MY194936A - Antibodies And Methods Of Use - Google Patents

Antibodies And Methods Of Use

Info

Publication number
MY194936A
MY194936A MYPI2016000855A MYPI2016000855A MY194936A MY 194936 A MY194936 A MY 194936A MY PI2016000855 A MYPI2016000855 A MY PI2016000855A MY PI2016000855 A MYPI2016000855 A MY PI2016000855A MY 194936 A MY194936 A MY 194936A
Authority
MY
Malaysia
Prior art keywords
methods
fgfr1
antibodies
binds
klb
Prior art date
Application number
MYPI2016000855A
Other languages
English (en)
Inventor
Yan Wu
Yongmei Chen
Junichiro Sonoda
James Ernst
Hok Seon Kim
Christoph Spiess
Scott Stawicki
Original Assignee
Genentech Inc
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
Family has litigation
First worldwide family litigation filed litigation Critical https://patents.darts-ip.com/?family=52347471&utm_source=google_patent&utm_medium=platform_link&utm_campaign=public_patent_search&patent=MY194936(A) "Global patent litigation dataset” by Darts-ip is licensed under a Creative Commons Attribution 4.0 International License.
Application filed by Genentech Inc filed Critical Genentech Inc
Publication of MY194936A publication Critical patent/MY194936A/en

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies
    • C07K16/40—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against enzymes
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies
    • C07K16/18—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans
    • C07K16/28—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
    • C07K16/2863—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against receptors for growth factors, growth regulators
    • 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
    • A61P15/00—Drugs for genital or sexual disorders; Contraceptives
    • A61P15/08—Drugs for genital or sexual disorders; Contraceptives for gonadal disorders or for enhancing fertility, e.g. inducers of ovulation or of spermatogenesis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P21/00—Drugs for disorders of the muscular or neuromuscular system
    • A61P21/02—Muscle relaxants, e.g. for tetanus or cramps
    • 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
    • A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
    • A61P25/16—Anti-Parkinson drugs
    • 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
    • A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
    • 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
    • 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
    • A61P3/06—Antihyperlipidemics
    • 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
    • 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
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/12—Antihypertensives
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • C07K14/705—Receptors; Cell surface antigens; Cell surface determinants
    • C07K14/71—Receptors; Cell surface antigens; Cell surface determinants for growth factors; for growth regulators
    • 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
    • C07K2317/20—Immunoglobulins specific features characterized by taxonomic origin
    • C07K2317/24—Immunoglobulins specific features characterized by taxonomic origin containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/30—Immunoglobulins specific features characterized by aspects of specificity or valency
    • C07K2317/31—Immunoglobulins specific features characterized by aspects of specificity or valency multispecific
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/30—Immunoglobulins specific features characterized by aspects of specificity or valency
    • C07K2317/33—Crossreactivity, e.g. for species or epitope, or lack of said crossreactivity
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/30—Immunoglobulins specific features characterized by aspects of specificity or valency
    • C07K2317/34—Identification of a linear epitope shorter than 20 amino acid residues or of a conformational epitope defined by amino acid residues
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/40—Immunoglobulins specific features characterized by post-translational modification
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/40—Immunoglobulins specific features characterized by post-translational modification
    • C07K2317/41—Glycosylation, sialylation, or fucosylation
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
    • C07K2317/51—Complete heavy chain or Fd fragment, i.e. VH + CH1
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
    • C07K2317/515—Complete light chain, i.e. VL + CL
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
    • C07K2317/52—Constant or Fc region; Isotype
    • C07K2317/524—CH2 domain
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
    • C07K2317/55—Fab or Fab'
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
    • C07K2317/56—Immunoglobulins specific features characterized by immunoglobulin fragments variable (Fv) region, i.e. VH and/or VL
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
    • C07K2317/56—Immunoglobulins specific features characterized by immunoglobulin fragments variable (Fv) region, i.e. VH and/or VL
    • C07K2317/565—Complementarity determining region [CDR]
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
    • C07K2317/56—Immunoglobulins specific features characterized by immunoglobulin fragments variable (Fv) region, i.e. VH and/or VL
    • C07K2317/567—Framework region [FR]
    • 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
    • C07K2317/71—Decreased effector function due to an Fc-modification
    • 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
    • C07K2317/75—Agonist effect on antigen
    • 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

