JP5065529B2 - Opglへの抗体 - Google Patents
Opglへの抗体 Download PDFInfo
- Publication number
- JP5065529B2 JP5065529B2 JP2012006740A JP2012006740A JP5065529B2 JP 5065529 B2 JP5065529 B2 JP 5065529B2 JP 2012006740 A JP2012006740 A JP 2012006740A JP 2012006740 A JP2012006740 A JP 2012006740A JP 5065529 B2 JP5065529 B2 JP 5065529B2
- Authority
- JP
- Japan
- Prior art keywords
- certain embodiments
- antibody
- amino acid
- opgl
- αopgl
- 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.)
- Expired - Lifetime
Links
Images
Classifications
-
- 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
- C07K16/28—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
- C07K16/2866—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against receptors for cytokines, lymphokines, interferons
-
- 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
- C07K16/28—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
- C07K16/2875—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against the NGF/TNF superfamily, e.g. CD70, CD95L, CD153, CD154
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/44—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material not provided for elsewhere, e.g. haptens, metals, DNA, RNA, amino acids
-
- 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
- A61K39/39541—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum against materials from animals against normal tissues, cells
-
- 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
- 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
- A61K39/39558—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum against materials from animals against tumor tissues, cells, antigens
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
-
- 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
-
- 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
- A61P19/08—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
- A61P19/00—Drugs for skeletal disorders
- A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
- A61P19/10—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease for osteoporosis
-
- 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
- A61P3/12—Drugs for disorders of the metabolism for electrolyte homeostasis
- A61P3/14—Drugs for disorders of the metabolism for electrolyte homeostasis for calcium homeostasis
-
- 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
- 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
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/08—Plasma substitutes; Perfusion solutions; Dialytics or haemodialytics; Drugs for electrolytic or acid-base disorders, e.g. hypovolemic shock
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
-
- 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
-
- 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
- A61K2039/507—Comprising a combination of two or more separate 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
- C07K2317/50—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
- C07K2317/54—F(ab')2
-
- 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
- C07K2317/60—Immunoglobulins specific features characterized by non-natural combinations of immunoglobulin fragments
- C07K2317/62—Immunoglobulins specific features characterized by non-natural combinations of immunoglobulin fragments comprising only variable region components
- C07K2317/622—Single chain antibody (scFv)
-
- 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
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Immunology (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Molecular Biology (AREA)
- Physical Education & Sports Medicine (AREA)
- Biochemistry (AREA)
- Epidemiology (AREA)
- Genetics & Genomics (AREA)
- Biophysics (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Microbiology (AREA)
- Biomedical Technology (AREA)
- Rheumatology (AREA)
- Mycology (AREA)
- Hematology (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Endocrinology (AREA)
- Diabetes (AREA)
- Urology & Nephrology (AREA)
- Obesity (AREA)
- General Physics & Mathematics (AREA)
- Oncology (AREA)
- Biotechnology (AREA)
- Cell Biology (AREA)
- Pain & Pain Management (AREA)
- Food Science & Technology (AREA)
- Physics & Mathematics (AREA)
Description
組換えDNA、オリグヌクレオチド合成並びに組織培養および形質転換(例えば、電気穿孔法、リポ移入)用の標準的技術を用いることができる。酵素的反応および精製技術を、製造者の仕様に従って、または当分野で一般的に行われるように、もしくはここで記載のように行うことができる。前記技術および手順は、通常、当分野で良く知られている従来法に従って、また、本明細書全体において引用および記載されている種々の一般的およびより具体的な引例に記載のように行うことができる。例えば、Sambrookら著、Molecular Cloning:A Laboratory Manual(第2版、Cold Spring Harbor Laboratory Press、Cold Spring Harbor、N.Y.(1989年))が参照され、ここで任意の目的のために参考として取り込まれる。特定の定義が無い限り、分析化学、合成有機化学および医学および薬学的化学に関して利用される命名法およびその実験室的手順および技術は、当分野においてよく知られていると共に一般的に用いられるものである。化学的合成、化学的分析、薬学的調製、処方、および送達、および患者の治療用の標準的技術を用いてよい。
