower number of subvisible particles regardless whether a slow or fast freeze/thaw cycle was being used (see shaded areas in table 2).
- Tests were performed to determine if the formulation can support microbial growth. The results from these experiments showed that the formulation does not support microbial growth if stored at 20 to 25° C. for 14 days. This result was determined by directly inoculating the sterile formulation with microorganisms (e.g., Staphylococous aureus , ATCC-No.: 6538P, Candida albicans , ATCC-No.: 10231 , Aspergillus niger , ATCCC-No.: 16404 , Pseudomonas aeruginosa , ATCC-No.: 9027, an environmental isolate) at low level (NMT 100 cfu/mL).
- microorganisms e.g., Staphylococous aureus , ATCC-No.: 6538P, Candida albicans , ATCC-No.: 10231 , Aspergillus niger , ATCCC-No.: 16404 , P
- Inoculated formulations were then examined for overall microbial growth, e.g., for changes in turbidity. A lack of turbidity was an indication of no overall growth, and was detected in the inoculated containers after 14 days. Further, no organisms could be reisolated from these containers. Thus it was concluded that the formulation does not support microbial growth under these conditions.
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Public Health (AREA)
- Engineering & Computer Science (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Organic Chemistry (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Epidemiology (AREA)
- Immunology (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- Molecular Biology (AREA)
- Biochemistry (AREA)
- Physical Education & Sports Medicine (AREA)
- Diabetes (AREA)
- Mycology (AREA)
- Microbiology (AREA)
- Dermatology (AREA)
- Communicable Diseases (AREA)
- Cardiology (AREA)
- Rheumatology (AREA)
- Pulmonology (AREA)
- Oncology (AREA)
- Endocrinology (AREA)
- Heart & Thoracic Surgery (AREA)
- Hematology (AREA)
- Biomedical Technology (AREA)
- Tropical Medicine & Parasitology (AREA)
- Virology (AREA)
- Pain & Pain Management (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Biophysics (AREA)
- Genetics & Genomics (AREA)
Priority Applications (86)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US10/222,140 US20040033228A1 (en) | 2002-08-16 | 2002-08-16 | Formulation of human antibodies for treating TNF-alpha associated disorders |
MYPI2012001176A MY163027A (en) | 2002-08-16 | 2003-08-08 | FORMULATION OF HUMAN ANTIBODIES FOR TREATING TNF-(α) ASSOCIATED DISORDERS |
MYPI20033010A MY153718A (en) | 2002-08-16 | 2003-08-08 | Formulation of human antibodies for treating tnf-(?) associated disorders |
MYPI20070749A MY162068A (en) | 2002-08-16 | 2003-08-08 | Formulation of human antibodies for treating tnf-(alpha) associated disorders |
TW092122123A TWI331532B (en) | 2002-08-16 | 2003-08-12 | Formulation of human antibodies for treating tnf-alpha associated disorders |
EP03748439A EP1528933B1 (en) | 2002-08-16 | 2003-08-15 | Pharmaceutical anti-tnf-alpha antibody formulation |
CA2494756A CA2494756C (en) | 2002-08-16 | 2003-08-15 | Anti-tnf-alpha antibodies in solution and uses thereof |
ES10182610.5T ES2636692T3 (es) | 2002-08-16 | 2003-08-15 | Formulación de anticuerpos humanos para tratar trastornos asociados con TNF-alfa |
AR20030102982A AR040881A1 (es) | 2002-08-16 | 2003-08-15 | Formulacion de anticuerpos humanos para el tratamiento de trastornos asociados con tnf-alfa |
EP10182598A EP2363144A1 (en) | 2002-08-16 | 2003-08-15 | Pharmaceutical anti-TNF-alpha antibody formulation |
KR1020127026957A KR101367743B1 (ko) | 2002-08-16 | 2003-08-15 | 약제학적 항-종양 괴사 인자-α 항체 제제 |
CA2854798A CA2854798A1 (en) | 2002-08-16 | 2003-08-15 | Anti-tnf-alpha antibodies in solution and uses thereof |
EP10182610.5A EP2359856B1 (en) | 2002-08-16 | 2003-08-15 | Formulation of human antibodies for treating TNF-alpha associated disorders |
CN038242729A CN1688339B (zh) | 2002-08-16 | 2003-08-15 | 用于治疗TNF-α相关病症的人抗体的制剂 |
ES03748439T ES2387616T3 (es) | 2002-08-16 | 2003-08-15 | Formulación farmacéutica de anticuerpos anti-TNF-alfa |
CA2872091A CA2872091A1 (en) | 2002-08-16 | 2003-08-15 | Anti-tnf-alpha antibodies in solution and uses thereof |
EP20100182619 EP2361637A1 (en) | 2002-08-16 | 2003-08-15 | Formulation of human antibodies for treating TNF-alpha associated disorders |
KR1020057002604A KR20050067140A (ko) | 2002-08-16 | 2003-08-15 | 약제학적 항-종양 괴사 인자-α 항체 제제 |
AU2003267744A AU2003267744C1 (en) | 2002-08-16 | 2003-08-15 | Pharmaceutical anti-TNF-alpha antibody formulation |
PL406852A PL218834B1 (pl) | 2002-08-16 | 2003-08-15 | Preparat zawierający ludzkie przeciwciała do leczenia zaburzeń związanych z TNF-α |
PT03748439T PT1528933E (pt) | 2002-08-16 | 2003-08-15 | Formulação farmacêutica de anticorpos anti-tnf-alfa |
CA2882905A CA2882905C (en) | 2002-08-16 | 2003-08-15 | Anti-tnf-alpha antibodies in solution and uses thereof |
EP10182625A EP2363145A1 (en) | 2002-08-16 | 2003-08-15 | Pharmaceutical anti-TNF-alpha antibody formulation |
JP2004528780A JP4925582B2 (ja) | 2002-08-16 | 2003-08-15 | Tnf−アルファ関連疾患の治療用ヒト抗体の製剤 |
CN201010613946.7A CN102049045B (zh) | 2002-08-16 | 2003-08-15 | 用于治疗TNF-α相关病症的人抗体的制剂 |
NZ538030A NZ538030A (en) | 2002-08-16 | 2003-08-15 | Formulation of human antibodies for treating TNF-alpha associated disorders |
CA2882931A CA2882931C (en) | 2002-08-16 | 2003-08-15 | Anti-tnf-alpha antibodies in solution and uses thereof |
KR1020117007142A KR101273568B1 (ko) | 2002-08-16 | 2003-08-15 | 약제학적 항-종양 괴사 인자-α 항체 제제 |
PT101826105T PT2359856T (pt) | 2002-08-16 | 2003-08-15 | Formulação de anticorpos humanos para o tratamento de perturbações associadas ao tnf-alfa |
CN201010613919.XA CN102078608B (zh) | 2002-08-16 | 2003-08-15 | 用于治疗TNF-α相关病症的人抗体的制剂 |
SI200332534T SI2359856T1 (sl) | 2002-08-16 | 2003-08-15 | Formulacija humanih protiteles za zdravljenje motenj, povezanih s TNF-alfa |
MXPA05001841A MXPA05001841A (es) | 2002-08-16 | 2003-08-15 | Formulacion de anticuerpos humanos para tratar trastornos asociados con tnfa. |
BR0313492-0A BR0313492A (pt) | 2002-08-16 | 2003-08-15 | Formulação de anticorpos humanos para tratar distúrbios associados ao tnf-alfa |
SI200332176T SI1528933T1 (sl) | 2002-08-16 | 2003-08-15 | Farmacevtska formulacija protitelesa proti TNF-alfa |
DK10182610.5T DK2359856T3 (en) | 2002-08-16 | 2003-08-15 | Formulation of human antibodies for treating TNF-alpha associated disorders |
PCT/IB2003/004502 WO2004016286A2 (en) | 2002-08-16 | 2003-08-15 | Pharmaceutical anti-tnf-alpha antibody formulation |
CA2872088A CA2872088A1 (en) | 2002-08-16 | 2003-08-15 | Anti-tnf-alpha antibodies in solution and uses thereof |
DK03748439.1T DK1528933T3 (da) | 2002-08-16 | 2003-08-15 | Farmaceutisk anti-TNF-alpha-antistofformulering |
PL398596A PL218221B1 (pl) | 2002-08-16 | 2003-08-15 | Trwały ciekły wodny preparat farmaceutyczny zawierający ludzkie przeciwciała przeciw czynnikowi martwicy nowotworów alfa |
UY27940A UY27940A1 (es) | 2002-08-16 | 2003-08-15 | Formulacion de anticuerpos humanos para el tratamiento de trastornos asociados con tnf-a |
US10/525,292 US8216583B2 (en) | 2002-08-16 | 2003-08-15 | Formulation of human antibodies for treating TNF-α associated disorders |
PE2003000831A PE20040994A1 (es) | 2002-08-16 | 2003-08-15 | Formulacion de anticuerpos humanos referidos a transtornos asociados con tnf-alfa |
CA2882934A CA2882934C (en) | 2002-08-16 | 2003-08-15 | Anti-tnf-alpha antibodies in solution and uses thereof |
CA2872089A CA2872089C (en) | 2002-08-16 | 2003-08-15 | Anti-tnf-alpha antibodies in solution and uses thereof |
AT03748439T ATE555809T1 (de) | 2002-08-16 | 2003-08-15 | Pharmezeutische anti-tnf-alpha antikörper formulierung |
PL375272A PL212934B1 (pl) | 2002-08-16 | 2003-08-15 | Ciekly wodny preparat farmaceutyczny |
CN200910253163.XA CN101721702B (zh) | 2002-08-16 | 2003-08-15 | 用于治疗TNF-α相关疾病的人抗体的制剂 |
KR1020137022247A KR101529583B1 (ko) | 2002-08-16 | 2003-08-15 | 약제학적 항-종양 괴사 인자-α 항체 제제 |
CA2882907A CA2882907C (en) | 2002-08-16 | 2003-08-15 | Anti-tnf-alpha antibodies in solution and uses thereof |
ZA200501032A ZA200501032B (en) | 2002-08-16 | 2005-02-03 | Pharmaceutical anti-TNF-alpha antibody formulation. |
IL166809A IL166809A (en) | 2002-08-16 | 2005-02-10 | Aqueous liquid compositions contain human antibodies against a tnf |
HK05108068.5A HK1074008A1 (en) | 2002-08-16 | 2005-09-15 | Pharmaceutical anti-tnf-alpha antibody formulation |
CL2010000603A CL2010000603A1 (es) | 2002-08-16 | 2010-06-08 | Una formulacion farmaceutica acuosa liquida que comprende un anticuerpo contra htnf-alfa humano o una porcion de union al antigeno del mismo, un poliol; un tensioactivo; un sistema amortiguador de ph (div. sol. 1643-03). |
ARP100102557A AR077412A2 (es) | 2002-08-16 | 2010-07-14 | Formulacion farmaceutica composicon farmaceutica acuosa y formulacion farmaceutica acuosa liquida que comprende un anticuerpo |
IL207028A IL207028A (en) | 2002-08-16 | 2010-07-15 | Pharmaceutical composition for antibody tnf alpha antibody |
JP2011204759A JP5608619B2 (ja) | 2002-08-16 | 2011-09-20 | Tnf−アルファ関連疾患の治療用ヒト抗体の製剤 |
US13/471,820 US8932591B2 (en) | 2002-08-16 | 2012-05-15 | Formulation of human antibodies for treating TNF-α associated disorders |
CY20121100631T CY1113353T1 (el) | 2002-08-16 | 2012-07-17 | Φαρμακοτεχνικη μορφη αντι-τνf-αλφα αντισωματος |
JP2013235924A JP2014074034A (ja) | 2002-08-16 | 2013-11-14 | Tnf−アルファ関連疾患の治療用ヒト抗体の製剤 |
US14/091,661 US8802100B2 (en) | 2002-08-16 | 2013-11-27 | Formulation of human antibodies for treating TNF-alpha associated disorders |
US14/091,888 US8802101B2 (en) | 2002-08-16 | 2013-11-27 | Formulation of human antibodies for treating TNF-α associated disorders |
US14/091,938 US8795670B2 (en) | 2002-08-16 | 2013-11-27 | Formulation of human antibodies for treating TNF-alpha associated disorders |
US14/147,287 US8802102B2 (en) | 2002-08-16 | 2014-01-03 | Formulation of human antibodies for treating TNF-α associated disorders |
US14/322,581 US8911741B2 (en) | 2002-08-16 | 2014-07-02 | Formulation of human antibodies for treating TNF-alpha associated disorders |
US14/322,565 US8940305B2 (en) | 2002-08-16 | 2014-07-02 | Formulation of human antibodies for treating TNF-α associated disorders |
US14/453,461 US8916157B2 (en) | 2002-08-16 | 2014-08-06 | Formulation of human antibodies for treating TNF-α associated disorders |
US14/453,490 US8916158B2 (en) | 2002-08-16 | 2014-08-06 | Formulation of human antibodies for treating TNF-α associated disorders |
US14/558,182 US9114166B2 (en) | 2002-08-16 | 2014-12-02 | Formulation of human antibodies for treating TNF-α associated disorders |
JP2015099796A JP2015199741A (ja) | 2002-08-16 | 2015-05-15 | Tnf−アルファ関連疾患の治療用ヒト抗体の製剤 |
US14/799,211 US9220781B2 (en) | 2002-08-16 | 2015-07-14 | Formulation of human antibodies for treating TNF-alpha associated disorders |
US14/826,393 US9289497B2 (en) | 2002-08-16 | 2015-08-14 | Formulation of human antibodies for treating TNF-alpha associated disorders |
US14/826,383 US9272042B2 (en) | 2002-08-16 | 2015-08-14 | Formulation of human antibodies for treating TNF-alpha associated disorders |
US14/826,367 US9272041B2 (en) | 2002-08-16 | 2015-08-14 | Formulation of human antibodies for treating TNF-alpha associated disorders |
US14/826,357 US9327032B2 (en) | 2002-08-16 | 2015-08-14 | Formulation of human antibodies for treating TNF-alpha associated disorders |
US14/826,377 US9295725B2 (en) | 2002-08-16 | 2015-08-14 | Formulation of human antibodies for treating TNF-alpha associated disorders |
US14/884,279 US9302011B2 (en) | 2002-08-16 | 2015-10-15 | Formulation of human antibodies for treating TNF-α associated disorders |
US15/095,393 US9950066B2 (en) | 2002-08-16 | 2016-04-11 | Formulation of human antibodies for treating TNF-alpha associated disorders |
US15/418,465 US9732152B2 (en) | 2002-08-16 | 2017-01-27 | Formulation of human antibodies for treating TNF-alpha associated disorders |
US15/418,469 US9738714B2 (en) | 2002-08-16 | 2017-01-27 | Formulation of human antibodies for treating TNF-alpha associated disorders |
US15/418,460 US9750808B2 (en) | 2002-08-16 | 2017-01-27 | Formulation of human antibodies for treating TNF-alpha associated disorders |
JP2017074982A JP2017165736A (ja) | 2002-08-16 | 2017-04-05 | Tnf−アルファ関連疾患の治療用ヒト抗体の製剤 |
CY20171100527T CY1118991T1 (el) | 2002-08-16 | 2017-05-19 | Φαρμακοτεχνικη μορφη ανθρωπινων αντισωματων για θεραπεια σχετικων με tnf-αλφα διαταραχων |
US15/918,663 US20190054171A1 (en) | 2002-08-16 | 2018-03-12 | Formulation of human antibodies for treating tnf-alpha associated disorders |
US16/057,217 US20180339046A1 (en) | 2002-08-16 | 2018-08-07 | Formulation of human antibodies for treating tnf-alpha associated disorders |
US17/126,500 US20210113694A1 (en) | 2002-08-16 | 2020-12-18 | Formulation of human antibodies for treating tnf-alpha associated disorders |
US17/472,004 US20220241415A1 (en) | 2002-08-16 | 2021-09-10 | Formulation of human antibodies for treating tnf-alpha associated disorders |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US10/222,140 US20040033228A1 (en) | 2002-08-16 | 2002-08-16 | Formulation of human antibodies for treating TNF-alpha associated disorders |
Related Child Applications (2)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
US10/525,292 Continuation US8216583B2 (en) | 2002-08-16 | 2003-08-15 | Formulation of human antibodies for treating TNF-α associated disorders |
PCT/IB2003/004502 Continuation WO2004016286A2 (en) | 2002-08-16 | 2003-08-15 | Pharmaceutical anti-tnf-alpha antibody formulation |
Publications (1)
Publication Number | Publication Date |
---|---|
US20040033228A1 true US20040033228A1 (en) | 2004-02-19 |
Family
ID=31714885
Family Applications (27)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
US10/222,140 Abandoned US20040033228A1 (en) | 2002-08-16 | 2002-08-16 | Formulation of human antibodies for treating TNF-alpha associated disorders |
US10/525,292 Active 2026-10-08 US8216583B2 (en) | 2002-08-16 | 2003-08-15 | Formulation of human antibodies for treating TNF-α associated disorders |
US13/471,820 Expired - Lifetime US8932591B2 (en) | 2002-08-16 | 2012-05-15 | Formulation of human antibodies for treating TNF-α associated disorders |
US14/091,938 Expired - Lifetime US8795670B2 (en) | 2002-08-16 | 2013-11-27 | Formulation of human antibodies for treating TNF-alpha associated disorders |
US14/091,661 Expired - Lifetime US8802100B2 (en) | 2002-08-16 | 2013-11-27 | Formulation of human antibodies for treating TNF-alpha associated disorders |
US14/091,888 Expired - Lifetime US8802101B2 (en) | 2002-08-16 | 2013-11-27 | Formulation of human antibodies for treating TNF-α associated disorders |
