[go: up one dir, main page]

IN2014CN03555A - - Google Patents

Download PDF

Info

Publication number
IN2014CN03555A
IN2014CN03555A IN3555CHN2014A IN2014CN03555A IN 2014CN03555 A IN2014CN03555 A IN 2014CN03555A IN 3555CHN2014 A IN3555CHN2014 A IN 3555CHN2014A IN 2014CN03555 A IN2014CN03555 A IN 2014CN03555A
Authority
IN
India
Prior art keywords
amyloidosis
prophylaxis
treatment
methods useful
antibody formulations
Prior art date
Application number
Other languages
English (en)
Inventor
Patrick Garidel
Isaac Craig Henderson
Pamela Klein
Original Assignee
Onclave Therapeutics Ltd
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Application filed by Onclave Therapeutics Ltd filed Critical Onclave Therapeutics Ltd
Publication of IN2014CN03555A publication Critical patent/IN2014CN03555A/en

Links

Classifications

    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/185Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
    • A61K31/19Carboxylic acids, e.g. valproic acid
    • A61K31/195Carboxylic acids, e.g. valproic acid having an amino group
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/185Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
    • A61K31/19Carboxylic acids, e.g. valproic acid
    • A61K31/195Carboxylic acids, e.g. valproic acid having an amino group
    • A61K31/197Carboxylic acids, e.g. valproic acid having an amino group the amino and the carboxyl groups being attached to the same acyclic carbon chain, e.g. gamma-aminobutyric acid [GABA], beta-alanine, epsilon-aminocaproic acid or pantothenic acid
    • A61K31/198Alpha-amino acids, e.g. alanine or edetic acid [EDTA]
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/325Carbamic acids; Thiocarbamic acids; Anhydrides or salts thereof
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/395Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/44Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/445Non condensed piperidines, e.g. piperocaine
    • A61K31/4523Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems
    • A61K31/454Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. pimozide, domperidone
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/69Boron compounds
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00Medicinal preparations containing peptides
    • A61K38/04Peptides having up to 20 amino acids in a fully defined sequence; Derivatives thereof
    • A61K38/07Tetrapeptides
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00Medicinal preparations containing antigens or antibodies
    • A61K39/395Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
    • A61K39/39533Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum against materials from animals
    • A61K39/3955Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum against materials from animals against proteinaceous materials, e.g. enzymes, hormones, lymphokines
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/16Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing nitrogen, e.g. nitro-, nitroso-, azo-compounds, nitriles, cyanates
    • A61K47/18Amines; Amides; Ureas; Quaternary ammonium compounds; Amino acids; Oligopeptides having up to five amino acids
    • A61K47/183Amino acids, e.g. glycine, EDTA or aspartame
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/22Heterocyclic compounds, e.g. ascorbic acid, tocopherol or pyrrolidones
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/26Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00Medicinal preparations characterised by special physical form
    • A61K9/14Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
    • A61K9/19Particulate 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
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/04Drugs 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
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00Drugs for disorders of the respiratory system
    • A61P11/08Bronchodilators
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P13/00Drugs for disorders of the urinary system
    • A61P13/02Drugs for disorders of the urinary system of urine or of the urinary tract, e.g. urine acidifiers
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P13/00Drugs for disorders of the urinary system
    • A61P13/12Drugs for disorders of the urinary system of the kidneys
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00Drugs for dermatological disorders
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00Drugs for dermatological disorders
    • A61P17/06Antipsoriatics
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P19/00Drugs for skeletal disorders
    • A61P19/02Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00Drugs for disorders of the nervous system
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00Drugs for disorders of the nervous system
    • A61P25/28Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/04Antibacterial agents
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/04Antibacterial agents
    • A61P31/06Antibacterial agents for tuberculosis
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/04Antibacterial agents
    • A61P31/08Antibacterial agents for leprosy
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00Antineoplastic agents
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P7/00Drugs for disorders of the blood or the extracellular fluid
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K16/00Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • C07K16/18Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00Medicinal preparations containing antigens or antibodies
    • A61K2039/505Medicinal preparations containing antigens or antibodies comprising antibodies
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00Medicinal preparations containing antigens or antibodies
    • A61K2039/545Medicinal preparations containing antigens or antibodies characterised by the dose, timing or administration schedule
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00Medicinal preparations containing antigens or antibodies
    • A61K39/395Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
    • A61K39/39591Stabilisation, fragmentation
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K2317/00Immunoglobulins specific features
    • C07K2317/10Immunoglobulins specific features characterized by their source of isolation or production
    • C07K2317/14Specific host cells or culture conditions, e.g. components, pH or temperature
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K2317/00Immunoglobulins specific features
    • C07K2317/20Immunoglobulins specific features characterized by taxonomic origin
    • C07K2317/24Immunoglobulins specific features characterized by taxonomic origin containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K2317/00Immunoglobulins specific features
    • C07K2317/40Immunoglobulins specific features characterized by post-translational modification
    • C07K2317/41Glycosylation, sialylation, or fucosylation
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K2317/00Immunoglobulins specific features
    • C07K2317/50Immunoglobulins specific features characterized by immunoglobulin fragments
    • C07K2317/56Immunoglobulins specific features characterized by immunoglobulin fragments variable (Fv) region, i.e. VH and/or VL
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K2317/00Immunoglobulins specific features
    • C07K2317/50Immunoglobulins specific features characterized by immunoglobulin fragments
    • C07K2317/56Immunoglobulins specific features characterized by immunoglobulin fragments variable (Fv) region, i.e. VH and/or VL
    • C07K2317/565Complementarity determining region [CDR]
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K2317/00Immunoglobulins specific features
    • C07K2317/70Immunoglobulins specific features characterized by effect upon binding to a cell or to an antigen
    • C07K2317/76Antagonist effect on antigen, e.g. neutralization or inhibition of binding