ここで用いられる「単離ポリヌクレオチド」という用語は、ゲノム、cDNA、または合成起源またはそれらの組み合わせのポリヌクレオチドを意味し、その起源に依り、その「単離ポリヌクレオチド」は、(1)「単離ポリヌクレオチド」が天然に見られるポリヌクレオチドの全体または一部を伴わず、(2)天然には結合していないポリヌクレオチドに結合している、または(3)より大きな配列の一部として天然に存在しない。
アルゴリズム:Needlemanら著、J.Mol.Biol.、第48巻:443〜453頁(1970年);
比較マトリクス:Henikoffら著、前掲書(1992年)からのBLOSUM62
ギャップ・ペナルティ:12
ギャップ・レングス・ペナルティ:4
類似性の閾値:0
2)中性親水性:Cys、Ser、Thr、Asn、Gln;
3)酸性:Asp、Glu;
4)塩基性:His、Lys、Arg;
5)鎖方向付けに影響する残基:Gly、Pro;および
6)芳香族:Trp、Tyr、Phe。
天然に存在する抗体の構造単位は、典型的に、四量体を含む。各々のそのようなテトラマーは、典型的に、二つの同一対のポリペプチド鎖を含み、各対は一つの全長L鎖(ある実施形態において、約25kDa)と一つの全長H鎖(ある実施形態において、約50kDaから70kDa)を有する。各鎖のアミノ末端部分は、典型的に抗原認識を担当する約100〜110またはそれ以上のアミノ酸の可変領域を典型的に含む。各鎖のカルボキシ末端部分は、エフェクター機能を担当し得る定常領域を典型的に規定する。ヒトL鎖は、典型的に、κおよびλL鎖とに分類される。H鎖は、典型的に、μ、δ、γ、αまたはεと分類され、それぞれIgM、IgD、IgG、IgAおよびIgEとして抗体アイソタイプを定義する。IgGは、IgG1、IgG2、IgG3およびIgG4を含む幾つかのサブクラスを有するが、これらに制限されない。IgMは、IgM1およびIgM2を含むサブクラスを有するが、これらに限定されない。IgAは同様にIgA1およびIgA2を含むサブクラスに下位分割されるが、これらに限定されない。全長L鎖およびH鎖中では、典型的に、可変領域と定常領域が、約12以上のアミノ酸からなる「J」領域により連結され、H鎖は、約10以上のアミノ酸からなる「D」領域も含む。例えば、Fundamental Immunology 第7章(Paul,W.編、第2版、Raven Press、N.Y.(1989年))を参照されたい(全ての目的のために、その全体を参考のために取り入れる)。各L/H鎖対からなる可変領域は、典型的に、抗原結合部位を形成する。
二重特異的または二重機能的抗体は、典型的には、二つの異なるH/L鎖対と二つの異なる結合部位を有する人工的ハイブリッド抗体である。二重特異的抗体は、限定はされないがハイブリドーマの融合またはFab’断片の結合を含む種々の方法により製造することができる。例えば、Songsivilai & Lachmann Clin.Exp.Immunol.第79巻:315〜321頁(1990年)、Kostelnyら著、J.Immunol.第148巻:1547〜1553頁(1992年)を参照のこと。
ある実施形態によれば、OPGLに特異的に結合する特定の抗体が本発明に含まれる。ある実施形態において、全長OPGL、OPGLの可溶性形態、またはその断片を用いて免疫化することにより抗体を製造することができる。ある実施形態において、本発明の抗体はポリクローナルまたはモノクローナル、および/または組換え抗体であってよい。ある実施形態において、本発明の抗体は、例えば、ヒト型抗体を生成することができるトランスジェニック動物の免疫化により調製されるヒト型抗体である(例えば、PCT公開出願番号WO93/12227参照)。
骨粗鬆症、例えば、原発性骨粗鬆症、内分泌性骨粗鬆症(甲状腺機能亢進症、副甲状腺機能亢進症、クッシング症候群および先端巨大症が挙げられるがこれらに限定されない)、骨粗鬆症の遺伝性および先天性型(骨形成不全症、ホモシスチン尿症、メンケズ症候群、ライリー−ダイ症候群が挙げられるがこれらに限定されない)、および端部の不動化による骨粗鬆症(これらに限定されない);
成人および若年者における骨のページェット病(変性性骨炎);
骨髄炎、すなわち、骨損失につながる、骨における感染性病変;
高カルシウム血症、例えば、充実性腫瘍(乳、肺および腎臓を含むがこれらに限定されない)および血液悪性病変(多発性骨髄腫、リンパ腫および白血病を含むがこれらに限定されない)から生じる高カルシウム血症、特発性高カルシウム血症、および甲状腺機能亢進症および腎機能障害に関わる高カルシウム血症(これらに限定されない);
骨減少症、例えば、手術に続く骨減少症、ステロイド投与により誘発される骨減少症、小腸および大腸の疾患に関わる骨減少症、および慢性肝臓および腎臓疾患に関わる骨減少症(これらに限定されない);
骨壊死、すなわち、骨細胞死であって、外傷に関わる骨壊死、ゴーシェ病に関わる骨壊死、鎌状赤血球貧血に関わる骨壊死、全身性エリテマトーデスに関わる骨壊死、リューマチ性関節炎に関わる骨壊死、歯周病に関わる骨壊死、骨溶解性転移に関わる骨壊死、および他の症状に関わる骨壊死(これらに限定されない);および
リューマチ性関節炎に関わる軟骨の損失および関節侵食。
全長ヒトOPGL cDNAを発現するCHO細胞を用いて、ヒトイムノグルブリン遺伝子を含むトランスジェニックマウスを免疫する。免疫されたマウスからのリンパ説をネズミ骨髄腫細胞に融合させてハイブリドーマを発生させる。ハイブリドーマ系統からの上澄みを、ヒトOPGLと反応する抗体についてELISAアッセイにおいて試験する。抗OPGL発現ハイブリドーマ系統AMG6.5、AMG6.4およびAMG6.1は、OPGLに対する高い親和性を有する抗体を発現することがわかり(Kdがそれぞれ0.28nM、0.29nMおよび0.23nM)、AMG6.5をクローニングのために選択する。AMG6.5およびAMG6.4からのH鎖およびL鎖cDNAクローンは同一であり、AMG6.5を用いて、αOPGL−1 L鎖cDNAをクローン化し、AMG6.4を用いて、αOPGL−1 H鎖cDNAをクローン化する。
AMG6.5全RNA調製される第1のストランドcDNAから、PCR増幅方法を用いて、αOPGL−1κL鎖可変領域を得る。第1のストランドcDNAは、拡張5’−アダプタ(5’−GGCCGGATAGGCCTCACNNNNNNT−3’(配列番号15)を有するランダムプライマーおよび材料を用い、Gibco SuperScript II(登録商標)Preamplification System for First Strand cDNA Synthesis kit(カタログ番号18089−011)により提供される方法を使用して、AMG6.5全RNAから調製する。PCRには以下のオリゴヌクレオチドを用いる:
5’κRACEプライマー:
5’−GAT GAC CCA GTC TCC AGC CAC CCT G−3’(配列番号5)
3’κRACEプライマー:
5’−AAG GGT CAG AGG CCA AAG GAT GG−3’(配列番号6)
αOPGL−1 IgG2 H鎖を、Clontech Marathon(登録商標)cDNA Amplification Kit(カタログ番号K1802−1)を用いて作成したAMG6.4ハイブリドーマ二本鎖cDNAからクローニングする。AMG6.4H鎖cDNAの増幅は、ヒト生殖細胞系IgG2 H鎖定常領域即位的プライマー(図示せず)およびRACEプライマーおよび他の材料ならびにMarathon(登録商標)cDNA増幅キットで提供される方法を用いて行われるcDNA末端(RACE)技術の5’および3’迅速増幅により達成される。
5’−GGC ACG GTC ACC ACG CTG CTG AG−3’(配列番号9)
3’−IgG2 RACEプライマー
5’−CCT CCA CCA AGG GCC CAT TGG TCT−3’(配列番号10)
αOPGL−1抗体の安定発現を、ジヒドロフォレートリダクターゼ欠損(DHFR−)チャイニーズハムスター卵巣細胞(CHO AM−1/D、米国特許第6,210,924号)中へのαOPGL−1−κ/pDSRα19およびαOPGL−1−IgG2/pDSRα19プラスミドの共形質移入およびその後の個々のクローンの単離および試験により達成する。
細胞系125Qの調製および形成
αOPGL−1を生成するCHO細胞を、血清非含有条件下に96ウエルプレート中で2回限界希釈することによりクローニングする。クローンを、種々の懸濁容器中での生成および成長特性に基づいて選択する。EIAを行って、最高水準のαOPGL−1を生成するクローンを選択する。次に、倍加時間および密度を含む成長特性を、100ml、250ml、500ml、1L、および3Lのスピナフラスコ中、および3LのAplikon生物反応容器中でクローンを成長させることにより測定する。培地中で最高密度を達成する倍加時間が最も速いクローンを選択し、Cell Line 125Qとする。クローンが拡張して、約1×107cells/mLで360個のアンプルを凍結するのに充分な細胞を作成し、細胞を低温保存用の血清非含有培地(10ml/L可欠アミノ酸および10ml/L L−グルタミン(Gibco/LTI/Invitrogen)を付加した90% VM−Soy Batch Medium(詳細は表3を参照)、および10%ジメチルスルホキシド(JT Baker))中に再懸濁し凍結する。アンプルを、接触制限装置中に貯蔵し、液体窒素デューア瓶中の液体窒素に漬ける。