US14/147,287 Expired - Lifetime US8802102B2 (en) | 2002-08-16 | 2014-01-03 | Formulation of human antibodies for treating TNF-α associated disorders |
US14/322,581 Expired - Lifetime US8911741B2 (en) | 2002-08-16 | 2014-07-02 | Formulation of human antibodies for treating TNF-alpha associated disorders |
US14/322,565 Expired - Lifetime US8940305B2 (en) | 2002-08-16 | 2014-07-02 | Formulation of human antibodies for treating TNF-α associated disorders |
US14/453,461 Expired - Lifetime US8916157B2 (en) | 2002-08-16 | 2014-08-06 | Formulation of human antibodies for treating TNF-α associated disorders |
US14/453,490 Expired - Lifetime US8916158B2 (en) | 2002-08-16 | 2014-08-06 | Formulation of human antibodies for treating TNF-α associated disorders |
US14/558,182 Expired - Lifetime US9114166B2 (en) | 2002-08-16 | 2014-12-02 | Formulation of human antibodies for treating TNF-α associated disorders |
US14/799,211 Expired - Lifetime US9220781B2 (en) | 2002-08-16 | 2015-07-14 | Formulation of human antibodies for treating TNF-alpha associated disorders |
US14/826,367 Expired - Fee Related US9272041B2 (en) | 2002-08-16 | 2015-08-14 | Formulation of human antibodies for treating TNF-alpha associated disorders |
US14/826,377 Expired - Fee Related US9295725B2 (en) | 2002-08-16 | 2015-08-14 | Formulation of human antibodies for treating TNF-alpha associated disorders |
US14/826,357 Expired - Fee Related US9327032B2 (en) | 2002-08-16 | 2015-08-14 | Formulation of human antibodies for treating TNF-alpha associated disorders |
US14/826,383 Expired - Fee Related US9272042B2 (en) | 2002-08-16 | 2015-08-14 | Formulation of human antibodies for treating TNF-alpha associated disorders |
US14/826,393 Expired - Fee Related US9289497B2 (en) | 2002-08-16 | 2015-08-14 | Formulation of human antibodies for treating TNF-alpha associated disorders |
US14/884,279 Expired - Fee Related US9302011B2 (en) | 2002-08-16 | 2015-10-15 | Formulation of human antibodies for treating TNF-α associated disorders |
US15/095,393 Expired - Lifetime US9950066B2 (en) | 2002-08-16 | 2016-04-11 | Formulation of human antibodies for treating TNF-alpha associated disorders |
US15/418,460 Expired - Lifetime US9750808B2 (en) | 2002-08-16 | 2017-01-27 | Formulation of human antibodies for treating TNF-alpha associated disorders |
US15/418,469 Expired - Lifetime US9738714B2 (en) | 2002-08-16 | 2017-01-27 | Formulation of human antibodies for treating TNF-alpha associated disorders |
US15/418,465 Expired - Lifetime US9732152B2 (en) | 2002-08-16 | 2017-01-27 | Formulation of human antibodies for treating TNF-alpha associated disorders |
US15/918,663 Abandoned US20190054171A1 (en) | 2002-08-16 | 2018-03-12 | Formulation of human antibodies for treating tnf-alpha associated disorders |
US16/057,217 Abandoned US20180339046A1 (en) | 2002-08-16 | 2018-08-07 | Formulation of human antibodies for treating tnf-alpha associated disorders |
US17/126,500 Abandoned US20210113694A1 (en) | 2002-08-16 | 2020-12-18 | Formulation of human antibodies for treating tnf-alpha associated disorders |
US17/472,004 Pending US20220241415A1 (en) | 2002-08-16 | 2021-09-10 | Formulation of human antibodies for treating tnf-alpha associated disorders |
Family Applications After (26)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
US10/525,292 Active 2026-10-08 US8216583B2 (en) | 2002-08-16 | 2003-08-15 | Formulation of human antibodies for treating TNF-α associated disorders |
US13/471,820 Expired - Lifetime US8932591B2 (en) | 2002-08-16 | 2012-05-15 | Formulation of human antibodies for treating TNF-α associated disorders |
US14/091,938 Expired - Lifetime US8795670B2 (en) | 2002-08-16 | 2013-11-27 | Formulation of human antibodies for treating TNF-alpha associated disorders |
US14/091,661 Expired - Lifetime US8802100B2 (en) | 2002-08-16 | 2013-11-27 | Formulation of human antibodies for treating TNF-alpha associated disorders |
US14/091,888 Expired - Lifetime US8802101B2 (en) | 2002-08-16 | 2013-11-27 | Formulation of human antibodies for treating TNF-α associated disorders |
US14/147,287 Expired - Lifetime US8802102B2 (en) | 2002-08-16 | 2014-01-03 | Formulation of human antibodies for treating TNF-α associated disorders |
US14/322,581 Expired - Lifetime US8911741B2 (en) | 2002-08-16 | 2014-07-02 | Formulation of human antibodies for treating TNF-alpha associated disorders |
US14/322,565 Expired - Lifetime US8940305B2 (en) | 2002-08-16 | 2014-07-02 | Formulation of human antibodies for treating TNF-α associated disorders |
US14/453,461 Expired - Lifetime US8916157B2 (en) | 2002-08-16 | 2014-08-06 | Formulation of human antibodies for treating TNF-α associated disorders |
US14/453,490 Expired - Lifetime US8916158B2 (en) | 2002-08-16 | 2014-08-06 | Formulation of human antibodies for treating TNF-α associated disorders |
US14/558,182 Expired - Lifetime US9114166B2 (en) | 2002-08-16 | 2014-12-02 | Formulation of human antibodies for treating TNF-α associated disorders |
US14/799,211 Expired - Lifetime US9220781B2 (en) | 2002-08-16 | 2015-07-14 | Formulation of human antibodies for treating TNF-alpha associated disorders |
US14/826,367 Expired - Fee Related US9272041B2 (en) | 2002-08-16 | 2015-08-14 | Formulation of human antibodies for treating TNF-alpha associated disorders |
US14/826,377 Expired - Fee Related US9295725B2 (en) | 2002-08-16 | 2015-08-14 | Formulation of human antibodies for treating TNF-alpha associated disorders |
US14/826,357 Expired - Fee Related US9327032B2 (en) | 2002-08-16 | 2015-08-14 | Formulation of human antibodies for treating TNF-alpha associated disorders |
US14/826,383 Expired - Fee Related US9272042B2 (en) | 2002-08-16 | 2015-08-14 | Formulation of human antibodies for treating TNF-alpha associated disorders |
US14/826,393 Expired - Fee Related US9289497B2 (en) | 2002-08-16 | 2015-08-14 | Formulation of human antibodies for treating TNF-alpha associated disorders |
US14/884,279 Expired - Fee Related US9302011B2 (en) | 2002-08-16 | 2015-10-15 | Formulation of human antibodies for treating TNF-α associated disorders |
US15/095,393 Expired - Lifetime US9950066B2 (en) | 2002-08-16 | 2016-04-11 | Formulation of human antibodies for treating TNF-alpha associated disorders |
US15/418,460 Expired - Lifetime US9750808B2 (en) | 2002-08-16 | 2017-01-27 | Formulation of human antibodies for treating TNF-alpha associated disorders |
US15/418,469 Expired - Lifetime US9738714B2 (en) | 2002-08-16 | 2017-01-27 | Formulation of human antibodies for treating TNF-alpha associated disorders |
US15/418,465 Expired - Lifetime US9732152B2 (en) | 2002-08-16 | 2017-01-27 | Formulation of human antibodies for treating TNF-alpha associated disorders |
US15/918,663 Abandoned US20190054171A1 (en) | 2002-08-16 | 2018-03-12 | Formulation of human antibodies for treating tnf-alpha associated disorders |
US16/057,217 Abandoned US20180339046A1 (en) | 2002-08-16 | 2018-08-07 | Formulation of human antibodies for treating tnf-alpha associated disorders |
US17/126,500 Abandoned US20210113694A1 (en) | 2002-08-16 | 2020-12-18 | Formulation of human antibodies for treating tnf-alpha associated disorders |
US17/472,004 Pending US20220241415A1 (en) | 2002-08-16 | 2021-09-10 | Formulation of human antibodies for treating tnf-alpha associated disorders |
Country Status (27)
Country | Link |
---|---|
US (27) | US20040033228A1 (ko) |
EP (5) | EP2363145A1 (ko) |
JP (5) | JP4925582B2 (ko) |
KR (4) | KR101273568B1 (ko) |
CN (4) | CN102078608B (ko) |
AR (2) | AR040881A1 (ko) |
AT (1) | ATE555809T1 (ko) |
AU (1) | AU2003267744C1 (ko) |
BR (1) | BR0313492A (ko) |
CA (9) | CA2882931C (ko) |
CL (1) | CL2010000603A1 (ko) |
CY (2) | CY1113353T1 (ko) |
DK (2) | DK1528933T3 (ko) |
ES (2) | ES2387616T3 (ko) |
HK (1) | HK1074008A1 (ko) |
IL (2) | IL166809A (ko) |
MX (1) | MXPA05001841A (ko) |
MY (3) | MY163027A (ko) |
NZ (1) | NZ538030A (ko) |
PE (1) | PE20040994A1 (ko) |
PL (3) | PL218221B1 (ko) |
PT (2) | PT2359856T (ko) |
SI (2) | SI1528933T1 (ko) |
TW (1) | TWI331532B (ko) |
UY (1) | UY27940A1 (ko) |
WO (1) | WO2004016286A2 (ko) |
ZA (1) | ZA200501032B (ko) |
Cited By (107)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20030235585A1 (en) * | 2001-06-08 | 2003-12-25 | Fischkoff Steven A. | Methods of administering anti-TNFalpha antibodies |
US20040009172A1 (en) * | 2002-04-26 | 2004-01-15 | Steven Fischkoff | Use of anti-TNFalpha antibodies and another drug |
US20040126372A1 (en) * | 2002-07-19 | 2004-07-01 | Abbott Biotechnology Ltd. | Treatment of TNFalpha related disorders |
US20040166111A1 (en) * | 2002-10-24 | 2004-08-26 | Zehra Kaymakcalan | Low dose methods for treating disorders in which TNFalpha activity is detrimental |
WO2005063291A1 (ja) * | 2003-12-25 | 2005-07-14 | Kirin Beer Kabushiki Kaisha | 抗体を含有する安定な水性医薬製剤 |
US20060009385A1 (en) * | 2004-04-09 | 2006-01-12 | Abbott Biotechnology Ltd. | Multiple-variable dose regimen for treating TNFalpha-related disorders |
US20060083741A1 (en) * | 2004-10-08 | 2006-04-20 | Hoffman Rebecca S | Treatment of respiratory syncytial virus (RSV) infection |
US20060153846A1 (en) * | 2002-08-16 | 2006-07-13 | Hans-Juergen Krause | Formulation of human antibodies for treating tnf-alpha associated disorders |
US20060269543A1 (en) * | 2005-05-19 | 2006-11-30 | Amgen Inc. | Compositions and methods for increasing the stability of antibodies |
US20070041905A1 (en) * | 2005-08-19 | 2007-02-22 | Hoffman Rebecca S | Method of treating depression using a TNF-alpha antibody |
US20070071747A1 (en) * | 2005-05-16 | 2007-03-29 | Hoffman Rebecca S | Use of TNFalpha inhibitor for treatment of erosive polyarthritis |
EP1798504A1 (en) * | 2005-12-19 | 2007-06-20 | Koninklijke Philips Electronics N.V. | Method of making dried particles |
US20070172897A1 (en) * | 2005-11-01 | 2007-07-26 | Maksymowych Walter P | Methods and compositions for diagnosing ankylosing spondylitis using biomarkers |
US20070249813A1 (en) * | 1996-02-09 | 2007-10-25 | Salfeld Jochen G | Human antibodies that bind human TNFa |
US20070292442A1 (en) * | 2006-04-05 | 2007-12-20 | Min Wan | Antibody purification |
US20080112953A1 (en) * | 2006-10-06 | 2008-05-15 | Amgen Inc. | Stable formulations |
US20080118496A1 (en) * | 2006-04-10 | 2008-05-22 | Medich John R | Uses and compositions for treatment of juvenile rheumatoid arthritis |
WO2008063213A2 (en) | 2006-04-10 | 2008-05-29 | Abbott Biotechnology Ltd. | Uses and compositions for treatment of psoriatic arthritis |
US20080124326A1 (en) * | 2006-10-20 | 2008-05-29 | Amgen Inc. | Stable polypeptide formulations |
US20080131374A1 (en) * | 2006-04-19 | 2008-06-05 | Medich John R | Uses and compositions for treatment of rheumatoid arthritis |
US20080166348A1 (en) * | 2006-04-10 | 2008-07-10 | Hartmut Kupper | Uses and compositions for treatment of rheumatoid arthritis |
US20080311043A1 (en) * | 2006-06-08 | 2008-12-18 | Hoffman Rebecca S | Uses and compositions for treatment of psoriatic arthritis |
WO2008154543A2 (en) | 2007-06-11 | 2008-12-18 | Abbott Biotechnology Ltd. | Methods for treating juvenile idiopathic arthritis |
US20090017472A1 (en) * | 2007-05-31 | 2009-01-15 | Bruno Stuhlmuller | BIOMARKERS PREDICTIVE OF THE RESPONSIVENESS TO TNFalpha INHIBITORS IN AUTOIMMUNE DISORDERS |
US20090110679A1 (en) * | 2007-07-13 | 2009-04-30 | Luk-Chiu Li | Methods and compositions for pulmonary administration of a TNFa inhibitor |
US20090214535A1 (en) * | 2005-06-10 | 2009-08-27 | Chugai Seiyaku Kabushiki Kaisha | Pharmaceutical Compositions Containing sc(Fv)2 |
US7588761B2 (en) | 1996-02-09 | 2009-09-15 | Abbott Biotechnology Ltd. | Human antibodies that bind human TNFα |
US20090271164A1 (en) * | 2008-01-03 | 2009-10-29 | Peng Joanna Z | Predicting long-term efficacy of a compound in the treatment of psoriasis |
US20090280065A1 (en) * | 2006-04-10 | 2009-11-12 | Willian Mary K | Uses and Compositions for Treatment of Psoriasis |
US20090317399A1 (en) * | 2006-04-10 | 2009-12-24 | Pollack Paul F | Uses and compositions for treatment of CROHN'S disease |
US20100021451A1 (en) * | 2006-06-08 | 2010-01-28 | Wong Robert L | Uses and compositions for treatment of ankylosing spondylitis |
US20100034823A1 (en) * | 2006-10-27 | 2010-02-11 | Borhani David W | Crystalline anti-hTNFalpha antibodies |
US20100160894A1 (en) * | 2006-06-30 | 2010-06-24 | Julian Joseph F | Automatic injection device |
EP2231175A2 (en) | 2007-11-30 | 2010-09-29 | Abbott Laboratories | Protein formulations and methods of making same |
US20100266613A1 (en) * | 2009-04-16 | 2010-10-21 | Harding Fiona A | Anti-tnf-alpha antibodies and their uses |
US20100278822A1 (en) * | 2009-05-04 | 2010-11-04 | Abbott Biotechnology, Ltd. | Stable high protein concentration formulations of human anti-tnf-alpha-antibodies |
US20110054414A1 (en) * | 2009-04-29 | 2011-03-03 | Abbott Biotechnology Ltd. | Automatic Injection Device |
US20110150891A1 (en) * | 2009-12-16 | 2011-06-23 | Philip Bosch | Methods of Treating Interstitial Cystitis |
US20110171227A1 (en) * | 2006-04-10 | 2011-07-14 | Okun Martin M | Methods and compositions for treatment of skin disorders |
US20110178500A1 (en) * | 2009-12-15 | 2011-07-21 | Shang Sherwin S | Firing button for automatic injection device |
WO2011153477A2 (en) | 2010-06-03 | 2011-12-08 | Abbott Biotechnology Ltd. | Uses and compositions for treatment of hidradenitis suppurativa (hs) |
US8162887B2 (en) | 2004-06-23 | 2012-04-24 | Abbott Biotechnology Ltd. | Automatic injection devices |
RU2470628C2 (ru) * | 2007-12-28 | 2012-12-27 | Биоинвент Интернешнл Аб | Состав |
WO2013009843A1 (en) * | 2011-07-11 | 2013-01-17 | Camas Incorporated | Compositions against bacterial toxins |
EP2666479A2 (en) | 2006-04-10 | 2013-11-27 | Abbott Biotechnology Ltd | Uses and compositions for treatment of juvenile rheumatoid arthritis |
EP2666480A2 (en) | 2006-04-10 | 2013-11-27 | Abbott Biotechnology Ltd | Uses and compositions for treatment of Crohn's desease |
WO2013186230A1 (en) * | 2012-06-12 | 2013-12-19 | Boehringer Ingelheim International Gmbh | Pharmaceutical formulation for a therapeutic antibody |
EP2676677A1 (en) * | 2011-02-17 | 2013-12-25 | Kyowa Hakko Kirin Co., Ltd. | Highly concentrated anti-cd40 antibody pharmaceutical preparation |
US8658773B2 (en) | 2011-05-02 | 2014-02-25 | Immunomedics, Inc. | Ultrafiltration concentration of allotype selected antibodies for small-volume administration |
US8753839B2 (en) | 2007-08-08 | 2014-06-17 | Abbvie Inc. | Compositions and methods for crystallizing antibodies |