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Engineering & Computer Science (AREA)
  • Epidemiology (AREA)
  • Organic Chemistry (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Immunology (AREA)
  • Biochemistry (AREA)
  • Molecular Biology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Oil, Petroleum & Natural Gas (AREA)
  • Microbiology (AREA)
  • Mycology (AREA)
  • Communicable Diseases (AREA)
  • Oncology (AREA)
  • Genetics & Genomics (AREA)
  • Biophysics (AREA)
  • Biomedical Technology (AREA)
  • Neurosurgery (AREA)
  • Neurology (AREA)
  • Endocrinology (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Rheumatology (AREA)
  • Urology & Nephrology (AREA)
  • Pulmonology (AREA)
  • Dermatology (AREA)
  • Physical Education & Sports Medicine (AREA)
  • Psychiatry (AREA)
  • Hospice & Palliative Care (AREA)
  • Hematology (AREA)
IN3555CHN2014 2011-10-25 2012-10-25 IN2014CN03555A (da)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US201161551406P 2011-10-25 2011-10-25
PCT/US2012/061950 WO2013063284A1 (en) 2011-10-25 2012-10-25 Antibody formulations and methods

Publications (1)

Publication Number Publication Date
IN2014CN03555A true IN2014CN03555A (da) 2015-07-03

Family

ID=48168501

Family Applications (1)

Application Number Title Priority Date Filing Date
IN3555CHN2014 IN2014CN03555A (da) 2011-10-25 2012-10-25

Country Status (19)

Country Link
US (6) US9089529B2 (da)
EP (2) EP4088736A1 (da)
JP (6) JP6431372B2 (da)
KR (2) KR102276161B1 (da)
CN (2) CN107233569B (da)
AU (4) AU2012328739B2 (da)
BR (1) BR112014009866A2 (da)
CA (1) CA2853112C (da)
CL (2) CL2014001081A1 (da)
CO (1) CO7020867A2 (da)
EA (1) EA037797B1 (da)
HK (2) HK1198689A1 (da)
IL (1) IL232213B (da)
IN (1) IN2014CN03555A (da)
MX (2) MX391043B (da)
PE (2) PE20141413A1 (da)
PH (1) PH12014500904B1 (da)
SG (2) SG10201604104PA (da)
WO (1) WO2013063284A1 (da)