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Animal Behavior & Ethology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Diabetes (AREA)
  • Immunology (AREA)
  • Genetics & Genomics (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Molecular Biology (AREA)
  • Biophysics (AREA)
  • Biochemistry (AREA)
  • Neurology (AREA)
  • Obesity (AREA)
  • Hematology (AREA)
  • Biomedical Technology (AREA)
  • Neurosurgery (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Endocrinology (AREA)
  • Reproductive Health (AREA)
  • Cell Biology (AREA)
  • Zoology (AREA)
  • Toxicology (AREA)
  • Emergency Medicine (AREA)
  • Pain & Pain Management (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Hospice & Palliative Care (AREA)
  • Orthopedic Medicine & Surgery (AREA)
  • Physical Education & Sports Medicine (AREA)
  • Gynecology & Obstetrics (AREA)
MYPI2016000855A 2013-12-23 2014-12-23 Antibodies And Methods Of Use MY194936A (en)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US201361920396P 2013-12-23 2013-12-23
US201462081435P 2014-11-18 2014-11-18
PCT/US2014/072245 WO2015100366A1 (en) 2013-12-23 2014-12-23 Antibodies and methods of use

Publications (1)

Publication Number Publication Date
MY194936A true MY194936A (en) 2022-12-27

Family

ID=52347471

Family Applications (1)

Application Number Title Priority Date Filing Date
MYPI2016000855A MY194936A (en) 2013-12-23 2014-12-23 Antibodies And Methods Of Use

Country Status (30)

Country Link
US (7) US9873748B2 (enExample)
EP (2) EP3086807B1 (enExample)
JP (4) JP6687533B2 (enExample)
KR (3) KR20210144910A (enExample)
CN (2) CN105939727B (enExample)
AU (4) AU2014369872B2 (enExample)
BR (1) BR112016013960B1 (enExample)
CA (1) CA2929868C (enExample)
CL (1) CL2016001592A1 (enExample)
CR (1) CR20160338A (enExample)
DK (1) DK3086807T3 (enExample)
EA (1) EA036107B1 (enExample)
ES (1) ES2926375T3 (enExample)
HR (1) HRP20221088T1 (enExample)
HU (1) HUE059701T2 (enExample)
IL (3) IL245493B (enExample)
LT (1) LT3086807T (enExample)
MX (2) MX374976B (enExample)
MY (1) MY194936A (enExample)
NZ (1) NZ720765A (enExample)
PE (1) PE20161152A1 (enExample)
PH (1) PH12016500927A1 (enExample)
PL (1) PL3086807T3 (enExample)
PT (1) PT3086807T (enExample)
RS (1) RS63565B1 (enExample)
SG (2) SG10202007790WA (enExample)
SI (1) SI3086807T1 (enExample)
TW (2) TWI728373B (enExample)
UA (1) UA120357C2 (enExample)
WO (1) WO2015100366A1 (enExample)