WO2014114651A1 (en) * | 2013-01-24 | 2014-07-31 | Glaxosmithkline Intellectual Property Development Limited | Tnf-alpha antigen-binding proteins |
US8821865B2 (en) | 2010-11-11 | 2014-09-02 | Abbvie Biotechnology Ltd. | High concentration anti-TNFα antibody liquid formulations |
WO2014144960A2 (en) | 2013-03-15 | 2014-09-18 | Abbvie Biotherapeutics Inc. | Fc variants |
US8883146B2 (en) | 2007-11-30 | 2014-11-11 | Abbvie Inc. | Protein formulations and methods of making same |
US8921526B2 (en) | 2013-03-14 | 2014-12-30 | Abbvie, Inc. | Mutated anti-TNFα antibodies and methods of their use |
US8946395B1 (en) | 2013-10-18 | 2015-02-03 | Abbvie Inc. | Purification of proteins using hydrophobic interaction chromatography |
WO2015035044A2 (en) | 2013-09-04 | 2015-03-12 | Abbvie Biotherapeutics Inc. | Fc VARIANTS WITH IMPROVED ANTIBODY-DEPENDENT CELL-MEDIATED CYTOTOXICITY |
US9017687B1 (en) | 2013-10-18 | 2015-04-28 | Abbvie, Inc. | Low acidic species compositions and methods for producing and using the same using displacement chromatography |
US9062106B2 (en) | 2011-04-27 | 2015-06-23 | Abbvie Inc. | Methods for controlling the galactosylation profile of recombinantly-expressed proteins |
US9067990B2 (en) | 2013-03-14 | 2015-06-30 | Abbvie, Inc. | Protein purification using displacement chromatography |
US9085618B2 (en) | 2013-10-18 | 2015-07-21 | Abbvie, Inc. | Low acidic species compositions and methods for producing and using the same |
US9150645B2 (en) | 2012-04-20 | 2015-10-06 | Abbvie, Inc. | Cell culture methods to reduce acidic species |
US9181572B2 (en) | 2012-04-20 | 2015-11-10 | Abbvie, Inc. | Methods to modulate lysine variant distribution |
US9181337B2 (en) | 2013-10-18 | 2015-11-10 | Abbvie, Inc. | Modulated lysine variant species compositions and methods for producing and using the same |
US9193787B2 (en) | 2012-04-20 | 2015-11-24 | Abbvie Inc. | Human antibodies that bind human TNF-alpha and methods of preparing the same |
EP2946767A1 (en) * | 2014-05-23 | 2015-11-25 | Ares Trading S.A. | Liquid pharmaceutical composition |
US9206390B2 (en) | 2012-09-02 | 2015-12-08 | Abbvie, Inc. | Methods to control protein heterogeneity |
US9234033B2 (en) | 2012-09-02 | 2016-01-12 | Abbvie, Inc. | Methods to control protein heterogeneity |
US9249182B2 (en) | 2012-05-24 | 2016-02-02 | Abbvie, Inc. | Purification of antibodies using hydrophobic interaction chromatography |
US20160031982A1 (en) * | 2012-09-07 | 2016-02-04 | Coherus Biosciences, Inc. | Stable Aqueous Formulations of Adalimumab |
US9279015B2 (en) | 2006-04-10 | 2016-03-08 | Robert L. Wong | Methods for treatment of ankylosing spondylitis using TNF alpha antibodies |
US9278131B2 (en) | 2012-08-10 | 2016-03-08 | Adocia | Process for lowering the viscosity of highly concentrated protein solutions |
EP3003369A1 (en) * | 2013-05-28 | 2016-04-13 | Momenta Pharmaceuticals, Inc. | Pharmaceutical compositions comprising pyrophosphate |
EP3009450A1 (en) * | 2011-07-19 | 2016-04-20 | Glaxo Group Limited | Liquid formulation comprising adalimumab and an acetate buffer |
US9326935B2 (en) * | 2013-11-08 | 2016-05-03 | Eli Lilly And Company | Atomoxetine solution |
EP2892559A4 (en) * | 2012-09-05 | 2016-05-11 | Tracon Pharmaceuticals Inc | ANTIBODY FORMULATIONS AND USES THEREOF |
US20160136280A1 (en) * | 2013-06-24 | 2016-05-19 | Hoffmann-La Roche Inc. | Stable intravenous formulation |
EP3053573A1 (en) * | 2015-02-06 | 2016-08-10 | Ares Trading S.A. | Liquid pharmaceutical composition |
US9480743B2 (en) | 2010-12-28 | 2016-11-01 | Hexal Ag | Pharmaceutical formulation comprising a biopharmaceutical drug |
US9493569B2 (en) | 2005-03-31 | 2016-11-15 | Chugai Seiyaku Kabushiki Kaisha | Structural isomers of sc(Fv)2 |
US9499614B2 (en) | 2013-03-14 | 2016-11-22 | Abbvie Inc. | Methods for modulating protein glycosylation profiles of recombinant protein therapeutics using monosaccharides and oligosaccharides |
US9518122B2 (en) | 2009-09-30 | 2016-12-13 | Tracon Pharmaceuticals, Inc. | Endoglin antibodies |
US9550826B2 (en) | 2013-11-15 | 2017-01-24 | Abbvie Inc. | Glycoengineered binding protein compositions |
US9598667B2 (en) | 2013-10-04 | 2017-03-21 | Abbvie Inc. | Use of metal ions for modulation of protein glycosylation profiles of recombinant proteins |
US9610301B2 (en) | 2008-01-15 | 2017-04-04 | Abbvie Deutschland Gmbh & Co Kg | Powdered protein compositions and methods of making same |
US9878102B2 (en) | 2011-01-24 | 2018-01-30 | Abbvie Biotechnology Ltd. | Automatic injection devices having overmolded gripping surfaces |
US9926375B2 (en) | 2014-11-12 | 2018-03-27 | Tracon Pharmaceuticals, Inc. | Anti-endoglin antibodies and uses thereof |
US10005835B2 (en) | 2013-04-29 | 2018-06-26 | Sanofi | Anti-IL-4/anti-IL-13 bispecific antibody formulations |
US20180194843A1 (en) * | 2003-02-10 | 2018-07-12 | Biogen Ma Inc. | Immunoglobulin formulation and method of preparation thereof |
EP3360596A1 (en) | 2010-04-21 | 2018-08-15 | AbbVie Biotechnology Ltd. | Wearable automatic injection device for controlled delivery of therapeutic agents |
WO2018184693A1 (en) * | 2017-04-07 | 2018-10-11 | Ares Trading S.A. | Liquid pharmaceutical composition |
US10155820B2 (en) | 2014-11-12 | 2018-12-18 | Tracon Pharmaceuticals, Inc. | Anti-endoglin antibodies and uses thereof |
US10179811B2 (en) | 2015-04-10 | 2019-01-15 | Fresenius Kabi Deutschland Gmbh | Methods of treating Crohn's disease or ulcerative colitis using an induction dosing regimen comprising anti-TNF-alpha antibody |
US10307483B2 (en) | 2016-10-21 | 2019-06-04 | Amgen Inc. | Pharmaceutical formulations and methods of making the same |
US10322176B2 (en) | 2002-03-01 | 2019-06-18 | Immunomedics, Inc. | Subcutaneous administration of anti-CD74 antibody for systemic lupus erythematosus |
US10426832B2 (en) | 2014-05-23 | 2019-10-01 | Fresenius Kabi Deutschland Gmbh | Liquid pharmaceutical composition |
US10493152B2 (en) | 2014-05-23 | 2019-12-03 | Fresenius Kabi Deutschland Gmbh | Adalimumab formulations |
US10799597B2 (en) | 2017-04-03 | 2020-10-13 | Immunomedics, Inc. | Subcutaneous administration of antibody-drug conjugates for cancer therapy |
US11008389B2 (en) | 2011-03-16 | 2021-05-18 | Sanofi | Uses of a dual V region antibody-like protein |
US11071782B2 (en) | 2016-04-20 | 2021-07-27 | Coherus Biosciences, Inc. | Method of filling a container with no headspace |
US11180559B2 (en) | 2005-03-03 | 2021-11-23 | Immunomedics, Inc. | Subcutaneous anti-HLA-DR monoclonal antibody for treatment of hematologic malignancies |
US11229702B1 (en) | 2015-10-28 | 2022-01-25 | Coherus Biosciences, Inc. | High concentration formulations of adalimumab |
US11534403B2 (en) | 2017-03-06 | 2022-12-27 | Arecor Limited | Liquid pharmaceutical composition |
US11534402B2 (en) | 2017-03-06 | 2022-12-27 | Arecor Limited | Liquid pharmaceutical composition |
US11607451B2 (en) | 2005-06-14 | 2023-03-21 | Amgen Inc. | Self-buffering antibody formulations |
US11608357B2 (en) | 2018-08-28 | 2023-03-21 | Arecor Limited | Stabilized antibody protein solutions |
US11634485B2 (en) | 2019-02-18 | 2023-04-25 | Eli Lilly And Company | Therapeutic antibody formulation |
Families Citing this family (122)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20040002451A1 (en) * | 2002-06-20 | 2004-01-01 | Bruce Kerwin | Compositions of pegylated soluble tumor necrosis factor receptors and methods of preparing |
TW200621282A (en) | 2004-08-13 | 2006-07-01 | Wyeth Corp | Stabilizing formulations |
JO3000B1 (ar) | 2004-10-20 | 2016-09-05 | Genentech Inc | مركبات أجسام مضادة . |
GT200600031A (es) | 2005-01-28 | 2006-08-29 | Formulacion anticuerpo anti a beta | |
AU2006259536A1 (en) * | 2005-06-15 | 2006-12-28 | Schering Corporation | Anti-IGF1R antibody formulations |
US9309316B2 (en) | 2005-12-20 | 2016-04-12 | Bristol-Myers Squibb Company | Stable subcutaneous protein formulations and uses thereof |
US8168760B2 (en) | 2007-03-29 | 2012-05-01 | Abbott Laboratories | Crystalline anti-human IL-12 antibodies |
CA2682730A1 (en) * | 2007-04-11 | 2008-10-23 | Alcon Research, Ltd. | Use of an inhibitor of tnf.alpha. plus an antihistamine to treat allergic rhinitis and allergic conjunctivitis |
SI2235059T1 (sl) | 2007-12-26 | 2015-06-30 | Xencor, Inc. | Fc variante s spremenjeno vezjo na fcrn |
EP2225276B1 (en) | 2007-12-31 | 2014-04-23 | Bayer Intellectual Property GmbH | Antibodies to tnf alpha |
KR20110014607A (ko) | 2008-04-29 | 2011-02-11 | 아보트 러보러터리즈 | 이원 가변 도메인 면역글로불린 및 이의 용도 |
EP2297208A4 (en) | 2008-06-03 | 2012-07-11 | Abbott Lab | DUAL VARIABLE DOMAIN IMMUNOGLOBULINS AND ITS USES |
NZ589434A (en) | 2008-06-03 | 2012-11-30 | Abbott Lab | Dual variable domain immunoglobulins and uses thereof |
CA2729949A1 (en) | 2008-07-08 | 2010-01-14 | Abbott Laboratories | Prostaglandin e2 dual variable domain immunoglobulins and uses thereof |
NZ592644A (en) * | 2008-11-28 | 2013-09-27 | Abbott Lab | Stable antibody compositions and methods for stabilizing same |
WO2011029823A1 (en) | 2009-09-09 | 2011-03-17 | Novartis Ag | Monoclonal antibody reactive with cd63 when expressed at the surface of degranulated mast cells |
BR112012007091A2 (pt) * | 2009-10-01 | 2016-04-19 | Alcon Res Ltd | composições de olopatadina e seus usos |
MX2012004415A (es) | 2009-10-15 | 2012-05-08 | Abbott Lab | Inmunoglobulinas de dominio variable doble y usos de las mismas. |
UY32979A (es) | 2009-10-28 | 2011-02-28 | Abbott Lab | Inmunoglobulinas con dominio variable dual y usos de las mismas |
FR2958646B1 (fr) * | 2010-04-07 | 2012-05-18 | Adocia | Polysaccharides comportant des groupes fonctionnels carboxyles substitues par un derive d'acide hydrophobe. |
EP3708190A1 (en) | 2010-02-26 | 2020-09-16 | Novo Nordisk A/S | Stable antibody containing compositions |
CA3101298A1 (en) | 2010-03-01 | 2011-09-09 | Bayer Healthcare Llc | Optimized monoclonal antibodies against tissue factor pathway inhibitor (tfpi) |
CN102869345B (zh) | 2010-03-17 | 2015-02-11 | 诺瓦利克有限责任公司 | 用于治疗眼内压增高的药物组合物 |
US20130136733A1 (en) | 2010-05-28 | 2013-05-30 | Novo Nordisk A/S | Stable Multi-Dose Compositions Comprising an Antibody and a Preservative |
AU2011285852B2 (en) | 2010-08-03 | 2014-12-11 | Abbvie Inc. | Dual variable domain immunoglobulins and uses thereof |
PE20140229A1 (es) | 2010-08-26 | 2014-03-27 | Abbvie Inc | Inmunoglobulinas con dominio variable dual y usos de las mismas |
CN103154037A (zh) | 2010-10-05 | 2013-06-12 | 诺瓦提斯公司 | 抗IL12Rβ1抗体及它们在治疗自身免疫病和炎性疾病中的用途 |
EP2444063A1 (en) | 2010-10-20 | 2012-04-25 | Novaliq GmbH | Liquid pharmaceutical compositions for the delivery of active ingredients |
UY34054A (es) * | 2011-05-02 | 2012-11-30 | Millennium Pharm Inc | FORMULACIÓN PARA ANTICUERPO ANTI-a(alfa)4B(Beta)7 |
AR087305A1 (es) | 2011-07-28 | 2014-03-12 | Regeneron Pharma | Formulaciones estabilizadas que contienen anticuerpos anti-pcsk9, metodo de preparacion y kit |
SG11201401360XA (en) | 2011-10-25 | 2014-05-29 | Onclave Therapeutics Ltd | Antibody formulations and methods |
AU2012362326A1 (en) | 2011-12-30 | 2014-07-24 | Abbvie Inc. | Dual variable domain immunoglobulins against IL-13 and/or IL-17 |
KR101989648B1 (ko) | 2012-01-23 | 2019-06-14 | 노바리크 게엠베하 | 부분불소화 알칸에 기초한 안정화된 단백질 조성물 |
MX363700B (es) * | 2012-03-07 | 2019-03-29 | Cadila Healthcare Ltd | Formulaciones farmaceuticas de anticuerpos tnf-alfa. |
ES2702246T3 (es) * | 2012-03-26 | 2019-02-28 | Sanofi Sa | Formulaciones de agente de unión IgG4 estables |
US9592289B2 (en) * | 2012-03-26 | 2017-03-14 | Sanofi | Stable IgG4 based binding agent formulations |
US9592297B2 (en) | 2012-08-31 | 2017-03-14 | Bayer Healthcare Llc | Antibody and protein formulations |
CA2883002C (en) | 2012-09-12 | 2019-05-21 | Novaliq Gmbh | Compositions comprising mixtures of semifluorinated alkanes |
ES2965828T3 (es) | 2012-09-12 | 2024-04-17 | Novaliq Gmbh | Composiciones de alcano semifluorado |
JP6431844B2 (ja) * | 2012-10-26 | 2018-11-28 | ルピン アトランティス ホールディングス エスエーLupin Atlantis Holdings Sa | Tnfr:fc融合プロテインの安定な医薬組成物 |
SG11201503412RA (en) | 2012-11-01 | 2015-05-28 | Abbvie Inc | Anti-vegf/dll4 dual variable domain immunoglobulins and uses thereof |
WO2014099636A1 (en) * | 2012-12-18 | 2014-06-26 | Merck Sharp & Dohme Corp. | Liquid formulations for an anti-tnf alpha antibody |
CN102988984B (zh) * | 2012-12-21 | 2015-05-20 | 嘉和生物药业有限公司 | 增强稳定性的抗TNF-α人单克隆抗体的含水药物制剂 |
UY35315A (es) | 2013-02-08 | 2014-09-30 | Novartis Ag | Anticuerpos anti-il-17a y su uso en el tratamiento de trastornos autoinmunes e inflamatorios |
CA2899449A1 (en) | 2013-03-14 | 2014-10-02 | Abbvie Inc. | Low acidic species compositions and methods for producing the same using displacement chromatography |
BR112015017307A2 (pt) | 2013-03-14 | 2017-11-21 | Abbvie Inc | composições de espécies com baixa acidez e métodos para produção e uso das mesmas |
WO2014141149A1 (en) * | 2013-03-15 | 2014-09-18 | Glaxosmithkline Intellectual Property (No.2) Limited | Formulations with reduced viscosity |
JP2016522793A (ja) | 2013-03-15 | 2016-08-04 | アッヴィ・インコーポレイテッド | IL−1βおよび/またはIL−17に対して指向された二重特異的結合タンパク質 |
CN103446583B (zh) * | 2013-03-21 | 2015-11-18 | 百奥泰生物科技(广州)有限公司 | 一种治疗TNF-α相关疾病的人抗体制剂 |
CN105377237B (zh) | 2013-07-19 | 2019-04-19 | 德国赫素制药集团 | 使免疫反应的调节与生物药品的给药相关的方法和制剂 |
US10273298B2 (en) * | 2013-07-23 | 2019-04-30 | Novaliq Gmbh | Stabilized antibody compositions |
JP6526025B2 (ja) | 2013-10-16 | 2019-06-05 | オンコバイオロジクス,インコーポレイティド | 抗体安定性を増強する緩衝液製剤 |
EP3071237B1 (en) | 2013-11-21 | 2024-06-26 | Genmab A/S | Antibody-drug conjugate lyophilised formulation |
CN104666242B (zh) * | 2013-11-26 | 2018-01-02 | 信达生物制药(苏州)有限公司 | 一种稳定的抗TNF‑α抗体制剂及其用途 |
CN104707146B (zh) * | 2013-12-16 | 2019-04-16 | 浙江海正药业股份有限公司 | 一种含有阿达木单抗的药物组合物 |
EP2960252A1 (en) * | 2014-06-26 | 2015-12-30 | Institut Pasteur | Phospholipase for treatment of immunosuppression |
CA2944330A1 (en) | 2014-04-02 | 2015-10-08 | Intas Pharmaceuticals Limited | Liquid pharmaceutical composition of adalimumab |
CN105012949A (zh) * | 2014-04-28 | 2015-11-04 | 上海药明康德新药开发有限公司 | 重组人抗人TNFα单克隆抗体的制剂 |
EP3161001A2 (en) | 2014-06-25 | 2017-05-03 | Novartis AG | Antibodies specific for il-17a fused to hyaluronan binding peptide tags |
US20170226552A1 (en) | 2014-07-03 | 2017-08-10 | Abbvie Inc. | Methods for modulating protein glycosylation profiles of recombinant protein therapeutics using cobalt |
US20160185848A1 (en) | 2014-07-09 | 2016-06-30 | Abbvie Inc. | Methods for modulating the glycosylation profile of recombinant proteins using sugars |
TWI711629B (zh) | 2014-09-03 | 2020-12-01 | 德商包林格因蓋爾漢國際股份有限公司 | 靶向IL-23A與TNF-α之化合物及其用途 |