Families Citing this family (18)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
MY165038A (en) 2011-10-28 2018-02-28 Prothena Biosciences Ltd Humanized antibodies that recognize alpha-synuclein
WO2013075740A1 (en) 2011-11-23 2013-05-30 Sanofi Antibody purification method
EP2682168A1 (en) * 2012-07-02 2014-01-08 Millipore Corporation Purification of biological molecules
EP2994485B1 (en) * 2013-05-06 2018-01-10 Sanofi Continuous multistep process for purifying antibodies
US10513555B2 (en) * 2013-07-04 2019-12-24 Prothena Biosciences Limited Antibody formulations and methods
WO2017189964A2 (en) 2016-04-29 2017-11-02 Voyager Therapeutics, Inc. Compositions for the treatment of disease
EP3448874A4 (en) 2016-04-29 2020-04-22 Voyager Therapeutics, Inc. COMPOSITIONS FOR TREATING A DISEASE
MA45552A (fr) * 2016-06-30 2019-05-08 Prothena Biosciences Ltd Compositions destinées au traitement de l'amylose
WO2018173584A1 (ja) 2017-03-23 2018-09-27 ソニー株式会社 ビーム照射装置、および検出機能付きプロジェクタ
CN117924478A (zh) 2017-06-29 2024-04-26 纽约哥伦比亚大学理事会 治疗淀粉样沉积疾病的嵌合抗体和生产方法
US11382974B2 (en) * 2017-08-01 2022-07-12 The Trustees Of Columbia University In The City Of New York Methods and compositions for treatment of amyloid deposition diseases
US12247060B2 (en) 2018-01-09 2025-03-11 Marengo Therapeutics, Inc. Calreticulin binding constructs and engineered T cells for the treatment of diseases
CA3095100A1 (en) * 2018-03-23 2019-09-26 Prothena Biosciences Limited Treatment and prophylaxis of amyloidosis
US12018069B2 (en) 2018-06-28 2024-06-25 The Trustees Of Columbia University In The City Of New York Methods and compositions for imaging amyloid deposits
JOP20210220A1 (ar) * 2019-02-12 2023-01-30 Prothena Biosciences Ltd معالجة الداء النشواني من النوع خفيف السلسلة بتوليفة من أجسام مضادة أحادية النسيلة ضد سلاسل الغلوبيولين المناعي الخفيفة وجزيء الغشاء الخلوي cd38 على خلايا مناعية منتجة للأجسام المضادة وخلايا مناعية أخرى
JOP20210229A1 (ar) 2019-02-18 2023-01-30 Lilly Co Eli صيغة جسم مضاد علاجي
CA3132780A1 (en) 2019-03-05 2020-09-10 Prothena Biosciences Limited Methods of treating al amyloidosis
WO2024081329A1 (en) * 2022-10-12 2024-04-18 Marengo Therapeutics, Inc. Multifunctional molecules binding to tcr and uses thereof