αOPGL−1−κ/pDSRα19およびαOPGL−1−IgG2/pDSRα19からαOPGL−1を発現するCHO細胞のクローン系であるCell Line125Q中で発現することによりαOPGL−1を生産する。αOPGL−1用の細胞培養プロセスを図19に示す。各生産ランについて、Cell Line125Qのバイアルからの細胞を、先ず、125mlエルレンマイエルシェーカー中で10ml/L非必須アミノ酸と10ml/L L−グルタミン(Gibco/LTI/Invitrogen)(VM−Soy Supp)を補足したVM−Soy Batch Medium(組成については表3を参照)50ml中で100rpmで5日間成長させる。次に、培地全体を用いて500mlスピナフラスコ中のVM−Soy Suppに接種して3×105バイアル細胞/ml(3E5 vc/ml)とし、70rpmで3日から4日間回転させつつ成長させる。次に、500mlスピナフラスコからの培地全体を用いて、3Lスピナフラスコ中のVM−Soy Suppに接種して3E5 vc/mlとし、70rpmで3日から4日間回転させつつ成長させる。
全細胞培養プロセスを通して用いるための細胞培養培地は、Dulbecco’s Modified Eagle’s Medium/Ham’s Nutrient F12(DMEM/F12、1:1)に基づき、補足水準のアミノ酸、さらなる栄養および塩、大豆加水分解物および組換えヒトインスリン(Nucellin(登録商標)Zn、Eli Lilly)を含む。成分を表3に列挙する。この培地をVM−Soyと呼ぶ。培地溶液を、使用前に0.2μm孔寸法の薄膜フィルターを通して濾過する。
CHO細胞中に発現されたαOPGL−1は、細胞外培地中に分泌される。一連の工程を用いて純粋な物質を生産することができる。このプロセスは、疎水性電荷誘導、カチオン交換、および低pH工程およびバイアルフィルターを用いる疎水性相互作用クロマトグラフィーを用いる。これらの手順を以下に記載する。
このクロマトグラフィー工程は、大部分の宿主細胞蛋白およびDNAを除去する。濃縮培養上清(CCM)を、Cuno 30SPフィルター、次にCuno VR07荷電セルロース系フィルターを通して濾過し、次に、MEPHyperCel樹脂上に乗せる。負荷後、カラムを、平衡緩衝液(20mM Tris pH7.2)で洗う。抗体を、低pH緩衝液(20mM酢酸ナトリウム、pH5.0)を用いて樹脂から溶離する。カラムから溶離されると、生産物を、カラム溶出液の280nmでの吸収に基づいて集める。
MEPプールを、pH3.7まで滴定し、約60分間保持して汚染の可能性あるレトロウイルスを不活化する。保持工程に続いて、pHを約6.0に調節する。
pH調節したプールを、Millipore Viresolve NFRフィルターまたは同等物を通して濾過する。抗体がフィルターを通過し、汚染可能性ウイルス50nmより大は維持される。
抗体を、SP Sepharose HP(Amersham Pharmacia)または同等物を用いるカチオン交換クロマトグラフィーによりさらに精製する。カチオン交換クロマトグラフィー工程は、さらなるCHO細胞蛋白、DNA、低分子量蛋白、およびαOPGL−1の凝集形状を除去する。ウイルス濾過プールを、カチオン交換樹脂上に負荷する。負荷後、カラムを平衡緩衝液(20mM NaMES pH6.2)で洗う。次に、抗体を、塩が増加するリニアグラジエント(20mM NaMES pH6.2、0M NaCl〜20mM NaMES pH6.2、0.3M NaCl)で溶離する。カラムから溶離すると、カラム溶出液の280nmでの吸収に基づき生産物を集める。
抗体は、Phenyl Toyopearl 650S(Tosoh Biosep)または同等物を用いる疎水性相互作用クロマトグラフィーによりさらに精製される。疎水性相互作用クロマトグラフィー工程は、仕上げ工程として用いられ、さらなるCHO細胞蛋白、DNA、低分子量蛋白および、αOPGL−1の凝集形を除去する。カチオン交換プールを条件付けしてから、15℃から25℃で硫酸アンモニウムを添加して105mS/cmを超える導電性にすることによりカラムに負荷する。負荷後、カラムを平衡緩衝液(1M 燐酸カリウム pH8)で洗う。次に、抗体を、塩濃度が減少するリニアグラジエント(1M燐酸カリウム、0mM Tris pH8〜0M燐酸カリウム、20mM Tris pH8)で溶離する。カラムから溶離すると、カラム溶出液の280nmでの吸収に基づき生成物を集める。
HICカラムプールを濃縮し、50kD NMWL薄膜(Millipore Biomax 50)を用いて接線フロー限外濾過により製剤緩衝液中にダイアフィルトレーションする。製剤緩衝席は、10mM酢酸塩、5%ソルビトール、pH5.2およびαOPGL−1を30mg/mLで含む。
精製されたバルクを、0.22μm PVDFフィルター(Millipore)を通し、サンプルを得、固定冷凍器において約−30℃で貯蔵する。
実施例1および2に記載のように二つの発現ベクターを形質移入したCHO細胞中において生産された抗体を、以下の実施例4、5および6において用いることができる。
破骨細胞形成の阻害
RAW264.7(ATCC No.TIB−71、Manassas、VA)は、Abelsonネズミ白血病ウイルス誘発腫瘍から誘導されたネズミマクロファージ細胞系である。RAW264.7細胞は、OPGLの存在下に、破骨細胞様細胞に分化する。OPGLの存在下におけるRAW細胞からの培養中の破骨細胞の生成についての基本的アッセイが、Simonetら著(1997年)Cell第89巻、309頁およびLaceyら著(1998年)Cell第93巻、165頁に詳細に記載されており、これを任意の目的のために参照してここに組み込まれる。
αOPGL−1の性能を、OPGリガンドの、その同族受容体である、破骨細胞分化および活性化受容体(ODAR、RNAKとしても知られている)への結合を阻害する性能により示す。このアッセイは、均質時間分解蛍光共鳴(HTRF)を用いて、ユーロピウム結合オステオプロテゲリンリガンド(Eu−OPGL)へのαOPGL−1の結合を検出する。αOPGL−1が、ODARへのEu−OPGLの結合を阻害すると、蛍光出力は減少し、存在するαOPGL−1の量は、蛍光量と逆相関する。
4.5歳以下で2kgから4kgの6匹の雄および6匹の雌のカニクイザルを、四つの投与群に割り当てる。第1群は3匹の雄と3匹の雌からなる。第2、第3および第4群は、各々、1匹の雄と1匹の雌からなる。第1群の動物は、1mg/kg αOPGL−1の単一SC投与量を投与し、第2、第3および第4群の動物は、それぞれ0.1、1.0または10.0mg/kg αOPGL−1の単一IV投与量を投与する。
Claims (9)
- H鎖は配列番号2の20〜467アミノ酸残基で表されるアミノ酸配列を含み、L鎖は配列番号4の21〜235アミノ酸残基で表されるアミノ酸配列を含む、H鎖およびL鎖を含む抗体であって、OPGLがODARに結合することにより誘導される破骨細胞の分化を抑制する抗体。
- H鎖は配列番号2の20〜467アミノ酸残基で表されるアミノ酸配列からなり、L鎖は配列番号4の21〜235アミノ酸残基で表されるアミノ酸配列からなる、H鎖およびL鎖を含む抗体であって、OPGLがODARに結合することにより誘導される破骨細胞の分化を抑制する抗体。
- (a)H鎖は、配列番号2の20〜467残基で表されるアミノ酸配列に少なくとも99%の同一性を有する配列を含み、
(b)L鎖は、配列番号4の21〜235残基で表されるアミノ酸配列に少なくとも99%の同一性を有する配列を含み、および
(c)抗体がオステオプロテゲリンリガンド(OPGL)と相互反応する、
H鎖及びL鎖を含む抗体。 - 請求項1〜3のいずれかに記載の抗体を含む、患者の骨損失を治療するための組成物であって、該骨損失が骨粗鬆症、ページェット病、骨髄炎、高カルシウム血症、骨減少症、骨壊死、並びにリューマチ関節炎に関わる関節侵食及び軟骨損失に関わるものである組成物。
- 請求項1〜3のいずれかに記載の抗体を含む、患者の骨損失を伴う炎症性症状を治療する組成物。
- 請求項1〜3のいずれかに記載の抗体を含む、患者の骨損失を伴う自己免疫症状を治療する組成物。
- 癌に関わる骨損失を治療するための、請求項1〜3のいずれかに記載の抗体を含む組成物。
- 癌が乳癌、前立腺癌、甲状腺癌、腎臓癌、肺癌、直腸癌、膀胱癌、子宮頸部癌、卵巣癌、肝臓癌、及び胃腸管の癌から選択される請求項7に記載の組成物。
- 癌が多発性骨髄腫及びリンパ腫から選択される請求項7に記載の組成物。
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US30117201P | 2001-06-26 | 2001-06-26 | |
US60/301,172 | 2001-06-26 |
Related Parent Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2009161406A Division JP4927910B2 (ja) | 2001-06-26 | 2009-07-08 | Opglへの抗体 |
Related Child Applications (2)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2012066632A Division JP2012153701A (ja) | 2001-06-26 | 2012-03-23 | Opglへの抗体 |
JP2012148656A Division JP5576903B2 (ja) | 2001-06-26 | 2012-07-02 | Opglへの抗体 |
Publications (2)
Publication Number | Publication Date |
---|---|
JP2012140430A JP2012140430A (ja) | 2012-07-26 |
JP5065529B2 true JP5065529B2 (ja) | 2012-11-07 |
Family
ID=23162250
Family Applications (13)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2003509075A Expired - Lifetime JP4212470B2 (ja) | 2001-06-26 | 2002-06-25 | Opglへの抗体 |
JP2008175541A Expired - Lifetime JP4358282B2 (ja) | 2001-06-26 | 2008-07-04 | Opglへの抗体 |
JP2009161406A Expired - Lifetime JP4927910B2 (ja) | 2001-06-26 | 2009-07-08 | Opglへの抗体 |