US9821059B2 (en) * | 2014-10-17 | 2017-11-21 | Alteogen Inc. | Composition for stabilizing protein and pharmaceutical formulation comprising the same |
HUP1400510A1 (hu) * | 2014-10-28 | 2016-05-30 | Richter Gedeon Nyrt | Gyógyászati TNFalfa ellenes antitest készítmény |
WO2016094881A2 (en) | 2014-12-11 | 2016-06-16 | Abbvie Inc. | Lrp-8 binding proteins |
WO2016103093A1 (en) | 2014-12-23 | 2016-06-30 | Pfizer Inc. | Stable aqueous antibody formulation for anti tnf alpha antibodies |
WO2016118707A1 (en) | 2015-01-21 | 2016-07-28 | Oncobiologics, Inc. | Modulation of charge variants in a monoclonal antibody composition |
WO2016162819A1 (en) | 2015-04-07 | 2016-10-13 | Lupin Limited | Stable aqueous pharmaceutical composition of anti-tnf alpha antibody |
TW201710286A (zh) | 2015-06-15 | 2017-03-16 | 艾伯維有限公司 | 抗vegf、pdgf及/或其受體之結合蛋白 |
KR20180018538A (ko) | 2015-06-17 | 2018-02-21 | 제넨테크, 인크. | Pd-1 축 결합 길항제 및 탁산을 사용하여 국소적 진행성 또는 전이성 유방암을 치료하는 방법 |
US20170028013A1 (en) * | 2015-07-30 | 2017-02-02 | Teva Pharmaceutical Industries, Ltd. | Combination formulation of laquinimod and glatiramer acetate with amino acids |
US10772956B2 (en) | 2015-08-18 | 2020-09-15 | Regeneron Pharmaceuticals, Inc. | Methods for reducing or eliminating the need for lipoprotein apheresis in patients with hyperlipidemia by administering alirocumab |
CN110403923B (zh) | 2015-09-30 | 2021-09-21 | 诺瓦利克有限责任公司 | 半氟化化合物和其组合物 |
EP3722274B1 (en) | 2015-09-30 | 2023-06-07 | Novaliq GmbH | 2-perfluorobutyl pentane for ophthalmic administration |
US11583584B1 (en) * | 2015-10-28 | 2023-02-21 | Coherus Biosciences, Inc. | Stable protein compositions and methods of their use |
KR102386735B1 (ko) * | 2015-11-06 | 2022-04-14 | 주식회사 제넥신 | 변형된 인터루킨-7 융합 단백질의 제형 |
WO2017083525A1 (en) | 2015-11-11 | 2017-05-18 | Opi Vi- Ip Holdco Llc | Composition and methods for anti-tnfr2 antibodies |
US20170189548A1 (en) | 2015-11-25 | 2017-07-06 | Immunogen, Inc. | Pharmaceutical formulations and methods of use thereof |
IL260218B2 (en) | 2016-01-11 | 2023-04-01 | Novartis Ag | Humanized monoclonal antibodies that elicit an immune response against interleukin-2, and their fusion proteins |
RU2736830C2 (ru) * | 2016-01-12 | 2020-11-20 | Др. Редди'С Лабораторис Лимитед | Стабильная фармацевтическая композиция |
SG11201805534TA (en) | 2016-01-13 | 2018-07-30 | Genmab As | Formulation for antibody and drug conjugate thereof |
AU2017213775A1 (en) | 2016-02-03 | 2018-08-16 | Outlook Therapeutics, Inc. | Buffer formulations for enhanced antibody stability |
US20180043020A1 (en) * | 2016-04-20 | 2018-02-15 | Coherus Biosciences, Inc. | Method of reducing immunogenicity of drug products |
DK3442480T3 (da) | 2016-06-23 | 2020-01-13 | Novaliq Gmbh | Fremgangsmåde til topisk indgivelse |
HUP1600456A2 (en) | 2016-07-19 | 2018-01-29 | Richter Gedeon Nyrt | Novel cell-based tnf-alpha binding assay |
ES2969758T3 (es) | 2016-09-22 | 2024-05-22 | Novaliq Gmbh | Composiciones farmacéuticas para usar en la terapia de la blefaritis |
CN109906085B (zh) | 2016-09-23 | 2024-03-08 | 诺瓦利克有限责任公司 | 含有环孢素的眼用组合物 |
JOP20190162A1 (ar) | 2016-12-30 | 2019-06-27 | Biocad Joint Stock Co | تركيبة صيدلانية مائية من جسم مضاد لـ tnf? أحادي النسيلة معاود الارتباط الجيني |
AU2018207367B2 (en) | 2017-01-11 | 2024-02-15 | Celltrion Inc. | Stable Liquid Formula |
AU2018253944B2 (en) | 2017-04-21 | 2022-09-15 | Dermaliq Therapeutics, Inc. | Iodine compositions |
CN106918633B (zh) * | 2017-04-24 | 2019-06-25 | 中国科学院苏州生物医学工程技术研究所 | 基于适体和金磁纳米颗粒的细胞因子TNF-α的检测方法 |
JOP20190260A1 (ar) | 2017-05-02 | 2019-10-31 | Merck Sharp & Dohme | صيغ ثابتة لأجسام مضادة لمستقبل الموت المبرمج 1 (pd-1) وطرق استخدامها |
US11845798B2 (en) | 2017-05-02 | 2023-12-19 | Merck Sharp & Dohme Llc | Formulations of anti-LAG3 antibodies and co-formulations of anti-LAG3 antibodies and anti-PD-1 antibodies |
EP3621601A1 (en) | 2017-05-12 | 2020-03-18 | Novaliq GmbH | Pharmaceutical compositions comprosing semifluorinated alkanes for the treatment of contact lense-related conditions |
US11136138B2 (en) | 2017-07-10 | 2021-10-05 | Autel Robotics Co., Ltd. | Aircraft control method and apparatus and aircraft |
JP2020534366A (ja) * | 2017-09-20 | 2020-11-26 | アルヴォテック エイチエフ | アダリムマブ用医薬製剤 |
US11723861B2 (en) | 2017-09-27 | 2023-08-15 | Novaliq Gmbh | Ophthalmic compositions comprising latanoprost for use in the treatment of ocular diseases |
US11896559B2 (en) | 2017-10-04 | 2024-02-13 | Novaliq Gmbh | Opthalmic compositions comprising F6H8 |
MX2017016884A (es) * | 2017-12-19 | 2019-06-20 | Probiomed S A De C V | Formulacion farmaceutica estable de una proteina anti-tnfa. |
WO2019126536A1 (en) | 2017-12-20 | 2019-06-27 | Alexion Pharmaceuticals Inc. | Humanized anti-cd200 antibodies and uses thereof |
WO2019126133A1 (en) * | 2017-12-20 | 2019-06-27 | Alexion Pharmaceuticals, Inc. | Liquid formulations of anti-cd200 antibodies |
CN108414479A (zh) * | 2018-01-19 | 2018-08-17 | 祝胜郎 | 一种免疫组合物在制备IgA肾病无创检测用试剂中的用途 |
US20210031012A1 (en) | 2018-01-26 | 2021-02-04 | Progenity, Inc. | Treatment of a disease of the gastrointestinal tract with a pde4 inhibitor |
CN110151988A (zh) * | 2018-02-11 | 2019-08-23 | 百奥泰生物制药股份有限公司 | 一种靶向治疗TNF-α相关疾病的人抗体制剂 |
CN110302377B (zh) * | 2018-02-11 | 2020-04-17 | 百奥泰生物制药股份有限公司 | 一种靶向治疗TNF-α相关疾病的人抗体制剂 |
SG11202007858VA (en) | 2018-03-02 | 2020-09-29 | Novaliq Gmbh | Pharmaceutical compositions comprising nebivolol |
US20210363233A1 (en) | 2018-06-20 | 2021-11-25 | Progenity, Inc. | Treatment of a disease of the gastrointestinal tract with an il-12/il-23 inhibitor |
EP3810095A1 (en) | 2018-06-20 | 2021-04-28 | Progenity, Inc. | Treatment of a disease of the gastrointestinal tract with a tnf inhibitor |
WO2019246312A1 (en) | 2018-06-20 | 2019-12-26 | Progenity, Inc. | Treatment of a disease of the gastrointestinal tract with an immunomodulator |
US20230009902A1 (en) | 2018-06-20 | 2023-01-12 | Progenity, Inc. | Treatment of a disease or condition in a tissue orginating from the endoderm |
EP3810085A1 (en) | 2018-06-20 | 2021-04-28 | Progenity, Inc. | Treatment of a disease of the gastrointestinal tract with an integrin inhibitor |
WO2019246273A1 (en) | 2018-06-20 | 2019-12-26 | Progenity, Inc. | Treatment of a disease of the gastrointestinal tract with a jak or other kinase inhibitor |
SG11202102820VA (en) | 2018-10-12 | 2021-04-29 | Novaliq Gmbh | Ophthalmic composition for treatment of dry eye disease |
WO2020138517A1 (ko) * | 2018-12-24 | 2020-07-02 | 삼성바이오에피스 주식회사 | 항-TNFα 항체를 포함하는 약제학적 조성물 |
WO2021168274A1 (en) | 2020-02-21 | 2021-08-26 | Silverback Therapeutics, Inc. | Nectin-4 antibody conjugates and uses thereof |
WO2021209017A1 (zh) * | 2020-04-17 | 2021-10-21 | 苏州丁孚靶点生物技术有限公司 | 一种特异性结合cd137的制剂及其用途 |
JP2023525825A (ja) * | 2020-05-13 | 2023-06-19 | イノベント バイオロジクス(スーチョウ)カンパニー,リミティド | 抗IL-23p19抗体を含む製剤、その調製方法および使用 |
WO2022006184A2 (en) * | 2020-06-29 | 2022-01-06 | Kodiscovery, Llc | Cellular energy inhibitor formulations for the treatment of pathogenic infections and associated methods |
JP2023532304A (ja) | 2020-07-01 | 2023-07-27 | エーアールエス ファーマシューティカルズ オペレーションズ,インク. | 抗asgr1抗体コンジュゲートおよびその使用 |
WO2022231978A1 (en) * | 2021-04-26 | 2022-11-03 | Truebinding, Inc. | Anti-gal3 antibody formulations and methods of use thereof |
AU2022348349A1 (en) * | 2021-09-16 | 2024-05-02 | Aprogen Inc. | PHARMACEUTICAL COMPOSITION CONTAINING ANTI-TNFα ANTIBODY |
US11773160B1 (en) | 2022-08-05 | 2023-10-03 | Anaveon AG | Immune-stimulating IL-2 fusion proteins |
Family Cites Families (157)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPS605899B2 (ja) | 1975-04-10 | 1985-02-14 | 中外製薬株式会社 | 免疫化学的定量法 |
US4396608A (en) | 1981-08-24 | 1983-08-02 | Cutter Laboratories | Intravenously injectable immune serum globulin |
IE833023L (en) * | 1983-01-28 | 1984-07-28 | Joseph Patrick Mcauliffe | System and process of identifying and updating tuning¹constants |
DE3483784D1 (de) | 1984-07-07 | 1991-01-31 | Woelm Pharma Gmbh & Co | Verfahren zur herstellung von gamma-globulin zur intravenoesen anwendung. |
IL73883A (en) | 1984-12-20 | 1990-12-23 | Yeda Res & Dev | Monoclonal antibodies against tnf-alpha,hybridomas producing them and method for the purification of tnf-alpha |
US4597966A (en) | 1985-01-09 | 1986-07-01 | Ortho Diagnostic Systems, Inc. | Histidine stabilized immunoglobulin and method of preparation |
US4870163A (en) | 1985-08-29 | 1989-09-26 | New York Blood Center, Inc. | Preparation of pure human tumor necrosis factor and hybridomas producing monoclonal antibodies to human tumor necrosis factor |
EP0230574A3 (en) | 1986-01-31 | 1989-03-22 | Yale University | Pharmaceutical compositions against infections caused by lav/htlv iii virus and the use thereof |
DE3631229A1 (de) | 1986-09-13 | 1988-03-24 | Basf Ag | Monoklonale antikoerper gegen humanen tumornekrosefaktor (tnf) und deren verwendung |
US5237054A (en) | 1987-02-20 | 1993-08-17 | Akzo Pharma | Stabilized aqueous composition containing antibodies |
CA1329760C (en) | 1987-10-29 | 1994-05-24 | Ted C. K. Lee | Plasma and recombinant protein formulations in high ionic strength media |
US4877608A (en) | 1987-11-09 | 1989-10-31 | Rorer Pharmaceutical Corporation | Pharmaceutical plasma protein formulations in low ionic strength media |
US5981485A (en) | 1997-07-14 | 1999-11-09 | Genentech, Inc. | Human growth hormone aqueous formulation |
US5096885A (en) | 1988-04-15 | 1992-03-17 | Genentech, Inc. | Human growth hormone formulation |
WO1989011298A1 (en) | 1988-05-27 | 1989-11-30 | Centocor, Inc. | Formulation for antibody reagents |
EP0394385A1 (en) | 1988-07-27 | 1990-10-31 | BMC Software, Inc. | Improved data transmission optimizer |
US4897465A (en) | 1988-10-12 | 1990-01-30 | Abbott Laboratories | Enrichment and concentration of proteins by ultrafiltration |
EP0374510B1 (en) | 1988-12-19 | 1997-01-15 | American Cyanamid Company | Products for the treatment of endotoxic shock in a mammal |
EP0465513A1 (en) | 1989-03-27 | 1992-01-15 | Centocor, Inc. | FORMULATIONS FOR STABILIZING OF IgM ANTIBODIES |
CA2064915C (en) | 1989-08-07 | 2001-05-29 | Deborah A. Rathjen | Tumour necrosis factor binding ligands |
US5998378A (en) | 1989-08-16 | 1999-12-07 | Chiron Corporation | Compositions for the inhibition of TNF hormone formation and uses thereof |
GB8921123D0 (en) | 1989-09-19 | 1989-11-08 | Millar Ann B | Treatment of ards |
JPH0791318B2 (ja) | 1989-09-21 | 1995-10-04 | 三井東圧化学株式会社 | 蛋白質水溶液、蛋白質水溶液の濃度増大方法および蛋白質製剤 |
US5945098A (en) * | 1990-02-01 | 1999-08-31 | Baxter International Inc. | Stable intravenously-administrable immune globulin preparation |
DE4037604A1 (de) | 1990-04-25 | 1991-10-31 | Bayer Ag | Verwendung von anti-tnf-antikoerpern als arzneimittel bei der behandlung von ischaemien und deren folgen |
WO1992003145A1 (en) | 1990-08-27 | 1992-03-05 | Peptide Technology Ltd. | Method of treating viral infection |
GB9109645D0 (en) | 1991-05-03 | 1991-06-26 | Celltech Ltd | Recombinant antibodies |
JPH0565233A (ja) | 1991-03-08 | 1993-03-19 | Mitsui Toatsu Chem Inc | モノクローナル抗体含有凍結乾燥製剤 |
WO1992016221A1 (en) | 1991-03-15 | 1992-10-01 | Synergen, Inc. | Pegylation of polypeptides |
US20060246073A1 (en) * | 1991-03-18 | 2006-11-02 | Knight David M | Anti-TNF antibodies and peptides of human tumor necrosis factor |
EP0610201B2 (en) | 1991-03-18 | 2007-09-26 | New York University | Monoclonal and chimeric antibodies specific for human tumor necrosis factor |
US6277969B1 (en) | 1991-03-18 | 2001-08-21 | New York University | Anti-TNF antibodies and peptides of human tumor necrosis factor |
JPH06508502A (ja) | 1991-03-29 | 1994-09-29 | イミュネックス・コーポレーション | 単離されたウイルス蛋白質サイトカイン拮抗薬 |
US6165467A (en) | 1991-07-20 | 2000-12-26 | Yoshihide Hagiwara | Stabilized human monoclonal antibody preparation |
GB9122820D0 (en) | 1991-10-28 | 1991-12-11 | Wellcome Found | Stabilised antibodies |
WO1993011793A1 (en) | 1991-12-17 | 1993-06-24 | Schering Corporation | Use of the combination of anti-tumor necrosis factor plus interleukin-6 to treat septic shock |
US5605923A (en) | 1992-04-02 | 1997-02-25 | Smithkline Beecham Corporation | Compounds useful for treating inflammatory diseases and inhibiting production of tumor necrosis factor |
EP0585705B1 (en) | 1992-08-28 | 1998-11-04 | Bayer Corporation | Use of monoclonal antibodies to TNF to treat bacterial meningitis |
AU682156B2 (en) | 1992-10-15 | 1997-09-25 | Dana-Farber Cancer Institute, Inc. | Treatment of insulin resistance in obesity linked type II diabetes using antagonists to TNF-alpha function |
US5358708A (en) | 1993-01-29 | 1994-10-25 | Schering Corporation | Stabilization of protein formulations |
PT614984E (pt) | 1993-03-05 | 2001-12-28 | Bayer Ag | Anticorpos humanos anti-tnf |
DE4307508A1 (de) | 1993-03-10 | 1994-09-15 | Knoll Ag | Verwendung von anti-TNF-Antikörpern als Arzneimittel bei der Behandlung von Herzinsuffizienz (Herzmuskelschwäche) |
FR2708467B1 (fr) | 1993-07-30 | 1995-10-20 | Pasteur Merieux Serums Vacc | Préparations d'immunoglobulines stabilisées et procédé pour leur préparation. |
DE4344824C1 (de) | 1993-12-28 | 1995-08-31 | Immuno Ag | Hochkonzentriertes Immunglobulin-Präparat und Verfahren zu seiner Herstellung |
NZ278607A (en) | 1994-02-07 | 1999-05-28 | Knoll Ag | Use of tnf antagonists for treating disorders involving elevated serum levels of il-6 wherein the serum levels are 500pg/ml or above |
ZA955642B (en) * | 1994-07-07 | 1997-05-06 | Ortho Pharma Corp | Lyophilized imaging agent formulation |
GB9418092D0 (en) | 1994-09-08 | 1994-10-26 | Red Cross Found Cent Lab Blood | Organic compounds |
US5656730A (en) | 1995-04-07 | 1997-08-12 | Enzon, Inc. | Stabilized monomeric protein compositions |
US6267958B1 (en) | 1995-07-27 | 2001-07-31 | Genentech, Inc. | Protein formulation |
AU716785B2 (en) * | 1995-07-27 | 2000-03-09 | Genentech Inc. | Stabile isotonic lyophilized protein formulation |
DE69626829T2 (de) | 1995-08-04 | 2004-03-18 | Lek Farmacevtska Druzba D.D. | Monoklonale antikörper gegen lösliche tnf-alpha rezeptoren p55 und p75 als auch gegen tnf-alpha und dessen analogen |
US6090382A (en) | 1996-02-09 | 2000-07-18 | Basf Aktiengesellschaft | Human antibodies that bind human TNFα |
US5770700A (en) | 1996-01-25 | 1998-06-23 | Genetics Institute, Inc. | Liquid factor IX formulations |
DK0929578T3 (da) | 1996-02-09 | 2003-08-25 | Abbott Lab Bermuda Ltd | Humane antistoffer, der binder human TNFalfa |
GB9610992D0 (en) * | 1996-05-24 | 1996-07-31 | Glaxo Group Ltd | Concentrated antibody preparation |
WO1998004281A1 (en) | 1996-07-26 | 1998-02-05 | Smithkline Beecham Corpration | Improved method of treating immune cell mediated systemic diseases |