Family Cites Families (141)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE3682047D1 (de) 1985-07-09 1991-11-21 Quadrant Bioresources Ltd Beschuetzung von proteinen und aehnlichem.
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
GB8921222D0 (en) 1989-09-20 1989-11-08 Riker Laboratories Inc Medicinal aerosol formulations
US5945098A (en) 1990-02-01 1999-08-31 Baxter International Inc. Stable intravenously-administrable immune globulin preparation
US6165500A (en) 1990-08-24 2000-12-26 Idea Ag Preparation for the application of agents in mini-droplets
WO1992018147A1 (en) 1991-04-19 1992-10-29 Affinity Biotech, Inc. Convertible microemulsion formulations
US5334380A (en) 1991-09-27 1994-08-02 Board Of Regents, The University Of Texas System Anti-endotoxin, interleukin-1 receptor antagonist and anti-tumor necrosis factor antibody with arginine-free formulations for the treatment of hypotension
WO1993005780A1 (en) 1991-09-27 1993-04-01 Board Of Regents, The University Of Texas System Amino acids containing parenteral formulations for the treatment of hypotension and related pathologies
DE69306755T2 (de) 1992-01-21 1997-04-10 Stanford Res Inst Int Verbessertes verfahren zur herstellung von mikronisierter polypeptidarzneimitteln
DE69331930T2 (de) 1992-02-18 2003-01-09 Pharmos Corp., New York Trockene zusammensetzungen zur herstellung von emulsionen im submikron-bereich
IL101007A (en) 1992-02-18 1997-08-14 Pharmos Ltd Dry stable compositions prepared by lyophilization
US6582728B1 (en) 1992-07-08 2003-06-24 Inhale Therapeutic Systems, Inc. Spray drying of macromolecules to produce inhaleable dry powders
WO1994019020A1 (en) 1993-02-23 1994-09-01 Genentech, Inc. Excipient stabilization of polypeptides treated with organic solvents
IS1796B (is) 1993-06-24 2001-12-31 Ab Astra Fjölpeptíð lyfjablanda til innöndunar sem einnig inniheldur eykjaefnasamband
US6794357B1 (en) 1993-06-24 2004-09-21 Astrazeneca Ab Compositions for inhalation
US5707648A (en) 1993-11-17 1998-01-13 Lds Technologies, Inc. Transparent liquid for encapsulated drug delivery
US6051256A (en) 1994-03-07 2000-04-18 Inhale Therapeutic Systems Dispersible macromolecule compositions and methods for their preparation and use
EP0788346B9 (en) 1994-03-18 2007-02-14 Supernus Pharmaceuticals, Inc. Emulsified drug delivery systems
EP0762897B1 (en) 1994-06-02 2003-04-02 Elan Drug Delivery Limited Method of preventing aggregation of proteins/peptides upon rehydration or thawing
US5580856A (en) 1994-07-15 1996-12-03 Prestrelski; Steven J. Formulation of a reconstituted protein, and method and kit for the production thereof
EE03593B1 (et) 1994-08-04 2002-02-15 Quadrant Holdings Cambridge Limited Molekulide reguleeritud vabastamisega tahked manustamissüsteemid ja nende valmistamismeetodid
US6290991B1 (en) 1994-12-02 2001-09-18 Quandrant Holdings Cambridge Limited Solid dose delivery vehicle and methods of making same
US5593824A (en) 1994-09-02 1997-01-14 Pharmacia Biotech, Inc. Biological reagent spheres
US6524557B1 (en) 1994-12-22 2003-02-25 Astrazeneca Ab Aerosol formulations of peptides and proteins
US5654337A (en) 1995-03-24 1997-08-05 II William Scott Snyder Topical formulation for local delivery of a pharmaceutically active agent
US6258341B1 (en) 1995-04-14 2001-07-10 Inhale Therapeutic Systems, Inc. Stable glassy state powder formulations
JP3708553B2 (ja) 1995-04-14 2005-10-19 ネクター セラピューティクス 向上した分散性を有する粉末型薬理組成物
US6309671B1 (en) 1995-04-14 2001-10-30 Inhale Therapeutic Systems Stable glassy state powder formulations
SK167597A3 (en) 1995-06-07 1998-10-07 Quadrant Holdings Cambridge Methods for stably incorporating substances within dry, foamed glass matrices and compositions obtained thereby
US6267958B1 (en) 1995-07-27 2001-07-31 Genentech, Inc. Protein formulation
ZA966075B (en) * 1995-07-27 1998-01-19 Genentech Inc Protein formulation.
US6685940B2 (en) 1995-07-27 2004-02-03 Genentech, Inc. Protein formulation