JP2012006740A Expired - Lifetime JP5065529B2 (ja) | 2001-06-26 | 2012-01-17 | Opglへの抗体 |
JP2012066632A Withdrawn JP2012153701A (ja) | 2001-06-26 | 2012-03-23 | Opglへの抗体 |
JP2012148656A Expired - Lifetime JP5576903B2 (ja) | 2001-06-26 | 2012-07-02 | Opglへの抗体 |
JP2014218929A Pending JP2015057408A (ja) | 2001-06-26 | 2014-10-28 | Opglへの抗体 |
JP2014239576A Pending JP2015078205A (ja) | 2001-06-26 | 2014-11-27 | Opglへの抗体 |
JP2016113389A Pending JP2016216464A (ja) | 2001-06-26 | 2016-06-07 | Opglへの抗体 |
JP2017247287A Ceased JP2018154614A (ja) | 2001-06-26 | 2017-12-25 | Opglへの抗体 |
JP2019107837A Pending JP2019214563A (ja) | 2001-06-26 | 2019-06-10 | Opglへの抗体 |
JP2019232389A Pending JP2020073518A (ja) | 2001-06-26 | 2019-12-24 | Opglへの抗体 |
JP2021128771A Pending JP2022000424A (ja) | 2001-06-26 | 2021-08-05 | Opglへの抗体 |
Family Applications Before (3)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2003509075A Expired - Lifetime JP4212470B2 (ja) | 2001-06-26 | 2002-06-25 | Opglへの抗体 |
JP2008175541A Expired - Lifetime JP4358282B2 (ja) | 2001-06-26 | 2008-07-04 | Opglへの抗体 |
JP2009161406A Expired - Lifetime JP4927910B2 (ja) | 2001-06-26 | 2009-07-08 | Opglへの抗体 |
Family Applications After (9)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2012066632A Withdrawn JP2012153701A (ja) | 2001-06-26 | 2012-03-23 | Opglへの抗体 |
JP2012148656A Expired - Lifetime JP5576903B2 (ja) | 2001-06-26 | 2012-07-02 | Opglへの抗体 |
JP2014218929A Pending JP2015057408A (ja) | 2001-06-26 | 2014-10-28 | Opglへの抗体 |
JP2014239576A Pending JP2015078205A (ja) | 2001-06-26 | 2014-11-27 | Opglへの抗体 |
JP2016113389A Pending JP2016216464A (ja) | 2001-06-26 | 2016-06-07 | Opglへの抗体 |
JP2017247287A Ceased JP2018154614A (ja) | 2001-06-26 | 2017-12-25 | Opglへの抗体 |
JP2019107837A Pending JP2019214563A (ja) | 2001-06-26 | 2019-06-10 | Opglへの抗体 |
JP2019232389A Pending JP2020073518A (ja) | 2001-06-26 | 2019-12-24 | Opglへの抗体 |
JP2021128771A Pending JP2022000424A (ja) | 2001-06-26 | 2021-08-05 | Opglへの抗体 |
Country Status (33)
Country | Link |
---|---|
US (8) | US7364736B2 (ja) |
EP (5) | EP2270052B8 (ja) |
JP (13) | JP4212470B2 (ja) |
KR (2) | KR20040023630A (ja) |
CN (2) | CN103232539B (ja) |
AR (1) | AR034637A1 (ja) |
AT (1) | ATE464068T1 (ja) |
AU (2) | AU2002320157C1 (ja) |
BR (1) | BRPI0210579B8 (ja) |
CA (1) | CA2451955C (ja) |
CY (5) | CY1110196T1 (ja) |
DE (2) | DE60235989D1 (ja) |
DK (4) | DK1409016T4 (ja) |
EA (1) | EA021242B9 (ja) |
ES (5) | ES2342820T5 (ja) |
FR (1) | FR10C0050I2 (ja) |
HK (1) | HK1187932A1 (ja) |
IL (3) | IL159512A0 (ja) |
LU (1) | LU91757I2 (ja) |
ME (2) | MEP32608A (ja) |
MX (1) | MXPA04000134A (ja) |
MY (1) | MY143582A (ja) |
NO (5) | NO345566B1 (ja) |
NZ (4) | NZ530765A (ja) |
PL (1) | PL222211B1 (ja) |
PT (4) | PT2087908T (ja) |
RS (1) | RS54274B1 (ja) |
SG (3) | SG2011076551A (ja) |
TR (3) | TR201900581T4 (ja) |
TW (2) | TWI326285B (ja) |
WO (1) | WO2003002713A2 (ja) |
YU (1) | YU103003A (ja) |
ZA (1) | ZA200400521B (ja) |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2018154614A (ja) * | 2001-06-26 | 2018-10-04 | アムジェン フレモント インク. | Opglへの抗体 |
Families Citing this family (199)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
IL117175A (en) * | 1995-02-20 | 2005-11-20 | Sankyo Co | Osteoclastogenesis inhibitory factor protein |
EP2003203A1 (en) * | 1996-12-23 | 2008-12-17 | Immunex Corporation | Ligand for receptor activator of nf-kappa b, ligand is member of TNF superfamily |
HU229841B1 (en) | 1997-04-15 | 2014-09-29 | Daiichi Sankyo Co Ltd | Antibodies against obm |
WO1998046751A1 (en) | 1997-04-16 | 1998-10-22 | Amgen Inc. | Osteoprotegerin binding proteins and receptors |
US6316408B1 (en) | 1997-04-16 | 2001-11-13 | Amgen Inc. | Methods of use for osetoprotegerin binding protein receptors |
ATE517916T1 (de) | 1998-05-14 | 2011-08-15 | Immunex Corp | Verfahren zur hemmung der wirkung der osteoklasten |
US20030103978A1 (en) * | 2000-02-23 | 2003-06-05 | Amgen Inc. | Selective binding agents of osteoprotegerin binding protein |
AU9303001A (en) | 2000-09-22 | 2002-04-02 | Immunex Corp | Screening assays for agonists or antagonists of receptor activat or of nf-kb |
AR032028A1 (es) | 2001-01-05 | 2003-10-22 | Pfizer | Anticuerpos contra el receptor del factor de crecimiento similar a insulina |
PL375041A1 (en) | 2002-04-05 | 2005-11-14 | Amgen Inc. | Human anti-opgl neutralizing antibodies as selective opgl pathway inhibitors |
ES2558303T3 (es) | 2002-09-11 | 2016-02-03 | Chugai Seiyaku Kabushiki Kaisha | Método de purificación de proteínas |