EP0852951A1 (de) * | 1996-11-19 | 1998-07-15 | Roche Diagnostics GmbH | Stabile lyophilisierte pharmazeutische Zubereitungen von mono- oder polyklonalen Antikörpern |
GB9705810D0 (en) * | 1997-03-20 | 1997-05-07 | Common Services Agency | Intravenous immune globulin |
EP0973549A2 (en) | 1997-04-07 | 2000-01-26 | Cangene Corporation | Intravenous immune globulin formulation containing a non-ionic surface active agent with improved pharmacokinetic properties |
DE69810481T2 (de) * | 1997-06-13 | 2003-09-25 | Genentech Inc | Stabilisierte antikörperformulierung |
US6171586B1 (en) * | 1997-06-13 | 2001-01-09 | Genentech, Inc. | Antibody formulation |
US6159471A (en) * | 1997-10-23 | 2000-12-12 | Yoshitomi Pharmaceutical Industries, Ltd. | Room temperature storable immunoglobulin preparation for intravenous injection |
PT917879E (pt) | 1997-11-22 | 2002-12-31 | Roche Diagnostics Gmbh | Processo melhorado para estabilizacao de proteinas |
AU2444899A (en) | 1998-01-22 | 1999-08-09 | Astrazeneca Ab | Pharmaceutical formulation comprising an antibody and a citrate buffer |
ES2421736T3 (es) | 1998-06-09 | 2013-09-05 | Csl Behring Ag | Procedimiento para la preparación de inmunoglobulinas para administración intravenosa y otros productos inmunoglobulínicos |
GB9819019D0 (en) | 1998-09-01 | 1998-10-28 | Cerebrus Ltd | Chemical compounds II |
US6379666B1 (en) | 1999-02-24 | 2002-04-30 | Edward L. Tobinick | TNF inhibitors for the treatment of neurological, retinal and muscular disorders |
US6423321B2 (en) | 1999-02-24 | 2002-07-23 | Edward L. Tobinick | Cytokine antagonists for the treatment of sensorineural hearing loss |
US6015557A (en) | 1999-02-24 | 2000-01-18 | Tobinick; Edward L. | Tumor necrosis factor antagonists for the treatment of neurological disorders |
US6419934B1 (en) | 1999-02-24 | 2002-07-16 | Edward L. Tobinick | TNF modulators for treating neurological disorders associated with viral infection |
US6537549B2 (en) | 1999-02-24 | 2003-03-25 | Edward L. Tobinick | Cytokine antagonists for the treatment of localized disorders |
US6177077B1 (en) | 1999-02-24 | 2001-01-23 | Edward L. Tobinick | TNT inhibitors for the treatment of neurological disorders |
US6419944B2 (en) | 1999-02-24 | 2002-07-16 | Edward L. Tobinick | Cytokine antagonists for the treatment of localized disorders |
TR200102715T2 (tr) | 1999-03-25 | 2002-09-23 | Knoll Gmbh | Beşeri IL-12'yi bağlayan beşeri antikorlar ve bunları üretmek için yöntemler. |
WO2000066160A1 (fr) | 1999-04-28 | 2000-11-09 | Yamanouchi Pharmaceutical Co., Ltd. | Composition medicamenteuse parenterale a fragment d'anticorps monoclonal humanise et procede de stabilisation |
CA2371095A1 (en) | 1999-05-05 | 2000-11-16 | Michela Seveso | Enhanced delivery of nucleic acid-based drugs |
AUPQ026799A0 (en) | 1999-05-10 | 1999-06-03 | Csl Limited | Method of increasing protein stability by removing immunoglobulin aggregates |
AU784045B2 (en) | 1999-06-25 | 2006-01-19 | Genentech Inc. | Humanized anti-ErbB2 antibodies and treatment with anti-ErbB2 antibodies |
ATE403437T1 (de) | 1999-12-14 | 2008-08-15 | Genentech Inc | Lfa-1 antagonisten und tnf-alpha antagonisten zur behandlung von rheumatoiden arthritis |
EP1254666A4 (en) | 1999-12-28 | 2004-12-22 | Chugai Pharmaceutical Co Ltd | STABLE ANTIBODY COMPOSITIONS AND INJECTION FORMULATIONS |
US6585957B1 (en) | 2000-01-25 | 2003-07-01 | Aeropharm Technology Incorporated | Medicinal aerosol formulation |
WO2001074811A2 (en) | 2000-03-30 | 2001-10-11 | Takeda Chemical Industries, Ltd. | Substituted 1,3-thiazole compounds, their production and use |
DE10022092A1 (de) * | 2000-05-08 | 2001-11-15 | Aventis Behring Gmbh | Stabilisiertes Protein-Präparat und Verfahren zu seiner Herstellung |
AU750296B2 (en) | 2000-06-23 | 2002-07-11 | F. Hoffmann-La Roche Ag | Antibodies against SEMP1, methods for their production and uses thereof |
AU2001276737A1 (en) * | 2000-08-04 | 2002-02-18 | Chugai Seiyaku Kabushiki Kaisha | Protein injection preparations |
UA81743C2 (uk) * | 2000-08-07 | 2008-02-11 | Центокор, Инк. | МОНОКЛОНАЛЬНЕ АНТИТІЛО ЛЮДИНИ, ЩО СПЕЦИФІЧНО ЗВ'ЯЗУЄТЬСЯ З ФАКТОРОМ НЕКРОЗУ ПУХЛИН АЛЬФА (ФНПα), ФАРМАЦЕВТИЧНА КОМПОЗИЦІЯ, ЩО ЙОГО МІСТИТЬ, ТА СПОСІБ ЛІКУВАННЯ РЕВМАТОЇДНОГО АРТРИТУ |
US6902734B2 (en) * | 2000-08-07 | 2005-06-07 | Centocor, Inc. | Anti-IL-12 antibodies and compositions thereof |
JP5485489B2 (ja) | 2000-08-11 | 2014-05-07 | 中外製薬株式会社 | 抗体含有安定化製剤 |
SE0003045D0 (sv) * | 2000-08-29 | 2000-08-29 | Probi Ab | New method |
DE60139944D1 (de) * | 2000-10-12 | 2009-10-29 | Genentech Inc | Niederviskose konzentrierte proteinformulierungen |
AU3664102A (en) | 2000-12-01 | 2002-06-11 | Battelle Memorial Institute | Method for stabilizing biomolecules in liquid formulations |
IL156618A0 (en) | 2000-12-28 | 2004-01-04 | Altus Biologics Inc | Crystals of whole antibodies and fragments thereof, methods for the preparation thereof and diagnostic kits utilizing the same |
ES2184594B1 (es) | 2001-01-17 | 2004-01-01 | Probitas Pharma Sa | Procedimiento para la produccion de gammaglobulina g humana inactivada de virus. |
KR20020066778A (ko) | 2001-02-13 | 2002-08-21 | 한국과학기술연구원 | 체내 난흡수 물질의 흡수촉진용 조성물과 제형 및 그의제조방법 |
US20140186361A1 (en) | 2012-09-07 | 2014-07-03 | Coherus Biosciences, Inc. | Stable Aqueous Formulations of Adalimumab |
EP1407551A4 (en) | 2001-05-14 | 2005-03-09 | Xyron Corp | DIGITAL / ANALOG CONVERTER |
WO2002096461A1 (en) * | 2001-05-25 | 2002-12-05 | Abbott Gmbh & Co. Kg | Use of anti-tnf antibodies as drugs in treating septic disorders of anemic patients |
EP1391209A4 (en) * | 2001-05-30 | 2009-12-16 | Chugai Pharmaceutical Co Ltd | PROTEIN PREPARATION |
GB0113179D0 (en) * | 2001-05-31 | 2001-07-25 | Novartis Ag | Organic compounds |
CA2868614A1 (en) | 2001-06-08 | 2002-12-08 | Abbott Laboratories (Bermuda) Ltd. | Methods of administering anti-tnf.alpha. antibodies |
WO2003000282A1 (en) * | 2001-06-21 | 2003-01-03 | Genentech, Inc. | Sustained release formulation |
US20030113316A1 (en) | 2001-07-25 | 2003-06-19 | Kaisheva Elizabet A. | Stable lyophilized pharmaceutical formulation of IgG antibodies |
US6818613B2 (en) * | 2001-11-07 | 2004-11-16 | Ortho-Mcneil Pharmaceutical, Inc. | Aqueous sustained-release formulations of proteins |
PT1441589E (pt) * | 2001-11-08 | 2012-08-13 | Abbott Biotherapeutics Corp | Formulação farmacêutica líquida estável de anticorpos igg |
GB0202633D0 (en) | 2002-02-05 | 2002-03-20 | Delta Biotechnology Ltd | Stabilization of protein preparations |
EP3192528A1 (en) * | 2002-02-14 | 2017-07-19 | Chugai Seiyaku Kabushiki Kaisha | Formulation of anti-il6r antibody-containing solutions comprising a sugar as a stabilizer |
US20030161828A1 (en) * | 2002-02-19 | 2003-08-28 | Abbott Gmbh & Co. Kg | Use of TNF antagonists as drugs for the treatment of patients with an inflammatory reaction and without suffering from total organ failure |
AU2003219958B2 (en) * | 2002-02-27 | 2006-01-05 | Immunex Corporation | Polypeptide formulation |
US20040009172A1 (en) * | 2002-04-26 | 2004-01-15 | Steven Fischkoff | Use of anti-TNFalpha antibodies and another drug |
US20030206898A1 (en) * | 2002-04-26 | 2003-11-06 | Steven Fischkoff | Use of anti-TNFalpha antibodies and another drug |
NZ537687A (en) * | 2002-06-21 | 2008-04-30 | Biogen Idec Inc | Buffered formulations for concentrating antibodies and methods of use thereof |
US7601351B1 (en) | 2002-06-26 | 2009-10-13 | Human Genome Sciences, Inc. | Antibodies against protective antigen |
EP1539212A4 (en) | 2002-07-12 | 2007-05-02 | Medarex Inc | METHOD AND COMPOSITIONS FOR PREVENTING OXIDATIVE DEGRADATION OF PROTEINS |
US20090280065A1 (en) | 2006-04-10 | 2009-11-12 | Willian Mary K | Uses and Compositions for Treatment of Psoriasis |
EP2298810A3 (en) * | 2002-07-19 | 2011-08-03 | Abbott Biotechnology Ltd | Treatment of TNF alpha related disorders |
US20040033228A1 (en) * | 2002-08-16 | 2004-02-19 | Hans-Juergen Krause | Formulation of human antibodies for treating TNF-alpha associated disorders |
MY150740A (en) * | 2002-10-24 | 2014-02-28 | Abbvie Biotechnology Ltd | Low dose methods for treating disorders in which tnf? activity is detrimental |
UY28126A1 (es) | 2002-12-24 | 2004-06-30 | Alcon Inc | Uso de glucocorticoides selectivos para la superficie ocular en el tratamiento de la sequedad ocular |
JP4980048B2 (ja) * | 2003-02-28 | 2012-07-18 | アレス トレーディング ソシエテ アノニム | 腫瘍壊死因子結合タンパク質の液体製剤 |
DE602004003101T2 (de) | 2003-04-25 | 2007-02-15 | S.C. Johnson & Son, Inc., Racine | Am rand eines toilettenbeckens angebrachte vorrichtung zur abgabe von zwei flüssigkeiten |
CA2558135C (en) | 2004-03-18 | 2012-08-14 | R-Tech Ueno, Ltd. | Aqueous composition comprising thiazole derivative |
TW201705980A (zh) * | 2004-04-09 | 2017-02-16 | 艾伯維生物技術有限責任公司 | 用於治療TNFα相關失調症之多重可變劑量療法 |
US20060083741A1 (en) * | 2004-10-08 | 2006-04-20 | Hoffman Rebecca S | Treatment of respiratory syncytial virus (RSV) infection |
CA2903138A1 (en) * | 2005-05-16 | 2006-11-23 | Abbvie Biotechnology Ltd. | Use of tnfa inhibitor for treatment of erosive polyarthritis |
EP3673919A1 (en) | 2005-06-14 | 2020-07-01 | Amgen Inc. | Self-buffering protein formulations |
US20070041905A1 (en) | 2005-08-19 | 2007-02-22 | Hoffman Rebecca S | Method of treating depression using a TNF-alpha antibody |
EP1948235B1 (en) * | 2005-11-01 | 2013-08-28 | AbbVie Biotechnology Ltd | Methods for determining efficacy of adalimumab in subjects having ankylosing spondylitis using ctx-ii and mmp3 as biomarkers |
SG170837A1 (en) | 2006-04-05 | 2011-05-30 | Abbott Biotech Ltd | Antibody purification |
US20090317399A1 (en) * | 2006-04-10 | 2009-12-24 | Pollack Paul F | Uses and compositions for treatment of CROHN'S disease |
US9605064B2 (en) | 2006-04-10 | 2017-03-28 | Abbvie Biotechnology Ltd | Methods and compositions for treatment of skin disorders |
EP2012586A4 (en) * | 2006-04-10 | 2010-08-18 | Abbott Biotech Ltd | USES AND COMPOSITIONS FOR THE TREATMENT OF ANKYLOSANTE SPONDYLARTHRITIS |
US9399061B2 (en) * | 2006-04-10 | 2016-07-26 | Abbvie Biotechnology Ltd | Methods for determining efficacy of TNF-α inhibitors for treatment of rheumatoid arthritis |
US20080118496A1 (en) * | 2006-04-10 | 2008-05-22 | Medich John R | Uses and compositions for treatment of juvenile rheumatoid arthritis |
EP2007426A4 (en) * | 2006-04-10 | 2010-06-16 | Abbott Biotech Ltd | COMPOSITIONS FOR THE TREATMENT OF PSORIASTIC POLYARTHRITIS AND THEIR APPLICATIONS |
US20080131374A1 (en) * | 2006-04-19 | 2008-06-05 | Medich John R | Uses and compositions for treatment of rheumatoid arthritis |
US20100021451A1 (en) | 2006-06-08 | 2010-01-28 | Wong Robert L | Uses and compositions for treatment of ankylosing spondylitis |
US20080311043A1 (en) * | 2006-06-08 | 2008-12-18 | Hoffman Rebecca S | Uses and compositions for treatment of psoriatic arthritis |
EP2043711A4 (en) | 2006-06-30 | 2017-08-30 | AbbVie Biotechnology Ltd | Automatic injection device |
EP1882476B1 (de) | 2006-07-25 | 2008-11-19 | HERDEIS, Claus | Herstellung von antimikrobiellen Formulierungen unter Verwendung von 7-Oxa-2-thia 1,5-diazabicyclo[3.3.1]nonan-2,2-dion |
TW201516149A (zh) * | 2006-09-13 | 2015-05-01 | Abbvie Inc | 細胞培養改良 |
EP2684895A1 (en) | 2006-10-27 | 2014-01-15 | AbbVie Biotechnology Ltd | Crystalline anti-hTNFalpha antibodies |
US8092998B2 (en) * | 2007-05-31 | 2012-01-10 | Abbott Laboratories | Biomarkers predictive of the responsiveness to TNFα inhibitors in autoimmune disorders |
EP2152318A4 (en) * | 2007-06-01 | 2011-12-07 | Abbott Biotech Ltd | COMPOSITIONS AND USES FOR THE TREATMENT OF PSORIASIS AND CROHN'S DISEASE |
WO2008154543A2 (en) * | 2007-06-11 | 2008-12-18 | Abbott Biotechnology Ltd. | Methods for treating juvenile idiopathic arthritis |
CN101848733A (zh) * | 2007-07-13 | 2010-09-29 | 艾博特生物技术有限公司 | 用于肺部给予TNFα抑制剂的方法和组合物 |
WO2009020654A1 (en) | 2007-08-08 | 2009-02-12 | Abbott Laboratories | Compositions and methods for crystallizing antibodies |
CA2696210A1 (en) | 2007-08-28 | 2009-03-12 | Abbott Biotechnology Ltd. | Compositions and methods comprising binding proteins for adalimumab |
US8883146B2 (en) | 2007-11-30 | 2014-11-11 | Abbvie Inc. | Protein formulations and methods of making same |
NZ602498A (en) | 2007-11-30 | 2014-08-29 | Abbvie Inc | Protein formulations and methods of making same |
WO2009086550A1 (en) * | 2008-01-03 | 2009-07-09 | Abbott Laboratories | Predicting long-term efficacy of a compound in the treatment of psoriasis |
NZ600979A (en) * | 2008-01-15 | 2014-01-31 | Abbott Lab | Improved mammalian expression vectors and uses thereof |
NZ586828A (en) * | 2008-01-15 | 2012-12-21 | Abbott Gmbh & Co Kg | Powdered antibody compositions and methods of making same |
EP2271671A2 (en) | 2008-03-24 | 2011-01-12 | Abbott Biotechnology Ltd. | Tnf-alpha inhibitors for treating bone loss |
MX2011011541A (es) | 2009-04-29 | 2012-02-28 | Abbott Biotech Ltd | Dispositivo de inyeccion automatico. |
NZ595694A (en) * | 2009-05-04 | 2013-09-27 | Abbvie Biotechnology Ltd | Stable high protein concentration formulations of human anti-tnf-alpha-antibodies |
TWI603739B (zh) | 2010-11-11 | 2017-11-01 | 艾伯維生物技術有限責任公司 | 具有增進高濃度之抗-TNFα抗體之液體調配物 |
MX363700B (es) | 2012-03-07 | 2019-03-29 | Cadila Healthcare Ltd | Formulaciones farmaceuticas de anticuerpos tnf-alfa. |
-
2002
- 2002-08-16 US US10/222,140 patent/US20040033228A1/en not_active Abandoned
-
2003
- 2003-08-08 MY MYPI2012001176A patent/MY163027A/en unknown
- 2003-08-08 MY MYPI20033010A patent/MY153718A/en unknown
- 2003-08-08 MY MYPI20070749A patent/MY162068A/en unknown
- 2003-08-12 TW TW092122123A patent/TWI331532B/zh not_active IP Right Cessation
- 2003-08-15 CN CN201010613919.XA patent/CN102078608B/zh not_active Expired - Lifetime
- 2003-08-15 CA CA2882931A patent/CA2882931C/en not_active Expired - Lifetime
- 2003-08-15 PL PL398596A patent/PL218221B1/pl unknown
- 2003-08-15 CA CA2882934A patent/CA2882934C/en not_active Expired - Lifetime
- 2003-08-15 KR KR1020117007142A patent/KR101273568B1/ko active IP Right Grant
- 2003-08-15 CA CA2854798A patent/CA2854798A1/en not_active Abandoned
- 2003-08-15 CN CN201010613946.7A patent/CN102049045B/zh not_active Withdrawn - After Issue
- 2003-08-15 ES ES03748439T patent/ES2387616T3/es not_active Expired - Lifetime
- 2003-08-15 PL PL406852A patent/PL218834B1/pl unknown
- 2003-08-15 CA CA2872091A patent/CA2872091A1/en not_active Abandoned
- 2003-08-15 CA CA2872088A patent/CA2872088A1/en not_active Abandoned
- 2003-08-15 BR BR0313492-0A patent/BR0313492A/pt not_active Application Discontinuation