CA2226575C (en) 1995-07-27 2011-10-18 Genentech, Inc. Stabile isotonic lyophilized protein formulation
USRE38431E1 (en) 1995-12-01 2004-02-17 The American National Red Cross Methods of production and use of liquid formulations of plasma proteins
AU2063197A (en) 1996-03-04 1997-09-22 Massachusetts Institute Of Technology Materials and methods for enhancing cellular internalization
US6632648B1 (en) 1996-05-14 2003-10-14 Elan Drug Delivery Limited Methods of terminal sterilization of fibrinogen
EP0852951A1 (de) 1996-11-19 1998-07-15 Roche Diagnostics GmbH Stabile lyophilisierte pharmazeutische Zubereitungen von mono- oder polyklonalen Antikörpern
GB9705588D0 (en) 1997-03-18 1997-05-07 Anglia Research Foundation Stable particle in liquid formulations
WO1998043610A1 (en) 1997-04-03 1998-10-08 Elias Hakalehto A method for producing jelly sweets which contain antibodies
US7365166B2 (en) 1997-04-07 2008-04-29 Genentech, Inc. Anti-VEGF antibodies
ATE230277T1 (de) 1997-06-13 2003-01-15 Genentech Inc Stabilisierte antikörperformulierung
US6991790B1 (en) 1997-06-13 2006-01-31 Genentech, Inc. Antibody formulation
US6171586B1 (en) 1997-06-13 2001-01-09 Genentech, Inc. Antibody formulation
JP2002522354A (ja) 1997-09-19 2002-07-23 シャイア ラボラトリーズ,インコーポレイテッド 固溶体ビードレット
US6913745B1 (en) 1997-12-02 2005-07-05 Neuralab Limited Passive immunization of Alzheimer's disease
PT1018345E (pt) 1998-06-26 2009-01-23 Otsuka Pharma Co Ltd Composições secas solúveis em água
US6551613B1 (en) 1998-09-08 2003-04-22 Alza Corporation Dosage form comprising therapeutic formulation
NZ511072A (en) 1998-10-05 2004-03-26 Penn State Res Found Method for enhancing receptor-mediated cellular internalization using a composition of an active agent and a viscous material and an enhancer
US6645466B1 (en) 1998-11-13 2003-11-11 Jago Research Ag Dry powder for inhalation
ES2173679T3 (es) 1999-01-27 2002-10-16 Idea Ag Inmunizacion/transporte transnasal con vehiculos altamente adaptables.
US7258869B1 (en) 1999-02-08 2007-08-21 Alza Corporation Stable non-aqueous single phase viscous vehicles and formulations utilizing such vehicle
ES2379471T5 (es) 1999-02-08 2015-05-26 Intarcia Therapeutics, Inc Vehículos viscosos biocompatibles de fase única no acuosos y procedimientos para su preparación
AU3957400A (en) 1999-04-16 2000-11-02 Novo Nordisk A/S Dry, mouldable drug formulation
BR0010262A (pt) 1999-05-03 2002-01-15 Battelle Memorial Institute Composição para formar um aerossol, processo de preparação e de aerossolização de uma composição, e, dispositivo gerador de aerossol
CN100358577C (zh) 1999-05-07 2008-01-02 杰南技术公司 抗体在制备治疗哺乳动物自身免疫病的试剂中的用途
GB9914412D0 (en) 1999-06-22 1999-08-18 Worrall Eric E Method for the preservation of viruses,bacteria and biomolecules
US6309663B1 (en) 1999-08-17 2001-10-30 Lipocine Inc. Triglyceride-free compositions and methods for enhanced absorption of hydrophilic therapeutic agents
CN1286969C (zh) 1999-12-14 2006-11-29 热生物之星公司 多肽和抗原的稳定稀释剂
US7919113B2 (en) 1999-12-30 2011-04-05 Yissum Research Development Company Of The Hebrew University Of Jerusalem Dispersible concentrate lipospheres for delivery of active agents
US6465425B1 (en) 2000-02-10 2002-10-15 Alkermes Controlled Therapeutics, Inc. Microencapsulation and sustained release of biologically active acid-stable or free sulfhydryl-containing proteins
US6653062B1 (en) 2000-07-26 2003-11-25 Wisconsin Alumni Research Foundation Preservation and storage medium for biological materials
US7141236B2 (en) 2000-07-28 2006-11-28 Nektar Therapeutics Methods and compositions for delivering macromolecules to or via the respiratory tract
JP4340062B2 (ja) 2000-10-12 2009-10-07 ジェネンテック・インコーポレーテッド 粘度の減少した濃縮タンパク質製剤
EP3569610A3 (en) 2000-12-12 2020-03-18 Medlmmune, LLC Molecules with extended half lives, compositions and uses thereof
GB0113179D0 (en) 2001-05-31 2001-07-25 Novartis Ag Organic compounds
WO2003000282A1 (en) 2001-06-21 2003-01-03 Genentech, Inc. Sustained release formulation