Families Citing this family (22)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
TWI728373B (zh) 2013-12-23 2021-05-21 美商建南德克公司 抗體及使用方法
RS60593B1 (sr) 2014-01-24 2020-08-31 Ngm Biopharmaceuticals Inc Antitela koja vezuju domen 2 beta-kloto i postupci za njihovu upotrebu
MX373805B (es) 2014-03-25 2020-03-24 Regeneron Pharma Agonistas de receptor fgf21 y usos del mismo.
CA2961439A1 (en) 2014-11-05 2016-05-12 Genentech, Inc. Anti-fgfr2/3 antibodies and methods using same
US10800843B2 (en) 2015-07-29 2020-10-13 Ngm Biopharmaceuticals, Inc. Beta klotho-binding proteins
EP3331914A1 (en) * 2015-08-03 2018-06-13 Novartis AG Methods of treating fgf21-associated disorders
MX2018003536A (es) 2015-09-24 2018-08-01 Genentech Inc Metodos para el tratamiento de la epilepsia.
JP7027321B2 (ja) 2015-11-03 2022-03-01 ヤンセン バイオテツク,インコーポレーテツド 抗cd38抗体の皮下製剤及びその使用
WO2017079768A1 (en) * 2015-11-08 2017-05-11 Genentech, Inc. Methods of screening for multispecific antibodies
US11530277B2 (en) 2016-04-20 2022-12-20 Regeneron Pharmaceuticals, Inc. Compositions and methods for making antibodies based on use of an expression-enhancing locus
BR112018071283A2 (pt) 2016-04-20 2019-02-12 Regeneron Pharma célula, conjunto de vetores para expressar uma proteína de ligação a antígeno biespecífica em uma célula, conjunto de vetores, método, e, método para produção de uma proteína de ligação a antígeno.
CA3052911A1 (en) 2017-02-08 2018-08-16 Novartis Ag Fgf21 mimetic antibodies and uses thereof
IL268568B2 (en) 2017-02-10 2024-03-01 Mayo Found Medical Education & Res TRAILshort ANTIBODY AND METHODS OF USE
CN107966525B (zh) * 2017-11-06 2023-10-20 中国矿业大学(北京) 一种13co2量化脉冲标记植物的方法
TW202011029A (zh) 2018-04-04 2020-03-16 美商建南德克公司 偵測及定量fgf21之方法
AU2020379735A1 (en) 2019-11-05 2022-05-26 Regeneron Pharmaceuticals, Inc. N-terminal SCFV multispecific binding molecules
BR112023022878A2 (pt) 2021-05-04 2024-01-23 Regeneron Pharma Agonistas do receptor fgf21 multiespecíficos e seus usos
WO2022270518A1 (ja) * 2021-06-21 2022-12-29 積水化学工業株式会社 受容体型チロシンキナーゼアゴニスト、細胞培養用培地組成物、及び未分化性維持組成物
WO2023046071A1 (zh) * 2021-09-23 2023-03-30 江苏恒瑞医药股份有限公司 抗klb抗体及用途
EP4458852A4 (en) * 2021-12-30 2026-04-15 Shanghai Jmt Bio Tech Co Ltd ANTI-KLOTHO ANTIBODY AND ITS USE
WO2025188901A1 (en) 2024-03-05 2025-09-12 Halozyme, Inc. Combination therapy with antibody-drug conjugates and hyaluronidases
CN119431588B (zh) * 2024-11-11 2026-08-11 北京春冠利亚生物技术有限公司 分离的免疫细胞的制备方法及其在治疗癌症中的应用