EP1479695B1 (en) * | 2003-05-14 | 2010-02-17 | Kenta Biotech AG | Human monoclonal antibody specific for lipopolysaccharides (LPS) of serotype IATS O6 of Pseudomonas aeruginosa |
US7318925B2 (en) * | 2003-08-08 | 2008-01-15 | Amgen Fremont, Inc. | Methods of use for antibodies against parathyroid hormone |
ATE420660T1 (de) | 2003-08-08 | 2009-01-15 | Amgen Fremont Inc | Antikörper gegen parath-hormon (pth) und ihre verwendungen |
US7820800B2 (en) * | 2003-11-05 | 2010-10-26 | Ares Trading S.A. | Process for the purification of IL-18 binding protein |
TWI359026B (en) * | 2004-02-12 | 2012-03-01 | Sankyo Co | Pharmaceutical composition for the osteoclast rela |
WO2006015373A2 (en) | 2004-08-04 | 2006-02-09 | Amgen Inc | Antibodies to dkk-1 |
WO2006047380A2 (en) * | 2004-10-22 | 2006-05-04 | Amgen, Inc. | Method and media for single cell serum-fee culture of cho cells |
TW200714289A (en) * | 2005-02-28 | 2007-04-16 | Genentech Inc | Treatment of bone disorders |
MX2007012499A (es) * | 2005-04-11 | 2007-12-06 | Medarex Inc | Purificacion de proteinas. |
ES2776657T3 (es) * | 2005-06-14 | 2020-07-31 | Amgen Inc | Formulaciones de proteínas autotamponantes |
AU2015242973C1 (en) * | 2005-06-14 | 2018-07-05 | Amgen Inc. | Self-buffering protein formulations |
WO2007016562A2 (en) * | 2005-07-29 | 2007-02-08 | Amgen Inc. | Formulations that inhibit protein aggregation |
AR056806A1 (es) * | 2005-11-14 | 2007-10-24 | Amgen Inc | Moleculas quimericas de anticuerpo rankl- pth/ pthrp |
US7989160B2 (en) | 2006-02-13 | 2011-08-02 | Alethia Biotherapeutics Inc. | Polynucleotides and polypeptide sequences involved in the process of bone remodeling |
US8168181B2 (en) | 2006-02-13 | 2012-05-01 | Alethia Biotherapeutics, Inc. | Methods of impairing osteoclast differentiation using antibodies that bind siglec-15 |
JP4881946B2 (ja) * | 2006-04-28 | 2012-02-22 | 共立製薬株式会社 | 動物由来蛋白なしで培養可能な猫の細胞、これを用いたウイルスの生産方法、及びワクチンの生産方法 |
US8513393B2 (en) | 2006-08-28 | 2013-08-20 | Ares Trading S.A. | Process for the purification of Fc-containing proteins |
BRPI0809112A2 (pt) * | 2007-03-22 | 2014-08-26 | Imclone Llc | Formulações estáveis de anticorpos |
CN104231082B (zh) | 2007-05-24 | 2018-12-21 | 埃博灵克斯股份有限公司 | 用于治疗骨疾病和病症的针对rank-l的氨基酸序列以及包括其的多肽 |
CL2008002444A1 (es) | 2007-08-21 | 2009-09-04 | Amgen Inc | Anticuerpo o fragmento del mismo que se une a la proteina c-fms humana; molecula de acido nucleico que la codifica; vector y celula huesped; metodo de elaboracion; composicion farmaceutica que la comprende; y su uso para tratar o prevenir una condicion asociada con c-fms en un paciente. |
AU2008298904B2 (en) * | 2007-09-14 | 2014-10-16 | Amgen Inc. | Homogeneous antibody populations |
EP2205280B1 (en) | 2007-09-27 | 2019-09-04 | Amgen Inc. | Pharmaceutical formulations |
WO2009048072A1 (ja) | 2007-10-11 | 2009-04-16 | Daiichi Sankyo Company, Limited | 破骨細胞関連蛋白質Siglec-15を標的とした抗体 |
WO2009064838A1 (en) | 2007-11-15 | 2009-05-22 | Amgen, Inc. | Aqueous formulation of erythropoiesis stimulating protein stablised by antioxidants for parenteral administration |
US8883146B2 (en) | 2007-11-30 | 2014-11-11 | Abbvie Inc. | Protein formulations and methods of making same |
US8637312B2 (en) | 2008-01-09 | 2014-01-28 | Cellca Gmbh | Mammalian culture media with polyamine and iron |
CN103720587A (zh) * | 2008-02-07 | 2014-04-16 | 安姆根有限公司 | 稳定化的蛋白组合物 |
CL2009001735A1 (es) * | 2008-08-19 | 2010-02-19 | Regeneron Pharma | Anticuerpo humano o fragmento de union a antigeno del mismo que une e inhibe actividad de ligando del activador del receptor de nf-kb (rankl); adn codificante; vector de expresion; metodo para producir dicho anticuerpo; composicion farmaceutica que lo comprende; uso para atenuar o inhibir enfermedad o condicion mediada por rankl |
CA2753287A1 (en) | 2009-02-24 | 2010-09-02 | Glaxo Group Limited | Antigen-binding constructs |
CA2753332A1 (en) | 2009-02-24 | 2010-09-02 | Glaxo Group Limited | Antigen-binding constructs |
CA2753263A1 (en) | 2009-02-24 | 2010-09-02 | Glaxo Group Limited | Multivalent and/or multispecific rankl-binding constructs |
US8575316B2 (en) | 2009-04-09 | 2013-11-05 | Daiichi Sankyo Company, Limited | Anti-Siglec-15 antibody |
US9662271B2 (en) | 2009-10-23 | 2017-05-30 | Amgen Inc. | Vial adapter and system |
PT3564357T (pt) | 2010-02-01 | 2022-06-14 | Rebiotix Inc | Bacterioterapia para colite por clostridium difficile |
EA032537B1 (ru) | 2010-06-07 | 2019-06-28 | Эмджен Инк. | Способ работы устройства для доставки лекарственного средства |
JP5699030B2 (ja) * | 2010-07-05 | 2015-04-08 | Axis株式会社 | エタネルセプトを含む線維筋痛症の治療剤 |
RU2013119983A (ru) | 2010-10-05 | 2014-11-20 | Дайити Санкио Компани, Лимитед | Антитело, направленное на связанный с остеокластами белок сиглек-15 |