- 2003-08-15 CA CA2882907A patent/CA2882907C/en not_active Expired - Lifetime
- 2003-08-15 ES ES10182610.5T patent/ES2636692T3/es not_active Expired - Lifetime
- 2003-08-15 SI SI200332176T patent/SI1528933T1/sl unknown
- 2003-08-15 EP EP10182625A patent/EP2363145A1/en not_active Withdrawn
- 2003-08-15 KR KR1020127026957A patent/KR101367743B1/ko active IP Right Grant
- 2003-08-15 CA CA2494756A patent/CA2494756C/en not_active Expired - Lifetime
- 2003-08-15 DK DK03748439.1T patent/DK1528933T3/da active
- 2003-08-15 EP EP03748439A patent/EP1528933B1/en not_active Revoked
- 2003-08-15 CN CN038242729A patent/CN1688339B/zh not_active Expired - Lifetime
- 2003-08-15 PT PT101826105T patent/PT2359856T/pt unknown
- 2003-08-15 EP EP10182598A patent/EP2363144A1/en not_active Withdrawn
- 2003-08-15 US US10/525,292 patent/US8216583B2/en active Active
- 2003-08-15 AR AR20030102982A patent/AR040881A1/es not_active Application Discontinuation
- 2003-08-15 AT AT03748439T patent/ATE555809T1/de active
- 2003-08-15 PT PT03748439T patent/PT1528933E/pt unknown
- 2003-08-15 CN CN200910253163.XA patent/CN101721702B/zh not_active Expired - Lifetime
- 2003-08-15 MX MXPA05001841A patent/MXPA05001841A/es active IP Right Grant
- 2003-08-15 CA CA2872089A patent/CA2872089C/en not_active Expired - Lifetime
- 2003-08-15 WO PCT/IB2003/004502 patent/WO2004016286A2/en active Application Filing
- 2003-08-15 SI SI200332534T patent/SI2359856T1/sl unknown
- 2003-08-15 KR KR1020137022247A patent/KR101529583B1/ko active IP Right Grant
- 2003-08-15 DK DK10182610.5T patent/DK2359856T3/en active
- 2003-08-15 EP EP10182610.5A patent/EP2359856B1/en not_active Revoked
- 2003-08-15 NZ NZ538030A patent/NZ538030A/en not_active IP Right Cessation
- 2003-08-15 PL PL375272A patent/PL212934B1/pl unknown
- 2003-08-15 EP EP20100182619 patent/EP2361637A1/en not_active Withdrawn
- 2003-08-15 UY UY27940A patent/UY27940A1/es not_active Application Discontinuation
- 2003-08-15 CA CA2882905A patent/CA2882905C/en not_active Expired - Lifetime
- 2003-08-15 AU AU2003267744A patent/AU2003267744C1/en not_active Expired
- 2003-08-15 PE PE2003000831A patent/PE20040994A1/es not_active Application Discontinuation
- 2003-08-15 JP JP2004528780A patent/JP4925582B2/ja not_active Expired - Lifetime
- 2003-08-15 KR KR1020057002604A patent/KR20050067140A/ko not_active Application Discontinuation
-
2005
- 2005-02-03 ZA ZA200501032A patent/ZA200501032B/en unknown
- 2005-02-10 IL IL166809A patent/IL166809A/en active IP Right Grant
- 2005-09-15 HK HK05108068.5A patent/HK1074008A1/xx not_active IP Right Cessation
-
2010
- 2010-06-08 CL CL2010000603A patent/CL2010000603A1/es unknown
- 2010-07-14 AR ARP100102557A patent/AR077412A2/es unknown
- 2010-07-15 IL IL207028A patent/IL207028A/en active IP Right Grant
-
2011
- 2011-09-20 JP JP2011204759A patent/JP5608619B2/ja not_active Expired - Lifetime
-
2012
- 2012-05-15 US US13/471,820 patent/US8932591B2/en not_active Expired - Lifetime
- 2012-07-17 CY CY20121100631T patent/CY1113353T1/el unknown
-
2013
- 2013-11-14 JP JP2013235924A patent/JP2014074034A/ja active Pending
- 2013-11-27 US US14/091,938 patent/US8795670B2/en not_active Expired - Lifetime
- 2013-11-27 US US14/091,661 patent/US8802100B2/en not_active Expired - Lifetime
- 2013-11-27 US US14/091,888 patent/US8802101B2/en not_active Expired - Lifetime
-
2014
- 2014-01-03 US US14/147,287 patent/US8802102B2/en not_active Expired - Lifetime
- 2014-07-02 US US14/322,581 patent/US8911741B2/en not_active Expired - Lifetime
- 2014-07-02 US US14/322,565 patent/US8940305B2/en not_active Expired - Lifetime
- 2014-08-06 US US14/453,461 patent/US8916157B2/en not_active Expired - Lifetime
- 2014-08-06 US US14/453,490 patent/US8916158B2/en not_active Expired - Lifetime
- 2014-12-02 US US14/558,182 patent/US9114166B2/en not_active Expired - Lifetime
-
2015
- 2015-05-15 JP JP2015099796A patent/JP2015199741A/ja not_active Withdrawn
- 2015-07-14 US US14/799,211 patent/US9220781B2/en not_active Expired - Lifetime
- 2015-08-14 US US14/826,367 patent/US9272041B2/en not_active Expired - Fee Related
- 2015-08-14 US US14/826,377 patent/US9295725B2/en not_active Expired - Fee Related
- 2015-08-14 US US14/826,357 patent/US9327032B2/en not_active Expired - Fee Related
- 2015-08-14 US US14/826,383 patent/US9272042B2/en not_active Expired - Fee Related
- 2015-08-14 US US14/826,393 patent/US9289497B2/en not_active Expired - Fee Related
- 2015-10-15 US US14/884,279 patent/US9302011B2/en not_active Expired - Fee Related
-
2016
- 2016-04-11 US US15/095,393 patent/US9950066B2/en not_active Expired - Lifetime
-
2017
- 2017-01-27 US US15/418,460 patent/US9750808B2/en not_active Expired - Lifetime
- 2017-01-27 US US15/418,469 patent/US9738714B2/en not_active Expired - Lifetime
- 2017-01-27 US US15/418,465 patent/US9732152B2/en not_active Expired - Lifetime
- 2017-04-05 JP JP2017074982A patent/JP2017165736A/ja active Pending
- 2017-05-19 CY CY20171100527T patent/CY1118991T1/el unknown
-
2018
- 2018-03-12 US US15/918,663 patent/US20190054171A1/en not_active Abandoned
- 2018-08-07 US US16/057,217 patent/US20180339046A1/en not_active Abandoned
-
2020
- 2020-12-18 US US17/126,500 patent/US20210113694A1/en not_active Abandoned
-
2021
- 2021-09-10 US US17/472,004 patent/US20220241415A1/en active Pending
Cited By (295)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20070249813A1 (en) * | 1996-02-09 | 2007-10-25 | Salfeld Jochen G | Human antibodies that bind human TNFa |
US8206714B2 (en) | 1996-02-09 | 2012-06-26 | Abbott Biotechnology Ltd. | Methods for treating rheumatoid arthritis using human antibodies that bind human TNFa |
US8753633B2 (en) | 1996-02-09 | 2014-06-17 | Abbvie Biotechnology Ltd. | Human antibodies that bind human TNFα |
US7588761B2 (en) | 1996-02-09 | 2009-09-15 | Abbott Biotechnology Ltd. | Human antibodies that bind human TNFα |
US20100016557A1 (en) * | 1996-02-09 | 2010-01-21 | Abbott Biotechnology Ltd. | HUMAN ANTIBODIES THAT BIND HUMAN TNFalpha |
US20100040604A1 (en) * | 1996-02-09 | 2010-02-18 | Salfeld Jochen G | HUMAN ANTIBODIES THAT BIND HUMAN TNFalpha |
US8414894B2 (en) | 1996-02-09 | 2013-04-09 | Abbott Biotechnology Ltd. | Human antibodies that bind human TNFα and methods of using same |
US8197813B2 (en) | 1996-02-09 | 2012-06-12 | Abbott Biotechnology Ltd. | Human antibodies that bind human TNFα |
US7541031B2 (en) | 1996-02-09 | 2009-06-02 | Abbott Biotechnology Ltd. | Methods for treating rheumatoid arthritis using human antibodies that bind human TNFα |
US8372400B2 (en) | 1996-02-09 | 2013-02-12 | Abbott Biotechnology Ltd. | Methods of treating disorders using human antibodies that bind human TNFα |
US8372401B2 (en) | 1996-02-09 | 2013-02-12 | Abbott Biotechnology Ltd. | Human antibodies that bind human TNFα |
US20090155205A1 (en) * | 1996-02-09 | 2009-06-18 | Salfeld Jochen G | HUMAN ANTIBODIES THAT BIND HUMAN TNFa |
US8974790B2 (en) | 2001-06-08 | 2015-03-10 | Abbvie Biotechnology Ltd. | Methods of administering anti-TNFα antibodies |
US8992926B2 (en) | 2001-06-08 | 2015-03-31 | Abbvie Biotechnology Ltd. | Methods of administering anti-TNFα antibodies |
US9546212B2 (en) | 2001-06-08 | 2017-01-17 | Abbvie Biotechnology Ltd. | Methods of administering anti-TNFα antibodies |
US20030235585A1 (en) * | 2001-06-08 | 2003-12-25 | Fischkoff Steven A. | Methods of administering anti-TNFalpha antibodies |
US9017680B2 (en) | 2001-06-08 | 2015-04-28 | Abbvie Biotechnology Ltd. | Methods of administering anti-TNFα antibodies |
US8889135B2 (en) | 2001-06-08 | 2014-11-18 | Abbvie Biotechnology Ltd. | Methods of administering anti-TNFα antibodies |
US8911737B2 (en) | 2001-06-08 | 2014-12-16 | Abbvie Biotechnology Ltd. | Methods of administering anti-TNFα antibodies |
US9073987B2 (en) | 2001-06-08 | 2015-07-07 | Abbvie Biotechnology Ltd. | Methods of administering anti-TNFα antibodies |
US10322176B2 (en) | 2002-03-01 | 2019-06-18 | Immunomedics, Inc. | Subcutaneous administration of anti-CD74 antibody for systemic lupus erythematosus |
US20040009172A1 (en) * | 2002-04-26 | 2004-01-15 | Steven Fischkoff | Use of anti-TNFalpha antibodies and another drug |
US20070202104A1 (en) * | 2002-07-19 | 2007-08-30 | Abbott Laboratories S.A. | Treatment of spondyloarthropathies using TNFalpha inhibitors |
US9090689B1 (en) | 2002-07-19 | 2015-07-28 | Abbvie Biotechnology Ltd. | Use of TNFα inhibitor for treatment of psoriasis |
US9085620B1 (en) | 2002-07-19 | 2015-07-21 | Abbvie Biotechnology Ltd. | Use of TNFα inhibitor for treatment of psoriatic arthritis |
US20040126372A1 (en) * | 2002-07-19 | 2004-07-01 | Abbott Biotechnology Ltd. | Treatment of TNFalpha related disorders |
US8906373B2 (en) | 2002-07-19 | 2014-12-09 | Abbvie Biotechnology Ltd. | Use of TNF-alpha inhibitor for treatment of psoriasis |
US9220781B2 (en) | 2002-08-16 | 2015-12-29 | Abbvie Biotechnology Ltd | Formulation of human antibodies for treating TNF-alpha associated disorders |
US9302011B2 (en) | 2002-08-16 | 2016-04-05 | Abbvie Biotechnology Ltd | Formulation of human antibodies for treating TNF-α associated disorders |
US20060153846A1 (en) * | 2002-08-16 | 2006-07-13 | Hans-Juergen Krause | Formulation of human antibodies for treating tnf-alpha associated disorders |
US8940305B2 (en) | 2002-08-16 | 2015-01-27 | Abbvie Biotechnology Ltd. | Formulation of human antibodies for treating TNF-α associated disorders |
US8932591B2 (en) | 2002-08-16 | 2015-01-13 | Abbvie Biotechnology Ltd. | Formulation of human antibodies for treating TNF-α associated disorders |
US8916158B2 (en) | 2002-08-16 | 2014-12-23 | Abbvie Biotechnology Ltd. | Formulation of human antibodies for treating TNF-α associated disorders |
US8916157B2 (en) | 2002-08-16 | 2014-12-23 | Abbvie Biotechnology Ltd. | Formulation of human antibodies for treating TNF-α associated disorders |
US8911741B2 (en) | 2002-08-16 | 2014-12-16 | Abbvie Biotechnology Ltd. | Formulation of human antibodies for treating TNF-alpha associated disorders |
US9114166B2 (en) | 2002-08-16 | 2015-08-25 | Abbvie Biotechnology Ltd. | Formulation of human antibodies for treating TNF-α associated disorders |
US8802100B2 (en) | 2002-08-16 | 2014-08-12 | Abbvie Biotechnology Ltd. | Formulation of human antibodies for treating TNF-alpha associated disorders |
US8802101B2 (en) | 2002-08-16 | 2014-08-12 | Abbvie Biotechnology Ltd. | Formulation of human antibodies for treating TNF-α associated disorders |
US8802102B2 (en) | 2002-08-16 | 2014-08-12 | Abbvie Biotechnology Ltd. | Formulation of human antibodies for treating TNF-α associated disorders |
US8795670B2 (en) | 2002-08-16 | 2014-08-05 | Abbvie Biotechnology Ltd. | Formulation of human antibodies for treating TNF-alpha associated disorders |
US9272041B2 (en) | 2002-08-16 | 2016-03-01 | Abbvie Biotechnology Ltd | Formulation of human antibodies for treating TNF-alpha associated disorders |
US9272042B2 (en) | 2002-08-16 | 2016-03-01 | Abbvie Biotechnology Ltd | Formulation of human antibodies for treating TNF-alpha associated disorders |
US9289497B2 (en) | 2002-08-16 | 2016-03-22 | Abbvie Biotechnology Ltd | Formulation of human antibodies for treating TNF-alpha associated disorders |
US9295725B2 (en) | 2002-08-16 | 2016-03-29 | Abbvie Biotechnology Ltd | Formulation of human antibodies for treating TNF-alpha associated disorders |
US9327032B2 (en) | 2002-08-16 | 2016-05-03 | Abbvie Biotechnology Ltd | Formulation of human antibodies for treating TNF-alpha associated disorders |
US8216583B2 (en) | 2002-08-16 | 2012-07-10 | Abbott Biotechnology, Ltd. | Formulation of human antibodies for treating TNF-α associated disorders |
US9732152B2 (en) | 2002-08-16 | 2017-08-15 | Abbvie Biotechnology Ltd | Formulation of human antibodies for treating TNF-alpha associated disorders |
US9950066B2 (en) | 2002-08-16 | 2018-04-24 | Abbvie Biotechnology Ltd | Formulation of human antibodies for treating TNF-alpha associated disorders |
US9738714B2 (en) | 2002-08-16 | 2017-08-22 | Abbvie Biotechnology Ltd | Formulation of human antibodies for treating TNF-alpha associated disorders |
US9750808B2 (en) | 2002-08-16 | 2017-09-05 | Abbvie Biotechnology Ltd. | Formulation of human antibodies for treating TNF-alpha associated disorders |
US20040166111A1 (en) * | 2002-10-24 | 2004-08-26 | Zehra Kaymakcalan | Low dose methods for treating disorders in which TNFalpha activity is detrimental |
US8846046B2 (en) | 2002-10-24 | 2014-09-30 | Abbvie Biotechnology Ltd. | Low dose methods for treating disorders in which TNFα activity is detrimental |
US20180194843A1 (en) * | 2003-02-10 | 2018-07-12 | Biogen Ma Inc. | Immunoglobulin formulation and method of preparation thereof |
US10954303B2 (en) * | 2003-02-10 | 2021-03-23 | Biogen Ma Inc. | Immunoglobulin formulation and method of preparation thereof |
WO2005063291A1 (ja) * | 2003-12-25 | 2005-07-14 | Kirin Beer Kabushiki Kaisha | 抗体を含有する安定な水性医薬製剤 |
US20070184050A1 (en) * | 2003-12-25 | 2007-08-09 | Kirin Beer Kabushiki Kaisha | Stable water-based medicinal preparation containing antibody |
US9512216B2 (en) | 2004-04-09 | 2016-12-06 | Abbvie Biotechnology Ltd. | Use of TNFα inhibitor |
US9187559B2 (en) | 2004-04-09 | 2015-11-17 | Abbvie Biotechnology Ltd | Multiple-variable dose regimen for treating idiopathic inflammatory bowel disease |
US8986693B1 (en) | 2004-04-09 | 2015-03-24 | Abbvie Biotechnology Ltd. | Use of TNFα inhibitor for treatment of psoriasis |
US20090304682A1 (en) * | 2004-04-09 | 2009-12-10 | Hoffman Rebecca S | Multiple-variable dose regimen for treating TNFa-related disorders |
US8889136B2 (en) | 2004-04-09 | 2014-11-18 | Abbvie Biotechnology Ltd. | Multiple-variable dose regimen for treating TNFα-related disorders |
US20060009385A1 (en) * | 2004-04-09 | 2006-01-12 | Abbott Biotechnology Ltd. | Multiple-variable dose regimen for treating TNFalpha-related disorders |
US9061005B2 (en) | 2004-04-09 | 2015-06-23 | Abbvie Biotechnology Ltd | Multiple-variable dose regimen for treating idiopathic inflammatory bowel disease |
US8961973B2 (en) | 2004-04-09 | 2015-02-24 | Abbvie Biotechnology Ltd. | Multiple-variable dose regimen for treating TNFα-related disorders |
US8961974B2 (en) | 2004-04-09 | 2015-02-24 | Abbvie Biotechnology Ltd. | Multiple-variable dose regimen for treating TNFα-related disorders |
US9499615B2 (en) | 2004-04-09 | 2016-11-22 | Abbvie Biotechnology Ltd | Multiple-variable dose regimen for treating idiopathic inflammatory bowel disease |
US8668670B2 (en) | 2004-06-23 | 2014-03-11 | Abbvie Biotechnology Ltd | Automatic injection devices |
US9017287B2 (en) | 2004-06-23 | 2015-04-28 | Abbvie Biotechnology Ltd | Automatic injection devices |