Family Cites Families (146)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4475196A (en) 1981-03-06 1984-10-02 Zor Clair G Instrument for locating faults in aircraft passenger reading light and attendant call control system
US4447233A (en) 1981-04-10 1984-05-08 Parker-Hannifin Corporation Medication infusion pump
US4474893A (en) 1981-07-01 1984-10-02 The University of Texas System Cancer Center Recombinant monoclonal antibodies
US4439196A (en) 1982-03-18 1984-03-27 Merck & Co., Inc. Osmotic drug delivery system
US4447224A (en) 1982-09-20 1984-05-08 Infusaid Corporation Variable flow implantable infusion apparatus
US4487603A (en) 1982-11-26 1984-12-11 Cordis Corporation Implantable microinfusion pump system
US4816567A (en) 1983-04-08 1989-03-28 Genentech, Inc. Recombinant immunoglobin preparations
US4486194A (en) 1983-06-08 1984-12-04 James Ferrara Therapeutic device for administering medicaments through the skin
US4596556A (en) 1985-03-25 1986-06-24 Bioject, Inc. Hypodermic injection apparatus
US4737456A (en) 1985-05-09 1988-04-12 Syntex (U.S.A.) Inc. Reducing interference in ligand-receptor binding assays
US4676980A (en) 1985-09-23 1987-06-30 The United States Of America As Represented By The Secretary Of The Department Of Health And Human Services Target specific cross-linked heteroantibodies
US6548640B1 (en) 1986-03-27 2003-04-15 Btg International Limited Altered antibodies
US4881175A (en) 1986-09-02 1989-11-14 Genex Corporation Computer based system and method for determining and displaying possible chemical structures for converting double- or multiple-chain polypeptides to single-chain polypeptides
US5260203A (en) 1986-09-02 1993-11-09 Enzon, Inc. Single polypeptide chain binding molecules
IL85035A0 (en) 1987-01-08 1988-06-30 Int Genetic Eng Polynucleotide molecule,a chimeric antibody with specificity for human b cell surface antigen,a process for the preparation and methods utilizing the same
JP3101690B2 (ja) 1987-03-18 2000-10-23 エス・ビィ・2・インコーポレイテッド 変性抗体の、または変性抗体に関する改良
US5013653A (en) 1987-03-20 1991-05-07 Creative Biomolecules, Inc. Product and process for introduction of a hinge region into a fusion protein to facilitate cleavage
US5091513A (en) 1987-05-21 1992-02-25 Creative Biomolecules, Inc. Biosynthetic antibody binding sites
US5132405A (en) 1987-05-21 1992-07-21 Creative Biomolecules, Inc. Biosynthetic antibody binding sites
US5258498A (en) 1987-05-21 1993-11-02 Creative Biomolecules, Inc. Polypeptide linkers for production of biosynthetic proteins
JPH02500329A (ja) 1987-05-21 1990-02-08 クリエイテイブ・バイオマリキユールズ・インコーポレーテツド ターゲット化多機能蛋白質
US4941880A (en) 1987-06-19 1990-07-17 Bioject, Inc. Pre-filled ampule and non-invasive hypodermic injection device assembly
US4790824A (en) 1987-06-19 1988-12-13 Bioject, Inc. Non-invasive hypodermic injection device
US5770701A (en) 1987-10-30 1998-06-23 American Cyanamid Company Process for preparing targeted forms of methyltrithio antitumor agents
US5606040A (en) 1987-10-30 1997-02-25 American Cyanamid Company Antitumor and antibacterial substituted disulfide derivatives prepared from compounds possessing a methyl-trithio group
FI903489A7 (fi) 1988-11-11 1990-07-10 Medical Res Council Yhden osan sisältävät ligandit, näitä ligandeja sisältävät reseptorit, menetelmiä niiden valmistamiseksi sekä ligandien ja reseptorien käytt ö
DE3920358A1 (de) 1989-06-22 1991-01-17 Behringwerke Ag Bispezifische und oligospezifische, mono- und oligovalente antikoerperkonstrukte, ihre herstellung und verwendung