US10047398B2 (en) | 2010-10-06 | 2018-08-14 | Fundacio Institut De Recerca Biomedica (Irb Barcelona) | Method for the diagnosis, prognosis and treatment of breast cancer metastasis |
WO2012135315A1 (en) | 2011-03-31 | 2012-10-04 | Amgen Inc. | Vial adapter and system |
LT2699293T (lt) | 2011-04-20 | 2019-04-25 | Amgen Inc. | Automatinio purškimo prietaisas |
EP2702077A2 (en) | 2011-04-27 | 2014-03-05 | AbbVie Inc. | Methods for controlling the galactosylation profile of recombinantly-expressed proteins |
AU2012264809B2 (en) | 2011-05-27 | 2017-05-04 | Ablynx Nv | Inhibition of bone resorption with RANKL binding peptides |
EP3335747B1 (en) | 2011-10-14 | 2021-04-07 | Amgen Inc. | Injector and method of assembly |
MX354988B (es) | 2011-10-25 | 2018-03-28 | Prothena Biosciences Ltd | Formulaciones de anticuerpo y metodos. |
JP6284181B2 (ja) * | 2012-02-09 | 2018-02-28 | 国立研究開発法人理化学研究所 | 環状rna及びタンパク質の製造方法 |
NZ631509A (en) | 2012-03-30 | 2016-09-30 | Daiichi Sankyo Co Ltd | Cdr-modified anti-siglec-15 antibody |
EP2650682A1 (en) | 2012-04-09 | 2013-10-16 | Fundació Privada Institut de Recerca Biomèdica | Method for the prognosis and treatment of cancer metastasis |
US9181572B2 (en) | 2012-04-20 | 2015-11-10 | Abbvie, Inc. | Methods to modulate lysine variant distribution |
US9067990B2 (en) | 2013-03-14 | 2015-06-30 | Abbvie, Inc. | Protein purification using displacement chromatography |
US9150645B2 (en) * | 2012-04-20 | 2015-10-06 | Abbvie, Inc. | Cell culture methods to reduce acidic species |
WO2013176754A1 (en) | 2012-05-24 | 2013-11-28 | Abbvie Inc. | Novel purification of antibodies using hydrophobic interaction chromatography |
EP2856159A4 (en) * | 2012-06-01 | 2016-04-13 | Momenta Pharmaceuticals Inc | METHODS RELATING TO DENOSUMAB |
CA2875918A1 (en) | 2012-06-06 | 2013-12-12 | Fundacio Institut De Recerca Biomedica (Irb Barcelona) | Method for the diagnosis, prognosis and treatment of lung cancer metastasis |
CA2928851A1 (en) | 2012-07-19 | 2014-01-23 | Alethia Biotherapeutics Inc. | Anti-siglec-15 antibodies |
KR20150043523A (ko) | 2012-09-02 | 2015-04-22 | 애브비 인코포레이티드 | 단백질 불균일성의 제어 방법 |
US9512214B2 (en) | 2012-09-02 | 2016-12-06 | Abbvie, Inc. | Methods to control protein heterogeneity |
KR102238677B1 (ko) | 2012-09-07 | 2021-04-12 | 코히러스 바이오사이언시즈, 인코포레이티드 | 아달리무맙의 안정한 수성 제형 |
KR101872965B1 (ko) | 2012-10-12 | 2018-06-29 | 인바이오모션 에스.엘. | C―maf를 이용하는 전립선암 전이의 진단, 예후 및 치료 방법 |
US10119171B2 (en) | 2012-10-12 | 2018-11-06 | Inbiomotion S.L. | Method for the diagnosis, prognosis and treatment of prostate cancer metastasis |
ES2780395T3 (es) | 2012-11-21 | 2020-08-25 | Amgen Inc | Dispositivo de administración de fármacos |
WO2014115022A1 (en) | 2013-01-25 | 2014-07-31 | Baylor College Of Medicine | A helper-dependent adenoviral gene therapy delivery and expression system |
EP2830651A4 (en) | 2013-03-12 | 2015-09-02 | Abbvie Inc | HUMAN ANTIBODIES THAT BIND TNF-ALPHA AND PREPARATION METHODS |
WO2014151878A2 (en) | 2013-03-14 | 2014-09-25 | Abbvie Inc. | Methods for modulating protein glycosylation profiles of recombinant protein therapeutics using monosaccharides and oligosacharides |
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 |
WO2014184679A2 (en) | 2013-03-15 | 2014-11-20 | Inbiomotion S.L. | Method for the prognosis and treatment of renal cell carcinoma metastasis |
JP6577873B2 (ja) | 2013-03-15 | 2019-09-18 | フンダシオ、インスティトゥト、デ、レセルカ、ビオメディカ(イエレベ、バルセロナ)Fundacio Institut De Recerca Biomedica (Irb Barcelona) | がんの転移の予後診断および処置のための方法 |
WO2014149067A1 (en) | 2013-03-15 | 2014-09-25 | Momenta Pharmaceuticals, Inc. | Methods related to ctla4-fc fusion proteins |
JP6336564B2 (ja) | 2013-03-15 | 2018-06-06 | アムゲン・インコーポレーテッド | 薬物カセット、自動注入器、および自動注入器システム |
US10492990B2 (en) | 2013-03-15 | 2019-12-03 | Amgen Inc. | Drug cassette, autoinjector, and autoinjector system |
CN113559363B (zh) | 2013-03-22 | 2023-10-31 | 美国安进公司 | 注射器及装配方法 |
WO2014186310A1 (en) | 2013-05-13 | 2014-11-20 | Momenta Pharmaceuticals, Inc. | Methods for the treatment of neurodegeneration |
US9481901B2 (en) | 2013-05-30 | 2016-11-01 | Amgen Inc. | Methods for increasing mannose content of recombinant proteins |
US10383901B2 (en) | 2013-06-05 | 2019-08-20 | Rebiotix, Inc. | Microbiota restoration therapy (MRT), compositions and methods of manufacture |
US9511099B2 (en) | 2013-06-05 | 2016-12-06 | Rebiotix, Inc. | Microbiota restoration therapy (MRT), compositions and methods of manufacture |