SG2011076551A (en) 2001-06-26 2015-08-28 Amgen Inc Antibodies to opgl
US6646394B2 (en) * 2001-07-09 2003-11-11 Nissan Motor Co., Ltd. Control device for plurality of rotating electrical machines
DE60235013D1 (de) 2001-07-25 2010-02-25 Facet Biotech Corp Stabile lyophilisierte pharmazeutische formulierung des igg-antikörpers daclizumab
US20040023338A1 (en) * 2001-10-26 2004-02-05 Heavner George A. IL-4 mutein proteins, antibodies, compositions, methods and uses
AU2002363339B2 (en) 2001-11-08 2008-02-07 Abbvie Biotechnology Ltd Stable liquid pharmaceutical formulation of IGG antibodies
DE10163459A1 (de) 2001-12-21 2003-07-03 Merck Patent Gmbh Lyophilisierte Zubereitung enthaltend Antikörper gegen EGF-Rezeptor
PL213311B1 (pl) 2002-02-14 2013-02-28 Chugai Pharmaceutical Co Ltd Preparat roztworu zawierajacego przeciwcialo
PL215168B1 (pl) 2002-02-27 2013-10-31 Immunex Corp Formulacja polipeptydowa
US6982080B2 (en) 2002-03-15 2006-01-03 Wyeth Hydroxyethyl starch—containing polypeptide compositions
EP2591771A1 (en) 2002-04-11 2013-05-15 MedImmune, LLC Preservation of bioactive materials by freeze dried foam
US7258873B2 (en) 2002-04-11 2007-08-21 Medimmune Vaccines, Inc. Preservation of bioactive materials by spray drying
US7425618B2 (en) 2002-06-14 2008-09-16 Medimmune, Inc. Stabilized anti-respiratory syncytial virus (RSV) antibody formulations
US7132100B2 (en) 2002-06-14 2006-11-07 Medimmune, Inc. Stabilized liquid anti-RSV antibody formulations
US7601351B1 (en) 2002-06-26 2009-10-13 Human Genome Sciences, Inc. Antibodies against protective antigen
US20040120956A1 (en) * 2002-06-27 2004-06-24 Song Xiao-Yu R. CNGH0004 polypeptides, antibodies, compositions, methods and uses
US20040033228A1 (en) 2002-08-16 2004-02-19 Hans-Juergen Krause Formulation of human antibodies for treating TNF-alpha associated disorders
AR041881A1 (es) 2002-11-01 2005-06-01 Glaxosmithkline Biolog Sa Procedimiento de secado para la obtencion de un liquido altamente viscoso que conserva la antigenicidad o actividad de una agente activo y vacuna obtenida a partir de el
CA2504610C (en) 2002-11-12 2012-02-21 Elan Pharma International Ltd. Fast-disintegrating solid dosage forms being not friable and comprising pullulan
DK1572744T3 (da) 2002-12-16 2010-09-20 Genentech Inc Immunoglobulinvarianter og deres anvendelser
JP4680601B2 (ja) 2002-12-17 2011-05-11 メディミューン・エルエルシー 生物活性材料の高圧噴霧乾燥
ES2609010T3 (es) 2003-04-04 2017-04-18 Genentech, Inc. Formulaciones de anticuerpos y de proteínas a concentración elevada
MXPA05012259A (es) 2003-05-14 2006-04-18 Immunogen Inc Composicion de farmaco conjugado.
DE10333317A1 (de) 2003-07-22 2005-02-17 Biotecon Therapeutics Gmbh Formulierung für Proteinarzneimittel ohne Zusatz von humanem Serumalbumin (HSA)
AU2004287879C1 (en) 2003-11-04 2011-05-26 Novartis Vaccines And Diagnostics, Inc. Antagonist anti-CD40 monoclonal antibodies and methods for their use
US20050100965A1 (en) 2003-11-12 2005-05-12 Tariq Ghayur IL-18 binding proteins
DE10355251A1 (de) 2003-11-26 2005-06-23 Merck Patent Gmbh Pharmazeutische Zubereitung enthaltend einen Antikörper gegen den EGF-Rezeptor
SI21639A (sl) 2003-12-23 2005-06-30 LEK farmacevtska dru�ba d.d. Farmacevtski pripravek, ki vsebuje nemicelarne sulfobetaine
KR20070009637A (ko) 2004-03-24 2007-01-18 피디엘 바이오파르마 인코포레이티드 암 세포 증식을 억제하는 항α5β1 항체의 용도
US8043631B2 (en) 2004-04-02 2011-10-25 Au Jessie L S Tumor targeting drug-loaded particles
CA2562771C (en) 2004-04-12 2013-04-09 Medimmune, Inc. Anti-il-9 antibody formulations and uses thereof
GB0409795D0 (en) 2004-04-30 2004-06-09 Glaxosmithkline Biolog Sa Drying method
EP2287195B1 (en) 2004-07-01 2019-05-15 Novo Nordisk A/S Pan-kir2dl nk-receptor antibodies and their use in diagnostik and therapy
JO3000B1 (ar) 2004-10-20 2016-09-05 Genentech Inc مركبات أجسام مضادة .
US7780963B2 (en) * 2004-10-25 2010-08-24 Merck & Co., Inc. Anti-ADDL antibodies and uses thereof