CA2026147C (en) 1989-10-25 2006-02-07 Ravi J. Chari Cytotoxic agents comprising maytansinoids and their therapeutic use
US5208020A (en) 1989-10-25 1993-05-04 Immunogen Inc. Cytotoxic agents comprising maytansinoids and their therapeutic use
US5959177A (en) 1989-10-27 1999-09-28 The Scripps Research Institute Transgenic plants expressing assembled secretory antibodies
US5312335A (en) 1989-11-09 1994-05-17 Bioject Inc. Needleless hypodermic injection device
US5064413A (en) 1989-11-09 1991-11-12 Bioject, Inc. Needleless hypodermic injection device
US6075181A (en) 1990-01-12 2000-06-13 Abgenix, Inc. Human antibodies derived from immunized xenomice
US6150584A (en) 1990-01-12 2000-11-21 Abgenix, Inc. Human antibodies derived from immunized xenomice
US5770429A (en) 1990-08-29 1998-06-23 Genpharm International, Inc. Transgenic non-human animals capable of producing heterologous antibodies
DE69129154T2 (de) 1990-12-03 1998-08-20 Genentech, Inc., South San Francisco, Calif. Verfahren zur anreicherung von proteinvarianten mit geänderten bindungseigenschaften
US5571894A (en) 1991-02-05 1996-11-05 Ciba-Geigy Corporation Recombinant antibodies specific for a growth factor receptor
EP0590058B1 (en) 1991-06-14 2003-11-26 Genentech, Inc. HUMANIZED Heregulin ANTIBODy
GB9114948D0 (en) 1991-07-11 1991-08-28 Pfizer Ltd Process for preparing sertraline intermediates
EP0604580A1 (en) 1991-09-19 1994-07-06 Genentech, Inc. EXPRESSION IN E. COLI OF ANTIBODY FRAGMENTS HAVING AT LEAST A CYSTEINE PRESENT AS A FREE THIOL, USE FOR THE PRODUCTION OF BIFUNCTIONAL F(ab') 2? ANTIBODIES
FI941572L (fi) 1991-10-07 1994-05-27 Oncologix Inc Anti-erbB-2-monoklonaalisten vasta-aineiden yhdistelmä ja käyttömenetelmä
WO1993008829A1 (en) 1991-11-04 1993-05-13 The Regents Of The University Of California Compositions that mediate killing of hiv-infected cells
CA2372813A1 (en) 1992-02-06 1993-08-19 L.L. Houston Biosynthetic binding protein for cancer marker
US5383851A (en) 1992-07-24 1995-01-24 Bioject Inc. Needleless hypodermic injection device
ATE139900T1 (de) 1992-11-13 1996-07-15 Idec Pharma Corp Therapeutische verwendung von chimerischen und markierten antikörper gegen menschlichen b lymphozyt beschränkter differenzierung antigen für die behandlung von b-zell-lymphoma
US5635483A (en) 1992-12-03 1997-06-03 Arizona Board Of Regents Acting On Behalf Of Arizona State University Tumor inhibiting tetrapeptide bearing modified phenethyl amides
US5780588A (en) 1993-01-26 1998-07-14 Arizona Board Of Regents Elucidation and synthesis of selected pentapeptides
AU691811B2 (en) 1993-06-16 1998-05-28 Celltech Therapeutics Limited Antibodies
US5773001A (en) 1994-06-03 1998-06-30 American Cyanamid Company Conjugates of methyltrithio antitumor agents and intermediates for their synthesis
US5789199A (en) 1994-11-03 1998-08-04 Genentech, Inc. Process for bacterial production of polypeptides
US5731168A (en) 1995-03-01 1998-03-24 Genentech, Inc. Method for making heteromultimeric polypeptides
US5840523A (en) 1995-03-01 1998-11-24 Genetech, Inc. Methods and compositions for secretion of heterologous polypeptides
US5869046A (en) 1995-04-14 1999-02-09 Genentech, Inc. Altered polypeptides with increased half-life
US5712374A (en) 1995-06-07 1998-01-27 American Cyanamid Company Method for the preparation of substantiallly monomeric calicheamicin derivative/carrier conjugates
US5714586A (en) 1995-06-07 1998-02-03 American Cyanamid Company Methods for the preparation of monomeric calicheamicin derivative/carrier conjugates