US9782445B2 (en) | 2013-06-05 | 2017-10-10 | Rebiotix, Inc. | Microbiota restoration therapy (MRT), compositions and methods of manufacture |
PL3003330T4 (pl) | 2013-06-05 | 2019-03-29 | Rebiotix, Inc. | Terapia przywracająca mikrobiota (MRT), kompozycje i sposoby wytwarzania |
US9694039B2 (en) | 2013-06-05 | 2017-07-04 | Rebiotix, Inc. | Microbiota restoration therapy (MRT), compositions and methods of manufacture |
US9511100B2 (en) | 2013-06-05 | 2016-12-06 | Rebiotix, Inc. | Microbiota restoration therapy (MRT), compositions and methods of manufacture |
CA2920376A1 (en) | 2013-08-07 | 2015-02-12 | Martin Blomberg JENSEN | Methods and composition comprising denosumab or an antibody or antigen binding domain, fragment or derivative thereof, immunoreactive with a rankl/opgbp peptide for use in the treatment, prevention or alleviation of male infertility |
TW201605896A (zh) | 2013-08-30 | 2016-02-16 | 安美基股份有限公司 | Gitr抗原結合蛋白 |
WO2015047994A2 (en) * | 2013-09-24 | 2015-04-02 | The Board Of Regentsl Of The University Of Texas System | A novel hormone that promotes bone resorption and uses thereof |
US9598667B2 (en) | 2013-10-04 | 2017-03-21 | Abbvie Inc. | Use of metal ions for modulation of protein glycosylation profiles of recombinant proteins |
CN105980576B (zh) | 2013-10-09 | 2021-07-16 | 生物医学研究机构基金会 | 用于源自乳腺癌的骨转移癌的预后和治疗的方法 |
US20160257754A1 (en) | 2013-10-16 | 2016-09-08 | Momenta Pharmaceuticals Inc. | Sialylated glycoproteins |
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 |
US11097055B2 (en) | 2013-10-24 | 2021-08-24 | Amgen Inc. | Injector and method of assembly |
JP7051293B2 (ja) | 2013-10-24 | 2022-04-11 | アムジエン・インコーポレーテツド | 温度感知制御を伴う薬剤送達システム |
WO2015073884A2 (en) | 2013-11-15 | 2015-05-21 | Abbvie, Inc. | Glycoengineered binding protein compositions |
WO2015087187A1 (en) | 2013-12-10 | 2015-06-18 | Rinat Neuroscience Corp. | Anti-sclerostin antibodies |
WO2015094330A1 (en) * | 2013-12-20 | 2015-06-25 | Development Center For Biotechnology | Alpha-enolase specific antibodies and methods of uses in cancer therapy |
CN103965357B (zh) * | 2013-12-31 | 2016-08-17 | 嘉和生物药业有限公司 | 一种抗人rankl抗体 |
WO2015119906A1 (en) | 2014-02-05 | 2015-08-13 | Amgen Inc. | Drug delivery system with electromagnetic field generator |
CN106103465B (zh) | 2014-03-10 | 2021-01-08 | 吉瑞工厂 | 使用预清洗步骤的免疫球蛋白纯化 |
SG11201609219QA (en) | 2014-05-07 | 2016-12-29 | Amgen Inc | Autoinjector with shock reducing elements |
KR102506249B1 (ko) | 2014-06-03 | 2023-03-03 | 암겐 인코포레이티드 | 약물 전달 시스템 및 사용 방법 |
KR102391259B1 (ko) * | 2014-06-04 | 2022-04-26 | 암젠 인크 | 포유류 세포 배양물을 회수하는 방법 |
CA2957960C (en) | 2014-10-14 | 2023-08-22 | Amgen, Inc. | Drug injection device with visual and audible indicators |
CA2967224C (en) | 2014-12-11 | 2023-08-22 | Inbiomotion S.L. | Binding members for human c-maf |
JP6716566B2 (ja) | 2014-12-19 | 2020-07-01 | アムジエン・インコーポレーテツド | 近接センサ付き薬物送達装置 |
EP3233159B1 (en) | 2014-12-19 | 2020-03-04 | Amgen Inc. | Drug delivery device with live button or user interface field |
ES2748750T3 (es) | 2015-02-17 | 2020-03-17 | Amgen Inc | Dispositivo de administración de fármacos con sujeción asistida por vacío y/o realimentación |
US10328123B2 (en) | 2015-02-25 | 2019-06-25 | Saint Louis University | Pulsed introduction of low-dose RANKL as a therapy for atherosclerosis |
US10745461B2 (en) | 2015-02-25 | 2020-08-18 | Saint Louis University | Pulsed introduction of low-dose RANKL as a therapy for diet-induced atherosclerosis |
US10111928B1 (en) * | 2015-02-25 | 2018-10-30 | Saint Louis University | Pulsed introduction of low-dose RANKL as a therapy for osteogenesis imperfecta |
ES2905870T3 (es) | 2015-02-27 | 2022-04-12 | Amgen Inc | Dispositivo de suministro de fármacos que tiene un mecanismo de protección de aguja con un umbral de resistencia ajustable al movimiento de la protección de aguja |
EP4039253A1 (en) | 2015-04-29 | 2022-08-10 | Radius Pharmaceuticals, Inc. | Methods of treating cancer |
US10905726B2 (en) | 2015-06-09 | 2021-02-02 | Rebiotix, Inc. | Microbiota restoration therapy (MRT) compositions and methods of manufacture |
US10799539B2 (en) | 2015-06-09 | 2020-10-13 | Rebiotix, Inc. | Microbiota restoration therapy (MRT) compositions and methods of manufacture |
US10828340B2 (en) | 2015-06-09 | 2020-11-10 | Rebiotix, Inc. | Microbiota restoration therapy (MRT) compositions and methods of manufacture |
ES2889902T3 (es) | 2015-06-09 | 2022-01-14 | Rebiotix Inc | Métodos de fabricación de composiciones para terapia de restauración de la microbiota (TRM) |
HU231463B1 (hu) | 2015-08-04 | 2024-01-28 | Richter Gedeon Nyrt. | Módszer rekombináns proteinek galaktóz tartalmának növelésére |