US8162887B2 (en) | 2004-06-23 | 2012-04-24 | Abbott Biotechnology Ltd. | Automatic injection devices |
US20060083741A1 (en) * | 2004-10-08 | 2006-04-20 | Hoffman Rebecca S | Treatment of respiratory syncytial virus (RSV) infection |
US11180559B2 (en) | 2005-03-03 | 2021-11-23 | Immunomedics, Inc. | Subcutaneous anti-HLA-DR monoclonal antibody for treatment of hematologic malignancies |
US9493569B2 (en) | 2005-03-31 | 2016-11-15 | Chugai Seiyaku Kabushiki Kaisha | Structural isomers of sc(Fv)2 |
US8715664B2 (en) | 2005-05-16 | 2014-05-06 | Abbvie Biotechnology Ltd. | Use of human TNFα antibodies for treatment of erosive polyarthritis |
US8808700B1 (en) | 2005-05-16 | 2014-08-19 | Abbvie Biotechnology Ltd. | Use of TNF alpha inhibitor for treatment of erosive polyarthritis |
US20070071747A1 (en) * | 2005-05-16 | 2007-03-29 | Hoffman Rebecca S | Use of TNFalpha inhibitor for treatment of erosive polyarthritis |
US9067992B2 (en) | 2005-05-16 | 2015-06-30 | Abbvie Biotechnology Ltd. | Use of TNFα inhibitor for treatment of psoriatic arthritis |
US20060269543A1 (en) * | 2005-05-19 | 2006-11-30 | Amgen Inc. | Compositions and methods for increasing the stability of antibodies |
US8858935B2 (en) | 2005-05-19 | 2014-10-14 | Amgen Inc. | Compositions and methods for increasing the stability of antibodies |
US20090214535A1 (en) * | 2005-06-10 | 2009-08-27 | Chugai Seiyaku Kabushiki Kaisha | Pharmaceutical Compositions Containing sc(Fv)2 |
US9777066B2 (en) | 2005-06-10 | 2017-10-03 | Chugai Seiyaku Kabushiki Kaisha | Pharmaceutical compositions containing sc(Fv)2 |
US9241994B2 (en) * | 2005-06-10 | 2016-01-26 | Chugai Seiyaku Kabushiki Kaisha | Pharmaceutical compositions containing sc(Fv)2 |
US11607451B2 (en) | 2005-06-14 | 2023-03-21 | Amgen Inc. | Self-buffering antibody formulations |
US20070081996A1 (en) * | 2005-08-19 | 2007-04-12 | Hoffman Rebecca S | Method of treating depression using a TNFalpha antibody |
US20070041905A1 (en) * | 2005-08-19 | 2007-02-22 | Hoffman Rebecca S | Method of treating depression using a TNF-alpha antibody |
US7919264B2 (en) | 2005-11-01 | 2011-04-05 | Abbott Biotechnology Ltd. | Methods and compositions for determining the efficacy of a treatment for ankylosing spondylitis using biomarkers |
US20070172897A1 (en) * | 2005-11-01 | 2007-07-26 | Maksymowych Walter P | Methods and compositions for diagnosing ankylosing spondylitis using biomarkers |
US9086418B2 (en) | 2005-11-01 | 2015-07-21 | Abbvie Biotechnology Ltd. | Methods and compositions for diagnosing ankylosing spondylitis using biomarkers |
WO2007072380A2 (en) * | 2005-12-19 | 2007-06-28 | Koninklijke Philips Electronics N.V. | Method of making dried particles |
US20080257021A1 (en) * | 2005-12-19 | 2008-10-23 | Koninklijke Philips Electronics, N.V. | Method of Making Dried Particles |
WO2007072380A3 (en) * | 2005-12-19 | 2007-10-11 | Koninkl Philips Electronics Nv | Method of making dried particles |
EP1798504A1 (en) * | 2005-12-19 | 2007-06-20 | Koninklijke Philips Electronics N.V. | Method of making dried particles |
US8906372B2 (en) | 2006-04-05 | 2014-12-09 | Abbvie Biotechnology Ltd. | Purified antibody composition |
US8883156B2 (en) | 2006-04-05 | 2014-11-11 | Abbvie Biotechnology Ltd. | Purified antibody composition |
US9273132B2 (en) | 2006-04-05 | 2016-03-01 | Abbvie Biotechnology Ltd | Purified antibody composition |
US20110002935A1 (en) * | 2006-04-05 | 2011-01-06 | Min Wan | Antibody purification |
US9913902B2 (en) | 2006-04-05 | 2018-03-13 | Abbvie Biotechnology Ltd. | Purified antibody composition |
US20070292442A1 (en) * | 2006-04-05 | 2007-12-20 | Min Wan | Antibody purification |
US8231876B2 (en) | 2006-04-05 | 2012-07-31 | Abbott Biotechnology Ltd. | Purified antibody composition |
US11083792B2 (en) | 2006-04-05 | 2021-08-10 | Abbvie Biotechnology Ltd | Purified antibody composition |
US9096666B2 (en) | 2006-04-05 | 2015-08-04 | Abbvie Biotechnology Ltd | Purified antibody composition |
US9102723B2 (en) | 2006-04-05 | 2015-08-11 | Abbvie Biotechnology Ltd | Purified antibody composition |
US8916153B2 (en) | 2006-04-05 | 2014-12-23 | Abbvie Biotechnology Ltd. | Purified antibody composition |
US7863426B2 (en) | 2006-04-05 | 2011-01-04 | Abbott Biotechnology Ltd. | Antibody purification |
US9328165B2 (en) | 2006-04-05 | 2016-05-03 | Abbvie Biotechnology Ltd. | Purified antibody composition |
US8895009B2 (en) | 2006-04-05 | 2014-11-25 | Abbvie Biotechnology Ltd. | Purified antibody composition |
EP2703010A2 (en) | 2006-04-10 | 2014-03-05 | Abbott Biotechnology Ltd. | Uses and compositions for treatment of rheumatoid arthritis |
WO2008063213A2 (en) | 2006-04-10 | 2008-05-29 | Abbott Biotechnology Ltd. | Uses and compositions for treatment of psoriatic arthritis |
EP2666472A2 (en) | 2006-04-10 | 2013-11-27 | Abbott Biotechnology Ltd | Uses and compositions for treatment of psoriatic arthritis |
US20090317399A1 (en) * | 2006-04-10 | 2009-12-24 | Pollack Paul F | Uses and compositions for treatment of CROHN'S disease |
EP2666480A2 (en) | 2006-04-10 | 2013-11-27 | Abbott Biotechnology Ltd | Uses and compositions for treatment of Crohn's desease |
US20110171227A1 (en) * | 2006-04-10 | 2011-07-14 | Okun Martin M | Methods and compositions for treatment of skin disorders |
US20080166348A1 (en) * | 2006-04-10 | 2008-07-10 | Hartmut Kupper | Uses and compositions for treatment of rheumatoid arthritis |
EP2666478A2 (en) | 2006-04-10 | 2013-11-27 | Abbott Biotechnology Ltd | Uses and compositions for treatment of psoriasis |
EP2666479A2 (en) | 2006-04-10 | 2013-11-27 | Abbott Biotechnology Ltd | Uses and compositions for treatment of juvenile rheumatoid arthritis |
EP2708242A2 (en) | 2006-04-10 | 2014-03-19 | Abbott Biotechnology Ltd | Uses and compositions for treatment of ankylosing spondylitis |
US9624295B2 (en) | 2006-04-10 | 2017-04-18 | Abbvie Biotechnology Ltd. | Uses and compositions for treatment of psoriatic arthritis |
US9605064B2 (en) | 2006-04-10 | 2017-03-28 | Abbvie Biotechnology Ltd | Methods and compositions for treatment of skin disorders |
US20080118496A1 (en) * | 2006-04-10 | 2008-05-22 | Medich John R | Uses and compositions for treatment of juvenile rheumatoid arthritis |
US9399061B2 (en) | 2006-04-10 | 2016-07-26 | Abbvie Biotechnology Ltd | Methods for determining efficacy of TNF-α inhibitors for treatment of rheumatoid arthritis |
US9279015B2 (en) | 2006-04-10 | 2016-03-08 | Robert L. Wong | Methods for treatment of ankylosing spondylitis using TNF alpha antibodies |
US20090280065A1 (en) * | 2006-04-10 | 2009-11-12 | Willian Mary K | Uses and Compositions for Treatment of Psoriasis |
US20080131374A1 (en) * | 2006-04-19 | 2008-06-05 | Medich John R | Uses and compositions for treatment of rheumatoid arthritis |
US20080311043A1 (en) * | 2006-06-08 | 2008-12-18 | Hoffman Rebecca S | Uses and compositions for treatment of psoriatic arthritis |
US8926975B2 (en) | 2006-06-08 | 2015-01-06 | Abbvie Biotechnology Ltd | Method of treating ankylosing spondylitis |
US20100021451A1 (en) * | 2006-06-08 | 2010-01-28 | Wong Robert L | Uses and compositions for treatment of ankylosing spondylitis |
US20100160894A1 (en) * | 2006-06-30 | 2010-06-24 | Julian Joseph F | Automatic injection device |
US8679061B2 (en) * | 2006-06-30 | 2014-03-25 | Abbvie Biotechnology Ltd | Automatic injection device |
US9486584B2 (en) | 2006-06-30 | 2016-11-08 | Abbvie Biotechnology Ltd. | Automatic injection device |
US20080112953A1 (en) * | 2006-10-06 | 2008-05-15 | Amgen Inc. | Stable formulations |
US8241632B2 (en) | 2006-10-20 | 2012-08-14 | Amgen Inc. | Stable polypeptide formulations |
US20080124326A1 (en) * | 2006-10-20 | 2008-05-29 | Amgen Inc. | Stable polypeptide formulations |
US20100158908A1 (en) * | 2006-10-20 | 2010-06-24 | Amgen Inc. | Stable Polypeptide Formulations |
US7705132B2 (en) | 2006-10-20 | 2010-04-27 | Amgen Inc. | Stable polypeptide formulations |
US8436149B2 (en) | 2006-10-27 | 2013-05-07 | Abbvie Biotechnology Ltd | Crystalline anti-hTNFalpha antibodies |
US8772458B2 (en) | 2006-10-27 | 2014-07-08 | Abbvie Biotechnology Ltd | Crystalline anti-hTNFalpha antibodies |
US20100034823A1 (en) * | 2006-10-27 | 2010-02-11 | Borhani David W | Crystalline anti-hTNFalpha antibodies |
US8034906B2 (en) | 2006-10-27 | 2011-10-11 | Abbott Biotechnology Ltd. | Crystalline anti-hTNFalpha antibodies |
US8092998B2 (en) | 2007-05-31 | 2012-01-10 | Abbott Laboratories | Biomarkers predictive of the responsiveness to TNFα inhibitors in autoimmune disorders |
US20090017472A1 (en) * | 2007-05-31 | 2009-01-15 | Bruno Stuhlmuller | BIOMARKERS PREDICTIVE OF THE RESPONSIVENESS TO TNFalpha INHIBITORS IN AUTOIMMUNE DISORDERS |
US9669093B2 (en) | 2007-06-11 | 2017-06-06 | Abbvie Biotechnology Ltd | Methods for treating juvenile idiopathic arthritis |
WO2008154543A2 (en) | 2007-06-11 | 2008-12-18 | Abbott Biotechnology Ltd. | Methods for treating juvenile idiopathic arthritis |
US8999337B2 (en) | 2007-06-11 | 2015-04-07 | Abbvie Biotechnology Ltd. | Methods for treating juvenile idiopathic arthritis by inhibition of TNFα |
US9284370B1 (en) | 2007-06-11 | 2016-03-15 | Abbvie Biotechnology Ltd. | Methods for treating juvenile idiopathic arthritis |
US20090258018A1 (en) * | 2007-06-11 | 2009-10-15 | Medich John R | Methods for treating juvenile idiopathic arthritis |
US20090110679A1 (en) * | 2007-07-13 | 2009-04-30 | Luk-Chiu Li | Methods and compositions for pulmonary administration of a TNFa inhibitor |
US8753839B2 (en) | 2007-08-08 | 2014-06-17 | Abbvie Inc. | Compositions and methods for crystallizing antibodies |
RU2659431C2 (ru) * | 2007-11-30 | 2018-07-02 | Эббви Байотекнолоджи Лтд. | Белковые композиции и способы их получения |
US11191834B2 (en) | 2007-11-30 | 2021-12-07 | Abbvie Biotechnology Ltd | Protein formulations and methods of making same |
EP2231175A4 (en) * | 2007-11-30 | 2014-07-16 | Abbvie Inc | PROTEIN FORMULATIONS AND MANUFACTURING METHOD |
US8883146B2 (en) | 2007-11-30 | 2014-11-11 | Abbvie Inc. | Protein formulations and methods of making same |
EP3189831A1 (en) * | 2007-11-30 | 2017-07-12 | AbbVie Biotechnology Ltd | Protein formulations and methods of making same |
US11167030B2 (en) | 2007-11-30 | 2021-11-09 | Abbvie Biotechnology Ltd | Protein formulations and methods of making same |
US8420081B2 (en) | 2007-11-30 | 2013-04-16 | Abbvie, Inc. | Antibody formulations and methods of making same |
US9085619B2 (en) | 2007-11-30 | 2015-07-21 | Abbvie Biotechnology Ltd. | Anti-TNF antibody formulations |
EP2231175A2 (en) | 2007-11-30 | 2010-09-29 | Abbott Laboratories | Protein formulations and methods of making same |
RU2470628C2 (ru) * | 2007-12-28 | 2012-12-27 | Биоинвент Интернешнл Аб | Состав |
US20090271164A1 (en) * | 2008-01-03 | 2009-10-29 | Peng Joanna Z | Predicting long-term efficacy of a compound in the treatment of psoriasis |
US9610301B2 (en) | 2008-01-15 | 2017-04-04 | Abbvie Deutschland Gmbh & Co Kg | Powdered protein compositions and methods of making same |
US8722860B2 (en) | 2009-04-16 | 2014-05-13 | Abbvie Biotherapeutics Inc. | Anti-TNF-α antibodies and their uses |
US20100266613A1 (en) * | 2009-04-16 | 2010-10-21 | Harding Fiona A | Anti-tnf-alpha antibodies and their uses |
EP2918602A1 (en) | 2009-04-16 | 2015-09-16 | AbbVie Biotherapeutics Inc. | Anti-TNF-alpha antibodies and their uses |
US8636704B2 (en) | 2009-04-29 | 2014-01-28 | Abbvie Biotechnology Ltd | Automatic injection device |
US20110054414A1 (en) * | 2009-04-29 | 2011-03-03 | Abbott Biotechnology Ltd. | Automatic Injection Device |
US20100278822A1 (en) * | 2009-05-04 | 2010-11-04 | Abbott Biotechnology, Ltd. | Stable high protein concentration formulations of human anti-tnf-alpha-antibodies |
US9944714B2 (en) | 2009-09-30 | 2018-04-17 | Tracon Pharmaceuticals, Inc. | Endoglin antibodies |
US9518122B2 (en) | 2009-09-30 | 2016-12-13 | Tracon Pharmaceuticals, Inc. | Endoglin antibodies |
US20110178500A1 (en) * | 2009-12-15 | 2011-07-21 | Shang Sherwin S | Firing button for automatic injection device |
US8758301B2 (en) | 2009-12-15 | 2014-06-24 | Abbvie Biotechnology Ltd | Firing button for automatic injection device |
US20110150891A1 (en) * | 2009-12-16 | 2011-06-23 | Philip Bosch | Methods of Treating Interstitial Cystitis |
WO2011075578A1 (en) | 2009-12-16 | 2011-06-23 | Philip Bosch | Methods of treating interstitial cystitis |
EP3360596A1 (en) | 2010-04-21 | 2018-08-15 | AbbVie Biotechnology Ltd. | Wearable automatic injection device for controlled delivery of therapeutic agents |
US9334320B2 (en) | 2010-06-03 | 2016-05-10 | Abbvie Biotechnology Ltd. | Methods of treating moderate to severe hidradenitis suppurativa with anti-TNFalpha antibody |
WO2011153477A2 (en) | 2010-06-03 | 2011-12-08 | Abbott Biotechnology Ltd. | Uses and compositions for treatment of hidradenitis suppurativa (hs) |
US8747854B2 (en) | 2010-06-03 | 2014-06-10 | Abbvie Biotechnology Ltd. | Methods of treating moderate to severe hidradenitis suppurativa with anti-TNF-alpha antibodies |
US8821865B2 (en) | 2010-11-11 | 2014-09-02 | Abbvie Biotechnology Ltd. | High concentration anti-TNFα antibody liquid formulations |
US9480743B2 (en) | 2010-12-28 | 2016-11-01 | Hexal Ag | Pharmaceutical formulation comprising a biopharmaceutical drug |
EP2658575B1 (en) * | 2010-12-28 | 2017-11-15 | Hexal AG | Pharmaceutical formulation comprising a biopharmaceutical drug |
US11565048B2 (en) | 2011-01-24 | 2023-01-31 | Abbvie Biotechnology Ltd. | Automatic injection devices having overmolded gripping surfaces |
US9878102B2 (en) | 2011-01-24 | 2018-01-30 | Abbvie Biotechnology Ltd. | Automatic injection devices having overmolded gripping surfaces |
EP2676677A4 (en) * | 2011-02-17 | 2015-02-11 | Kyowa Hakko Kirin Co Ltd | HIGHLY CONCENTRATED PHARMACEUTICAL PREPARATION WITH ANTIBODIES TO CD40 |
US9125893B2 (en) | 2011-02-17 | 2015-09-08 | Kyowa Hakko Kirin Co., Ltd. | Highly concentrated anti-CD40 antibody pharmaceutical preparation |
EP2676677A1 (en) * | 2011-02-17 | 2013-12-25 | Kyowa Hakko Kirin Co., Ltd. | Highly concentrated anti-cd40 antibody pharmaceutical preparation |
US11008389B2 (en) | 2011-03-16 | 2021-05-18 | Sanofi | Uses of a dual V region antibody-like protein |
US9365645B1 (en) | 2011-04-27 | 2016-06-14 | Abbvie, Inc. | Methods for controlling the galactosylation profile of recombinantly-expressed proteins |
US9062106B2 (en) | 2011-04-27 | 2015-06-23 | Abbvie Inc. | Methods for controlling the galactosylation profile of recombinantly-expressed proteins |