US6410690B1 (en) 1995-06-07 2002-06-25 Medarex, Inc. Therapeutic compounds comprised of anti-Fc receptor antibodies
US6267958B1 (en) 1995-07-27 2001-07-31 Genentech, Inc. Protein formulation
GB9603256D0 (en) 1996-02-16 1996-04-17 Wellcome Found Antibodies
US5922845A (en) 1996-07-11 1999-07-13 Medarex, Inc. Therapeutic multispecific compounds comprised of anti-Fcα receptor antibodies
KR20000062345A (ko) 1996-12-26 2000-10-25 히라타 다다시 신규 폴리펩타이드, 신규 dna 및 신규 항체
US6171586B1 (en) 1997-06-13 2001-01-09 Genentech, Inc. Antibody formulation
JP2002506353A (ja) 1997-06-24 2002-02-26 ジェネンテック・インコーポレーテッド ガラクトシル化糖タンパク質の方法及び組成物
US6040498A (en) 1998-08-11 2000-03-21 North Caroline State University Genetically engineered duckweed
US20020012961A1 (en) 1999-04-15 2002-01-31 Genentech, Inc. Fibroblast growth factor- 19
CA2307166A1 (en) 1997-10-31 1999-05-14 Genentech, Inc. Methods and compositions comprising glycoprotein glycoforms
US6610833B1 (en) 1997-11-24 2003-08-26 The Institute For Human Genetics And Biochemistry Monoclonal human natural antibodies
EP1032668B1 (en) 1997-11-25 2008-05-28 Genentech, Inc. Fibroblast growth factor-19
WO1999029888A1 (en) 1997-12-05 1999-06-17 The Scripps Research Institute Humanization of murine antibody
US6194551B1 (en) 1998-04-02 2001-02-27 Genentech, Inc. Polypeptide variants
CA2323757C (en) 1998-04-02 2011-08-02 Genentech, Inc. Antibody variants and fragments thereof
JP4334141B2 (ja) 1998-04-20 2009-09-30 グリカート バイオテクノロジー アクチェンゲゼルシャフト 抗体依存性細胞傷害性を改善するための抗体のグリコシル化操作
HUP0104865A3 (en) 1999-01-15 2004-07-28 Genentech Inc Polypeptide variants with altered effector function
US6737056B1 (en) 1999-01-15 2004-05-18 Genentech, Inc. Polypeptide variants with altered effector function
EP2275540B1 (en) 1999-04-09 2016-03-23 Kyowa Hakko Kirin Co., Ltd. Method for controlling the activity of immunologically functional molecule
FR2796073B1 (fr) 1999-07-07 2003-08-29 Centre Nat Rech Scient Anticorps anti-idiotypiques des facteurs de croissance des fibroblastes et leur utilisation comme medicaments
JP2001072607A (ja) 1999-09-03 2001-03-21 Kyowa Hakko Kogyo Co Ltd 新規血管内皮機能改善法
CA2384089A1 (en) 1999-09-08 2001-03-15 Genentech, Inc. Fibroblast growth factor-19 (fgf-19) nucleic acids and polypeptides and methods of use for the treatment of obesity
EP1210426A2 (en) 1999-09-10 2002-06-05 Kyowa Hakko Kogyo Co., Ltd. Polymorphisms in a klotho gene
US7125978B1 (en) 1999-10-04 2006-10-24 Medicago Inc. Promoter for regulating expression of foreign genes
KR100797667B1 (ko) 1999-10-04 2008-01-23 메디카고 인코포레이티드 외래 유전자의 전사를 조절하는 방법
CA2388245C (en) 1999-10-19 2012-01-10 Kyowa Kirin Co., Ltd. The use of serum-free adapted rat cells for producing heterologous polypeptides
JP2003516755A (ja) 1999-12-15 2003-05-20 ジェネンテック・インコーポレーテッド ショットガン走査、すなわち機能性タンパク質エピトープをマッピングするための組み合わせ方法
AU767394C (en) 1999-12-29 2005-04-21 Immunogen, Inc. Cytotoxic agents comprising modified doxorubicins and daunorubicins and their therapeutic use
PT2857516T (pt) 2000-04-11 2017-08-28 Genentech Inc Anticorpos multivalentes e utilizações dos mesmos
KR100865801B1 (ko) 2000-08-29 2008-10-28 제넨테크, 인크. 암 치료의 효능을 증진시키는 방법
ATE453718T1 (de) 2000-08-29 2010-01-15 Genentech Inc Verfahren zur verbesserung von krebstherapie
US6946292B2 (en) 2000-10-06 2005-09-20 Kyowa Hakko Kogyo Co., Ltd. Cells producing antibody compositions with increased antibody dependent cytotoxic activity