JP5122969B2 (ja) 2004-11-09 2013-01-16 ノバガリ ファルマ エスア 安定な正のゼータ電位を有する眼科用水中油型乳剤
US20060124266A1 (en) * 2004-11-23 2006-06-15 Novozymes North America, Inc. Use of cyclodextrins for reducing deposits during paper production
US7541046B1 (en) 2005-01-04 2009-06-02 Gp Medical, Inc. Nanoparticles for protein drug delivery
US7910086B1 (en) 2005-01-04 2011-03-22 Gp Medical, Inc. Nanoparticles for protein drug delivery
US7879313B1 (en) 2005-01-04 2011-02-01 Gp Medical, Inc. Nanoparticles for protein drug delivery
US7919072B1 (en) 2005-01-04 2011-04-05 Gp Medical, Inc. Nanoparticles for protein drug delivery
US7993625B1 (en) 2005-01-04 2011-08-09 Gp Medical, Inc. Pharmaceutical composition of nanoparticles
US7897585B1 (en) 2005-01-04 2011-03-01 Gp Medical, Inc. Nanoparticles for protein drug delivery
US8048453B1 (en) 2005-01-04 2011-11-01 Gp Medical, Inc. Pharmaceutical composition of nanoparticles for protein drug delivery
GT200600031A (es) 2005-01-28 2006-08-29 Formulacion anticuerpo anti a beta
MY139088A (en) 2005-02-21 2009-08-28 Lg Life Sciences Ltd Sustained release composition of protein drug
CN101166763B (zh) 2005-04-18 2012-09-19 伊达研究和发展有限公司 稳定的抗乙肝病毒(hbv)抗体配制剂
KR100978684B1 (ko) 2005-04-22 2010-08-31 일라이 릴리 앤드 캄파니 Tgf 베타 1 특이적 항체
PE20061324A1 (es) 2005-04-29 2007-01-15 Centocor Inc Anticuerpos anti-il-6, composiciones, metodos y usos
EP1891110A2 (en) 2005-06-07 2008-02-27 Esbatech AG STABLE AND SOLUBLE ANTIBODIES INHIBITING TNF-alpha
CN103145842A (zh) 2005-06-30 2013-06-12 Abbvie公司 Il-12/p40结合蛋白
ES2390354T3 (es) 2005-07-22 2012-11-12 Amgen, Inc Liofilizados de proteínas concentrados, procedimientos y usos
JO2824B1 (en) * 2005-12-12 2014-09-15 اف . هوفمان لاروش ايه جي Antibody glycosylate in the changing region
EP1962907A2 (en) 2005-12-21 2008-09-03 Wyeth a Corporation of the State of Delaware Protein formulations with reduced viscosity and uses thereof
MY169492A (en) 2006-03-23 2019-04-15 Bioarctic Neuroscience Ab Improved protofibril selective antibodies and the use thereof
DE102006030164A1 (de) 2006-06-29 2008-01-03 Boehringer Ingelheim Pharma Gmbh & Co. Kg Inhalative Pulver
EP2468770B1 (en) * 2006-07-14 2017-12-20 AC Immune S.A. Humanized antibody against amyloid beta.
TW200833357A (en) 2006-10-20 2008-08-16 Amgen Inc Stable polypeptide formulations
GB0621707D0 (en) 2006-10-31 2006-12-13 Univ London Pharmacy Formulations for delivery via pressurised metered dose inhalers
US20110070225A1 (en) 2006-11-12 2011-03-24 Pierre Goldbach Beta antibody parenteral formulation
JP5410985B2 (ja) 2006-12-05 2014-02-05 クルセル ホランド ベー ヴェー 液体抗狂犬病抗体製剤
US7883664B2 (en) 2007-06-27 2011-02-08 University Of North Carolina At Charlotte Microwave drying process for vitrification of biologics
US8268354B2 (en) 2007-11-07 2012-09-18 Aridis Pharmaceuticals Sonic low pressure spray drying
KR101247418B1 (ko) 2007-12-21 2013-03-25 에프. 호프만-라 로슈 아게 항체 제형
PE20091174A1 (es) 2007-12-27 2009-08-03 Chugai Pharmaceutical Co Ltd Formulacion liquida con contenido de alta concentracion de anticuerpo
KR101603076B1 (ko) 2007-12-28 2016-03-14 프로테나 바이오사이언시즈 리미티드 아밀로이드증의 치료 및 예방
AR070316A1 (es) 2008-02-07 2010-03-31 Merck & Co Inc Antagonistas de pcsk9 (proproteina subtilisina-kexina tipo 9)
EP2303226B1 (en) 2008-06-25 2016-03-23 Endo Pharmaceuticals Solutions Inc. Sustained delivery of exenatide and other polypeptides
WO2009158432A2 (en) 2008-06-27 2009-12-30 Amgen Inc. Ang-2 inhibition to treat multiple sclerosis
EP2313435A4 (en) 2008-07-01 2012-08-08 Aveo Pharmaceuticals Inc FIBROBLAST GROWTH FACTOR RECEPTOR 3 (FGFR3) BINDING PROTEINS
AU2009288419B2 (en) 2008-08-27 2015-08-06 Merck Sharp & Dohme Llc Lyophilized formulatons of engineered anti-IL-23p19 antibodies
KR20140019035A (ko) 2008-09-19 2014-02-13 에프. 호프만-라 로슈 아게 신규한 항체 제형
KR101676887B1 (ko) * 2008-11-20 2016-11-16 제넨테크, 인크. 치료 단백질 제형
CN201401081Y (zh) 2009-03-26 2010-02-10 徐谦 一种两折型合页
CN201553504U (zh) * 2009-10-30 2010-08-18 浙江浦江缆索有限公司 一种悬索拉索成圈用120t成圈机