US9090688B2 (en) | 2011-04-27 | 2015-07-28 | Abbvie Inc. | Methods for controlling the galactosylation profile of recombinantly-expressed proteins |
US9505834B2 (en) | 2011-04-27 | 2016-11-29 | Abbvie Inc. | Methods for controlling the galactosylation profile of recombinantly-expressed proteins |
US9255143B2 (en) | 2011-04-27 | 2016-02-09 | Abbvie Inc. | Methods for controlling the galactosylation profile of recombinantly-expressed proteins |
US9683050B2 (en) | 2011-05-02 | 2017-06-20 | Immunomedics, Inc. | Stable compositions of high-concentration allotype-selected antibodies for small-volume administration |
US8658773B2 (en) | 2011-05-02 | 2014-02-25 | Immunomedics, Inc. | Ultrafiltration concentration of allotype selected antibodies for small-volume administration |
US9180205B2 (en) | 2011-05-02 | 2015-11-10 | Immunomedics, Inc. | Stable compositions of high-concentration allotype-selected antibodies for small-volume administration |
US9963516B2 (en) | 2011-05-02 | 2018-05-08 | Immunomedics, Inc. | Stable compositions of high-concentration allotype-selected antibodies for small-volume administration |
US9468689B2 (en) | 2011-05-02 | 2016-10-18 | Immunomedics, Inc. | Ultrafiltration concentration of allotype selected antibodies for small-volume administration |
US8926980B2 (en) | 2011-07-11 | 2015-01-06 | Camas Incorporated | Compositions against bacterial toxins |
WO2013009843A1 (en) * | 2011-07-11 | 2013-01-17 | Camas Incorporated | Compositions against bacterial toxins |
EP3009450A1 (en) * | 2011-07-19 | 2016-04-20 | Glaxo Group Limited | Liquid formulation comprising adalimumab and an acetate buffer |
US9683033B2 (en) | 2012-04-20 | 2017-06-20 | Abbvie, Inc. | Cell culture methods to reduce acidic species |
US9359434B2 (en) | 2012-04-20 | 2016-06-07 | Abbvie, Inc. | Cell culture methods to reduce acidic species |
US9150645B2 (en) | 2012-04-20 | 2015-10-06 | Abbvie, Inc. | Cell culture methods to reduce acidic species |
US9181572B2 (en) | 2012-04-20 | 2015-11-10 | Abbvie, Inc. | Methods to modulate lysine variant distribution |
US9708400B2 (en) | 2012-04-20 | 2017-07-18 | Abbvie, Inc. | Methods to modulate lysine variant distribution |
US9505833B2 (en) | 2012-04-20 | 2016-11-29 | Abbvie Inc. | Human antibodies that bind human TNF-alpha and methods of preparing the same |
US9193787B2 (en) | 2012-04-20 | 2015-11-24 | Abbvie Inc. | Human antibodies that bind human TNF-alpha and methods of preparing the same |
US9334319B2 (en) | 2012-04-20 | 2016-05-10 | Abbvie Inc. | Low acidic species compositions |
US9346879B2 (en) | 2012-04-20 | 2016-05-24 | Abbvie Inc. | Protein purification methods to reduce acidic species |
US9957318B2 (en) | 2012-04-20 | 2018-05-01 | Abbvie Inc. | Protein purification methods to reduce acidic species |
US9249182B2 (en) | 2012-05-24 | 2016-02-02 | Abbvie, Inc. | Purification of antibodies using hydrophobic interaction chromatography |
WO2013186230A1 (en) * | 2012-06-12 | 2013-12-19 | Boehringer Ingelheim International Gmbh | Pharmaceutical formulation for a therapeutic antibody |
US9278131B2 (en) | 2012-08-10 | 2016-03-08 | Adocia | Process for lowering the viscosity of highly concentrated protein solutions |
US9290568B2 (en) | 2012-09-02 | 2016-03-22 | Abbvie, Inc. | Methods to control protein heterogeneity |
US9206390B2 (en) | 2012-09-02 | 2015-12-08 | Abbvie, Inc. | Methods to control protein heterogeneity |
US9234033B2 (en) | 2012-09-02 | 2016-01-12 | Abbvie, Inc. | Methods to control protein heterogeneity |
US9512214B2 (en) | 2012-09-02 | 2016-12-06 | Abbvie, Inc. | Methods to control protein heterogeneity |
KR101820582B1 (ko) * | 2012-09-05 | 2018-01-22 | 트라콘 파마수티칼즈, 인코포레이티드 | 항체 제제 및 이의 용도 |
EP2892559A4 (en) * | 2012-09-05 | 2016-05-11 | Tracon Pharmaceuticals Inc | ANTIBODY FORMULATIONS AND USES THEREOF |
US10195281B2 (en) | 2012-09-05 | 2019-02-05 | Tracon Pharmaceuticals, Inc. | Antibody formulations and uses thereof |
US10195275B2 (en) | 2012-09-07 | 2019-02-05 | Coherus Biosciences, Inc. | Stable aqueous formulations of adalimumab |
US10772960B2 (en) | 2012-09-07 | 2020-09-15 | Coherus Biosciences, Inc. | Stable aqueous formulations of adalimumab |
US10159732B2 (en) | 2012-09-07 | 2018-12-25 | Coherus Biosciences, Inc. | Stable aqueous formulations of adalimumab |
US10159733B2 (en) | 2012-09-07 | 2018-12-25 | Coherus Biosciences, Inc. | Stable aqueous formulations of adalimumab |
US10716852B2 (en) | 2012-09-07 | 2020-07-21 | Coherus Biosciences, Inc. | Stable aqueous formulations of adalimumab |
US10688183B2 (en) | 2012-09-07 | 2020-06-23 | Coherus Biosciences, Inc. | Stable aqueous formulations of adalimumab |
US10716853B2 (en) | 2012-09-07 | 2020-07-21 | Coherus Biosciences, Inc. | Stable aqueous formulations of adalimumab |
US20160031982A1 (en) * | 2012-09-07 | 2016-02-04 | Coherus Biosciences, Inc. | Stable Aqueous Formulations of Adalimumab |
US10155039B2 (en) | 2012-09-07 | 2018-12-18 | Coherus Biosciences, Inc. | Stable aqueous formulations of adalimumab |
US9808525B2 (en) * | 2012-09-07 | 2017-11-07 | Coherus Biosciences, Inc. | Stable aqueous formulations of adalimumab |
US10799585B2 (en) | 2012-09-07 | 2020-10-13 | Coherus Biosciences, Inc. | Stable aqueous formulations of adalimumab |
US10716854B2 (en) | 2012-09-07 | 2020-07-21 | Coherus Biosciences, Inc. | Stable aqueous formulations of adalimumab |
US10722579B2 (en) | 2012-09-07 | 2020-07-28 | Coherus Biosciences, Inc. | Stable aqueous formulations of adalimumab |
US10207000B2 (en) | 2012-09-07 | 2019-02-19 | Coherus Biosciences, Inc. | Stable aqueous formulations of adalimumab |
US10772959B2 (en) | 2012-09-07 | 2020-09-15 | Coherus Biosciences, Inc. | Stable aqueous formulations of adalimumab |
US10780163B2 (en) | 2012-09-07 | 2020-09-22 | Coherus Biosciences, Inc. | Stable aqueous formulations of adalimumab |
US10786566B2 (en) | 2012-09-07 | 2020-09-29 | Coherus Biosciences, Inc. | Stable aqueous formulations of adalimumab |
US10286072B2 (en) | 2012-09-07 | 2019-05-14 | Coherus Biosciences, Inc. | Methods of manufacturing stable aqueous formulations of adalimumab |
US10286071B2 (en) | 2012-09-07 | 2019-05-14 | Coherus Biosciences, Inc. | Syringe containing stable aqueous formulations of adalimumab |
WO2014114651A1 (en) * | 2013-01-24 | 2014-07-31 | Glaxosmithkline Intellectual Property Development Limited | Tnf-alpha antigen-binding proteins |
US9067990B2 (en) | 2013-03-14 | 2015-06-30 | Abbvie, Inc. | Protein purification using displacement chromatography |
US9499614B2 (en) | 2013-03-14 | 2016-11-22 | Abbvie Inc. | Methods for modulating protein glycosylation profiles of recombinant protein therapeutics using monosaccharides and oligosaccharides |
US8921526B2 (en) | 2013-03-14 | 2014-12-30 | Abbvie, Inc. | Mutated anti-TNFα antibodies and methods of their use |
US9708399B2 (en) | 2013-03-14 | 2017-07-18 | Abbvie, Inc. | Protein purification using displacement chromatography |
WO2014144960A2 (en) | 2013-03-15 | 2014-09-18 | Abbvie Biotherapeutics Inc. | Fc variants |
US10005835B2 (en) | 2013-04-29 | 2018-06-26 | Sanofi | Anti-IL-4/anti-IL-13 bispecific antibody formulations |
EP3003369A4 (en) * | 2013-05-28 | 2017-04-26 | Momenta Pharmaceuticals, Inc. | Pharmaceutical compositions comprising pyrophosphate |
EP3003369A1 (en) * | 2013-05-28 | 2016-04-13 | Momenta Pharmaceuticals, Inc. | Pharmaceutical compositions comprising pyrophosphate |
US20160136280A1 (en) * | 2013-06-24 | 2016-05-19 | Hoffmann-La Roche Inc. | Stable intravenous formulation |
WO2015035044A2 (en) | 2013-09-04 | 2015-03-12 | Abbvie Biotherapeutics Inc. | Fc VARIANTS WITH IMPROVED ANTIBODY-DEPENDENT CELL-MEDIATED CYTOTOXICITY |
US9598667B2 (en) | 2013-10-04 | 2017-03-21 | Abbvie Inc. | Use of metal ions for modulation of protein glycosylation profiles of recombinant proteins |
US9181337B2 (en) | 2013-10-18 | 2015-11-10 | Abbvie, Inc. | Modulated lysine variant species compositions and methods for producing and using the same |
US9085618B2 (en) | 2013-10-18 | 2015-07-21 | Abbvie, Inc. | Low acidic species compositions and methods for producing and using the same |
US9522953B2 (en) | 2013-10-18 | 2016-12-20 | Abbvie, Inc. | Low acidic species compositions and methods for producing and using the same |
US9200069B2 (en) | 2013-10-18 | 2015-12-01 | Abbvie, Inc. | Low acidic species compositions and methods for producing and using the same |
US8946395B1 (en) | 2013-10-18 | 2015-02-03 | Abbvie Inc. | Purification of proteins using hydrophobic interaction chromatography |
US9200070B2 (en) | 2013-10-18 | 2015-12-01 | Abbvie, Inc. | Low acidic species compositions and methods for producing and using the same |
US9017687B1 (en) | 2013-10-18 | 2015-04-28 | Abbvie, Inc. | Low acidic species compositions and methods for producing and using the same using displacement chromatography |
US9688752B2 (en) | 2013-10-18 | 2017-06-27 | Abbvie Inc. | Low acidic species compositions and methods for producing and using the same using displacement chromatography |
US9499616B2 (en) | 2013-10-18 | 2016-11-22 | Abbvie Inc. | Modulated lysine variant species compositions and methods for producing and using the same |
US9266949B2 (en) | 2013-10-18 | 2016-02-23 | Abbvie, Inc. | Low acidic species compositions and methods for producing and using the same |
US9315574B2 (en) | 2013-10-18 | 2016-04-19 | Abbvie, Inc. | Low acidic species compositions and methods for producing and using the same |
US9326935B2 (en) * | 2013-11-08 | 2016-05-03 | Eli Lilly And Company | Atomoxetine solution |
US9550826B2 (en) | 2013-11-15 | 2017-01-24 | Abbvie Inc. | Glycoengineered binding protein compositions |
US10493152B2 (en) | 2014-05-23 | 2019-12-03 | Fresenius Kabi Deutschland Gmbh | Adalimumab formulations |
US11752209B2 (en) | 2014-05-23 | 2023-09-12 | Fresenius Kabi Deutschland Gmbh | Liquid pharmaceutical composition |
WO2015177059A1 (en) * | 2014-05-23 | 2015-11-26 | Ares Trading S.A. | Liquid pharmaceutical composition |
US10729769B2 (en) | 2014-05-23 | 2020-08-04 | Fresenius Kabi Deutschland Gmbh | Liquid pharmaceutical composition |
US10426832B2 (en) | 2014-05-23 | 2019-10-01 | Fresenius Kabi Deutschland Gmbh | Liquid pharmaceutical composition |
US10426833B2 (en) | 2014-05-23 | 2019-10-01 | Fresenius Kabi Deutschland Gmbh | Liquid pharmaceutical composition |
US10772961B2 (en) | 2014-05-23 | 2020-09-15 | Fresenius Kabi Deutschland Gmbh | Liquid pharmaceutical composition |
US11752208B2 (en) | 2014-05-23 | 2023-09-12 | Fresenius Kabi Deutschland Gmbh | Liquid pharmaceutical composition |
US11707524B2 (en) | 2014-05-23 | 2023-07-25 | Fresenius Kabi Deutschland Gmbh | Liquid pharmaceutical composition |
US11712471B2 (en) | 2014-05-23 | 2023-08-01 | Fresenius Kabi Deustschland GmbH | Liquid pharmaceutical composition |
AU2020286276B2 (en) * | 2014-05-23 | 2023-06-01 | Fresenius Kabi Deutschland Gmbh | Liquid pharmaceutical composition |
CN111939257A (zh) * | 2014-05-23 | 2020-11-17 | 费森尤斯卡比德国有限公司 | 液体药物组合物 |
EP3741358A1 (en) * | 2014-05-23 | 2020-11-25 | Fresenius Kabi Deutschland GmbH | Liquid pharmaceutical composition |
EP3939566A1 (en) * | 2014-05-23 | 2022-01-19 | Fresenius Kabi Deutschland GmbH | Liquid pharmaceutical composition |
EP2946767A1 (en) * | 2014-05-23 | 2015-11-25 | Ares Trading S.A. | Liquid pharmaceutical composition |
US10336831B2 (en) | 2014-11-12 | 2019-07-02 | Tracon Pharmaceuticals, Inc. | Use of anti-endoglin antibodies for treating ocular fibrosis |
US10155820B2 (en) | 2014-11-12 | 2018-12-18 | Tracon Pharmaceuticals, Inc. | Anti-endoglin antibodies and uses thereof |
US9926375B2 (en) | 2014-11-12 | 2018-03-27 | Tracon Pharmaceuticals, Inc. | Anti-endoglin antibodies and uses thereof |
EP3053573A1 (en) * | 2015-02-06 | 2016-08-10 | Ares Trading S.A. | Liquid pharmaceutical composition |
EP3053572A1 (en) * | 2015-02-06 | 2016-08-10 | Ares Trading S.A. | Liquid pharmaceutical composition |
WO2016124588A1 (en) * | 2015-02-06 | 2016-08-11 | Ares Trading S.A. | Liquid pharmaceutical composition |
US10179811B2 (en) | 2015-04-10 | 2019-01-15 | Fresenius Kabi Deutschland Gmbh | Methods of treating Crohn's disease or ulcerative colitis using an induction dosing regimen comprising anti-TNF-alpha antibody |
US10689440B2 (en) | 2015-04-10 | 2020-06-23 | Fresenius Kabi Deutschland Gmbh | Method of treating Crohn's disease and ulcerative colitis by using an induction dosing regimen of adalimumab |
US10669333B2 (en) | 2015-04-10 | 2020-06-02 | Fresenius Kabi Deutschland Gmbh | Method of treating a tumor necrosis factor α (TNFα)-related disorder by using an induction dosing regimen of adalimumab |
US11229702B1 (en) | 2015-10-28 | 2022-01-25 | Coherus Biosciences, Inc. | High concentration formulations of adalimumab |
US11071782B2 (en) | 2016-04-20 | 2021-07-27 | Coherus Biosciences, Inc. | Method of filling a container with no headspace |
US11576971B2 (en) | 2016-04-20 | 2023-02-14 | Coherus Biosciences, Inc. | Method of filling a container with no headspace |
US10307483B2 (en) | 2016-10-21 | 2019-06-04 | Amgen Inc. | Pharmaceutical formulations and methods of making the same |
US11491223B2 (en) | 2016-10-21 | 2022-11-08 | Amgen Inc. | Pharmaceutical formulations and methods of making the same |
US11534402B2 (en) | 2017-03-06 | 2022-12-27 | Arecor Limited | Liquid pharmaceutical composition |
US11534403B2 (en) | 2017-03-06 | 2022-12-27 | Arecor Limited | Liquid pharmaceutical composition |
US10799597B2 (en) | 2017-04-03 | 2020-10-13 | Immunomedics, Inc. | Subcutaneous administration of antibody-drug conjugates for cancer therapy |
WO2018184693A1 (en) * | 2017-04-07 | 2018-10-11 | Ares Trading S.A. | Liquid pharmaceutical composition |
US11608357B2 (en) | 2018-08-28 | 2023-03-21 | Arecor Limited | Stabilized antibody protein solutions |
US11634485B2 (en) | 2019-02-18 | 2023-04-25 | Eli Lilly And Company | Therapeutic antibody formulation |
Also Published As
Similar Documents
Publication | Publication Date | Title |
---|---|---|
US9732152B2 (en) | Formulation of human antibodies for treating TNF-alpha associated disorders |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
AS | Assignment |
Owner name: ABBOTT BIOTECHNOLOGY LTD., BERMUDA Free format text: ASSIGNMENT OF ASSIGNORS INTEREST;ASSIGNORS:KRAUSE, HANS-JUERGEN;BAUST, LISA;DICKES, MICHAEL;REEL/FRAME:014389/0458 Effective date: 20021212 |
|
STCB | Information on status: application discontinuation |
Free format text: ABANDONED -- FAILURE TO RESPOND TO AN OFFICE ACTION |
|
AS | Assignment |
Owner name: ABBVIE BIOTECHNOLOGY LTD., BERMUDA Free format text: CHANGE OF NAME;ASSIGNOR:ABBOTT BIOTECHNOLOGY LTD.;REEL/FRAME:031217/0148 Effective date: 20120625 |