US7064191B2 (en) 2000-10-06 2006-06-20 Kyowa Hakko Kogyo Co., Ltd. Process for purifying antibody
CN103333860B (zh) 2000-10-06 2015-07-08 协和发酵麒麟株式会社 产生抗体组合物的细胞
US6596541B2 (en) 2000-10-31 2003-07-22 Regeneron Pharmaceuticals, Inc. Methods of modifying eukaryotic cells
DE60131456T2 (de) 2000-11-30 2008-07-10 Medarex, Inc., Milpitas Transchromosomale transgen-nagetiere zur herstellung von humanen antikörpern
EP1423510A4 (en) 2001-08-03 2005-06-01 Glycart Biotechnology Ag ANTIBODY GLYCOSYLATION VARIANTS WITH INCREASED ANTIBODY-DEPENDENT CELLULAR CYTOTOXICITY
PL213948B1 (pl) 2001-10-25 2013-05-31 Genentech Inc Kompozycje zawierajace glikoproteine, czasteczka kwasu nukleinowego kodujaca te glikoproteine, komórka gospodarza, sposób wytwarzania glikoproteiny, kompozycja do zastosowania do leczenia, zastosowanie kompozycji i zestaw zawierajacy kompozycje
EP1327443A1 (en) 2001-12-21 2003-07-16 Kyowa Hakko Kogyo Co., Ltd. Therapeutic or preventing agent for the diseases caused by a decrease in the expression level of the klotho protein
US20040093621A1 (en) 2001-12-25 2004-05-13 Kyowa Hakko Kogyo Co., Ltd Antibody composition which specifically binds to CD20
ES2363765T3 (es) 2002-01-31 2011-08-16 MAX-PLANCK-Gesellschaft zur Förderung der Wissenschaften e.V. Agonistas de fgfr.
WO2003085102A1 (en) 2002-04-09 2003-10-16 Kyowa Hakko Kogyo Co., Ltd. Cell with depression or deletion of the activity of protein participating in gdp-fucose transport
EP1498491A4 (en) 2002-04-09 2006-12-13 Kyowa Hakko Kogyo Kk METHOD FOR INCREASING THE ACTIVITY OF AN ANTIBODY COMPOSITION FOR BINDING TO THE FC GAMMA RECEPTOR IIIA
KR20050000380A (ko) 2002-04-09 2005-01-03 교와 핫꼬 고교 가부시끼가이샤 게놈이 개변된 세포
CA2481920A1 (en) 2002-04-09 2003-10-16 Kyowa Hakko Kogyo Co., Ltd. Antibody composition-containing medicament
EP1498490A4 (en) 2002-04-09 2006-11-29 Kyowa Hakko Kogyo Kk PROCESS FOR PREPARING ANTIBODY COMPOSITION
WO2003084570A1 (en) 2002-04-09 2003-10-16 Kyowa Hakko Kogyo Co., Ltd. DRUG CONTAINING ANTIBODY COMPOSITION APPROPRIATE FOR PATIENT SUFFERING FROM FcϜRIIIa POLYMORPHISM
JP2003334088A (ja) 2002-05-22 2003-11-25 Pharma Design Inc ヒト由来の新規Klotho様タンパク質及びその遺伝子
EP1513879B1 (en) 2002-06-03 2018-08-22 Genentech, Inc. Synthetic antibody phage libraries
US20050282733A1 (en) 2002-06-27 2005-12-22 Prins Johannes B Differentiation modulating agents and uses therefor
US7361740B2 (en) 2002-10-15 2008-04-22 Pdl Biopharma, Inc. Alteration of FcRn binding affinities or serum half-lives of antibodies by mutagenesis
HUE035898T2 (en) 2002-12-16 2018-05-28 Genentech Inc Immunoglobulin variants and their applications
AU2004205631A1 (en) 2003-01-16 2004-08-05 Genentech, Inc. Synthetic antibody phage libraries
US7871607B2 (en) 2003-03-05 2011-01-18 Halozyme, Inc. Soluble glycosaminoglycanases and methods of preparing and using soluble glycosaminoglycanases
US20060104968A1 (en) 2003-03-05 2006-05-18 Halozyme, Inc. Soluble glycosaminoglycanases and methods of preparing and using soluble glycosaminogly ycanases
JPWO2005035586A1 (ja) 2003-10-08 2007-11-22 協和醗酵工業株式会社 融合蛋白質組成物
CA2542125A1 (en) 2003-10-09 2005-04-21 Kyowa Hakko Kogyo Co., Ltd. Process for producing antibody composition by using rna inhibiting the function of .alpha.1,6-fucosyltransferase
SI1680140T1 (sl) 2003-10-16 2011-08-31 Imclone Llc Inhibitorji receptorja-1 za fibroblastni rastni faktor in metode za zdravljenje z le-temi
HUE038955T2 (hu) 2003-11-05 2018-12-28 Roche Glycart Ag Antigén-kötõ molekulák fokozott Fc receptor-kötõ affinitással és effektor funkcióval