Also Published As

Publication number Publication date
CO7020867A2 (es) 2014-08-11
CN107233569B (zh) 2021-08-31
CN107233569A (zh) 2017-10-10
JP2023116817A (ja) 2023-08-22
AU2022202649A1 (en) 2022-05-12
AU2017258950A1 (en) 2017-11-30
US20140302021A1 (en) 2014-10-09
AU2012328739B2 (en) 2017-11-30
MX2014004786A (es) 2014-08-21
HK1198689A1 (en) 2015-05-29
CA2853112C (en) 2018-08-21
HK1243344A1 (zh) 2018-07-13
PE20141413A1 (es) 2014-10-25
AU2020201147A1 (en) 2020-03-05
JP2022033254A (ja) 2022-02-28
JP2017057218A (ja) 2017-03-23
CL2017002283A1 (es) 2018-05-18
JP6431372B2 (ja) 2018-11-28
EP2771029A4 (en) 2015-07-01
BR112014009866A2 (pt) 2018-09-04
WO2013063284A1 (en) 2013-05-02
EA037797B1 (ru) 2021-05-21
IL232213A0 (en) 2014-06-30
US20130295082A1 (en) 2013-11-07
JP2020063307A (ja) 2020-04-23
PH12014500904A1 (en) 2014-06-09
US20210077407A1 (en) 2021-03-18
IL232213B (en) 2019-03-31
EA201490850A1 (ru) 2015-03-31
US20160310430A1 (en) 2016-10-27
AU2012328739A1 (en) 2014-04-24
JP2014530917A (ja) 2014-11-20
CA2853112A1 (en) 2013-05-02
US20150344555A1 (en) 2015-12-03
KR102196009B1 (ko) 2021-01-04
CL2014001081A1 (es) 2014-11-21
SG10201604104PA (en) 2016-07-28
EP2771029A1 (en) 2014-09-03
US9089529B2 (en) 2015-07-28
KR20210003928A (ko) 2021-01-12
US9884020B2 (en) 2018-02-06
MX391043B (es) 2025-03-21
US10517830B2 (en) 2019-12-31
JP2018184478A (ja) 2018-11-22
PE20191242A1 (es) 2019-09-16
CN104023743A (zh) 2014-09-03
CN104023743B (zh) 2017-05-03
KR20140123475A (ko) 2014-10-22
US20180235887A1 (en) 2018-08-23
PH12014500904B1 (en) 2019-01-18
EP4088736A1 (en) 2022-11-16
MX354988B (es) 2018-03-28
NZ623606A (en) 2015-12-24
SG11201401360XA (en) 2014-05-29
KR102276161B1 (ko) 2021-07-14

Similar Documents

Publication Publication Date Title
IN2014CN03555A (da)
PH12015500525A1 (en) Formulations of enzalutamide
PH12016500611A1 (en) Compositions useful for treating disorders related to kit
MX2013011479A (es) Anticuerpos anti-fgfr4 y metodos de uso.
TN2013000310A1 (en) Effervescent composition in solid form for use in vaginal applications for the treatment of vaginal infections
PH12014500841B1 (en) ANTI-HtrA1 ANTIBODIES AND METHODS OF USE
PH12014501427B1 (en) Anti-phf-tau antibodies and their uses
MX2014002053A (es) Anticuerpos anti -mcsp y metodos de uso.
IN2015DN00127A (da)
EP2771030A4 (en) COMPOSITIONS AND METHOD FOR THE TREATMENT OF PROTEINOPATHIES
TN2013000378A1 (en) Anti - sclerostin antibody crystals and formulations thereof
IN2014DN11201A (da)
MX360774B (es) Antagonistas de progesterona.
IN2014CN04014A (da)
GB201109238D0 (en) Antibodies
UA115305C2 (uk) Композиції hyr1-похідних і способи лікування ними
IN2014DN00254A (da)
MX347541B (es) Analogos de acido sialico.
GB201107985D0 (en) Process
EP2685820A4 (en) COMPOSITIONS AND METHODS FOR TREATING INFECTIONS
AU2012900286A0 (en) "Methods of treatment or prophylaxis"
MY168958A (en) Intermediates and processes for preparing compounds
UA72478U (ru) Применение полентара как средства фригопротекторного действия
AU2011902129A0 (en) Compositions for Therapy and Methods of Treatment
AU2011901902A0 (en) Methods and compositions for the treatment of melanoma