ES2605443T3 (es) 2003-11-06 2017-03-14 Seattle Genetics, Inc. Conjugados de auristatina con anticuerpos anti-HER2 o anti-CD22 y su uso en terapia
JPWO2005053742A1 (ja) 2003-12-04 2007-06-28 協和醗酵工業株式会社 抗体組成物を含有する医薬
WO2005066211A2 (en) 2003-12-19 2005-07-21 Five Prime Therapeutics, Inc. Fibroblast growth factor receptors 1, 2, 3, and 4 as targets for therapeutic intervention
CN1961003B (zh) 2004-03-31 2013-03-27 健泰科生物技术公司 人源化抗TGF-β抗体
US7785903B2 (en) 2004-04-09 2010-08-31 Genentech, Inc. Variable domain library and uses
WO2005100402A1 (en) 2004-04-13 2005-10-27 F.Hoffmann-La Roche Ag Anti-p-selectin antibodies
EP1789443A1 (en) 2004-09-02 2007-05-30 Eli Lilly And Company Muteins of fibroblast growth factor 21
TWI309240B (en) 2004-09-17 2009-05-01 Hoffmann La Roche Anti-ox40l antibodies
TR201808537T4 (tr) 2004-09-23 2018-07-23 Genentech Inc Sistein değiştirilmiş antikorlar ve konjugatlar.
JO3000B1 (ar) 2004-10-20 2016-09-05 Genentech Inc مركبات أجسام مضادة .
JP2006158339A (ja) 2004-12-09 2006-06-22 Kyoto Univ βKlotho遺伝子、Cyp7a1遺伝子、及びそれらの利用
JP2008522617A (ja) 2004-12-14 2008-07-03 イーライ リリー アンド カンパニー 線維芽細胞成長因子21の突然変異タンパク質
EP1957531B1 (en) 2005-11-07 2016-04-13 Genentech, Inc. Binding polypeptides with diversified and consensus vh/vl hypervariable sequences
WO2007064919A2 (en) 2005-12-02 2007-06-07 Genentech, Inc. Binding polypeptides with restricted diversity sequences
JP5209505B2 (ja) 2006-02-10 2013-06-12 ジェネンテック, インコーポレイテッド 抗fgf19抗体およびその使用方法
EP2016101A2 (en) 2006-05-09 2009-01-21 Genentech, Inc. Binding polypeptides with optimized scaffolds
US20080226635A1 (en) 2006-12-22 2008-09-18 Hans Koll Antibodies against insulin-like growth factor I receptor and uses thereof
TW201446265A (zh) 2007-04-02 2014-12-16 建南德克公司 克羅梭(klotho)beta調節劑之用途
US8697369B2 (en) 2007-04-06 2014-04-15 National Institute Of Advanced Industrial Science And Technology Method for screening a test substance for activating a receptor associated with FGF 21 activity
US7537903B2 (en) 2007-04-23 2009-05-26 Board Of Regents, The University Of Texas System FGF21 upregulates expression of GLUT-1 in a βklotho-dependent manner
CN100592373C (zh) 2007-05-25 2010-02-24 群康科技(深圳)有限公司 液晶显示面板驱动装置及其驱动方法
EP2188310B1 (en) 2007-08-03 2017-02-08 Genentech, Inc. Humanized anti-fgf19 antagonists and methods using same
EP3663318A1 (en) 2008-01-07 2020-06-10 Amgen Inc. Method for making antibody fc-heterodimeric molecules using electrostatic steering effects
NZ592009A (en) 2008-10-10 2012-11-30 Amgen Inc Fgf21 mutants and uses thereof
MX2012006397A (es) * 2009-12-02 2012-11-30 Amgen Inc PROTEINAS DE ENLACE QUE ENLAZAN A FGFR1C HUMANO, ß-KLOTHO HUMANA Y TANTO FGFR1C HUMANO COMO ß-KLOTHO HUMANA.
UA109888C2 (uk) 2009-12-07 2015-10-26 ІЗОЛЬОВАНЕ АНТИТІЛО АБО ЙОГО ФРАГМЕНТ, ЩО ЗВ'ЯЗУЄТЬСЯ З β-КЛОТО, РЕЦЕПТОРАМИ FGF І ЇХНІМИ КОМПЛЕКСАМИ
WO2011130417A2 (en) * 2010-04-15 2011-10-20 Amgen Inc. HUMAN FGF RECEPTOR AND β-KLOTHO BINDING PROTEINS
CN103415300B (zh) 2010-07-20 2018-02-23 诺沃—诺迪斯克有限公司 N‑末端修饰的fgf21化合物
WO2012158704A1 (en) 2011-05-16 2012-11-22 Genentech, Inc. Fgfr1 agonists and methods of use
US9574002B2 (en) 2011-06-06 2017-02-21 Amgen Inc. Human antigen binding proteins that bind to a complex comprising β-Klotho and an FGF receptor
TWI728373B (zh) 2013-12-23 2021-05-21 美商建南德克公司 抗體及使用方法
RS60593B1 (sr) 2014-01-24 2020-08-31 Ngm Biopharmaceuticals Inc Antitela koja vezuju domen 2 beta-kloto i postupci za njihovu upotrebu

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