SG10202101105XA (en) | 2015-08-13 | 2021-03-30 | Amgen Inc | Charged depth filtration of antigen-binding proteins |
WO2017039786A1 (en) | 2015-09-02 | 2017-03-09 | Amgen Inc. | Syringe assembly adapter for a syringe |
US11229702B1 (en) | 2015-10-28 | 2022-01-25 | Coherus Biosciences, Inc. | High concentration formulations of adalimumab |
US11351308B2 (en) | 2015-12-09 | 2022-06-07 | Amgen Inc. | Auto-injector with signaling cap |
US11154661B2 (en) | 2016-01-06 | 2021-10-26 | Amgen Inc. | Auto-injector with signaling electronics |
MA43814A (fr) | 2016-03-08 | 2018-11-28 | Janssen Biotech Inc | Anticorps anti-gitr, méthodes et utilisations |
EP3721922B1 (en) | 2016-03-15 | 2022-05-04 | Amgen Inc. | Reducing probability of glass breakage in drug delivery devices |
WO2017184880A1 (en) | 2016-04-20 | 2017-10-26 | Coherus Biosciences, Inc. | A method of filling a container with no headspace |
WO2017189089A1 (en) | 2016-04-29 | 2017-11-02 | Amgen Inc. | Drug delivery device with messaging label |
WO2017192287A1 (en) | 2016-05-02 | 2017-11-09 | Amgen Inc. | Syringe adapter and guide for filling an on-body injector |
AU2017263558B2 (en) | 2016-05-13 | 2022-12-22 | Amgen Inc. | Vial sleeve assembly |
US11238150B2 (en) | 2016-05-16 | 2022-02-01 | Amgen Inc. | Data encryption in medical devices with limited computational capability |
AU2017271385B2 (en) | 2016-05-25 | 2023-10-05 | Inbiomotion S.L. | Therapeutic treatment of breast cancer based on c-MAF status |
US11541176B2 (en) | 2016-06-03 | 2023-01-03 | Amgen Inc. | Impact testing apparatuses and methods for drug delivery devices |
WO2018004842A1 (en) | 2016-07-01 | 2018-01-04 | Amgen Inc. | Drug delivery device having minimized risk of component fracture upon impact events |
US20190328965A1 (en) | 2016-08-17 | 2019-10-31 | Amgen Inc. | Drug delivery device with placement detection |
MX2019004580A (es) | 2016-10-21 | 2019-08-12 | Amgen Inc | Formulaciones farmaceuticas y metodos para prepararlas. |
US20200261643A1 (en) | 2016-10-25 | 2020-08-20 | Amgen Inc. | On-body injector |
EP3565542B1 (en) | 2017-01-05 | 2024-04-10 | Radius Pharmaceuticals, Inc. | Polymorphic forms of rad1901-2hcl |
AU2018210301A1 (en) | 2017-01-17 | 2019-08-01 | Amgen Inc. | Injection devices and related methods of use and assembly |
JP7064501B2 (ja) | 2017-02-17 | 2022-05-10 | アムジエン・インコーポレーテツド | 無菌流体流路を備える薬物送達デバイスおよび関連する組立方法 |
AU2018221351B2 (en) | 2017-02-17 | 2023-02-23 | Amgen Inc. | Insertion mechanism for drug delivery device |
CA3050927A1 (en) | 2017-03-06 | 2018-09-13 | Brian Stonecipher | Drug delivery device with activation prevention feature |
IL268478B2 (en) | 2017-03-07 | 2023-10-01 | Amgen Inc | Inserting a needle using super pressure |
JP2020509837A (ja) | 2017-03-09 | 2020-04-02 | アムジエン・インコーポレーテツド | 薬剤送達装置のための挿入機構 |
CN110446512B (zh) | 2017-03-28 | 2022-03-18 | 美国安进公司 | 柱塞杆和注射器组件系统以及方法 |
JOP20190255A1 (ar) | 2017-04-28 | 2019-10-27 | Amgen Inc | صيغ أجسام مضادة لـ rankl بشري، وطرق لاستخدامها |
CA3060581A1 (en) | 2017-05-02 | 2018-11-08 | Merck Sharp & Dohme Corp. | Formulations of anti-lag3 antibodies and co-formulations of anti-lag3 antibodies and anti-pd-1 antibodies |
JOP20190260A1 (ar) | 2017-05-02 | 2019-10-31 | Merck Sharp & Dohme | صيغ ثابتة لأجسام مضادة لمستقبل الموت المبرمج 1 (pd-1) وطرق استخدامها |
EP3634546A1 (en) | 2017-06-08 | 2020-04-15 | Amgen Inc. | Torque driven drug delivery device |
US11590294B2 (en) | 2017-06-08 | 2023-02-28 | Amgen Inc. | Syringe assembly for a drug delivery device and method of assembly |
MX2019015472A (es) | 2017-06-22 | 2020-02-19 | Amgen Inc | Reduccion del impacto/choque de la activacion del mecanismo. |
WO2018237225A1 (en) | 2017-06-23 | 2018-12-27 | Amgen Inc. | ELECTRONIC DRUG DELIVERY DEVICE COMPRISING A CAP ACTIVATED BY A SWITCH ASSEMBLY |
EP3651832B1 (en) | 2017-07-14 | 2023-12-13 | Amgen Inc. | Needle insertion-retraction system having dual torsion spring system |
MA49626A (fr) | 2017-07-21 | 2020-05-27 | Amgen Inc | Élément d'étanchéité perméable aux gaz pour récipient à médicament et procédés d'assemblage |
WO2019022950A1 (en) | 2017-07-25 | 2019-01-31 | Amgen Inc. | DRUG DELIVERY DEVICE WITH CONTAINER ACCESS SYSTEM AND ASSEMBLY METHOD THEREOF |
WO2019022951A1 (en) | 2017-07-25 | 2019-01-31 | Amgen Inc. | DRUG DELIVERY DEVICE WITH GEAR MODULE AND ASSEMBLY METHOD THEREOF |
EP3664863A2 (en) | 2017-08-09 | 2020-06-17 | Amgen Inc. | Hydraulic-pneumatic pressurized chamber drug delivery system |
MA49897A (fr) | 2017-08-18 | 2020-06-24 | Amgen Inc | Injecteur sur-corps avec patch adhésif stérile |
US11103636B2 (en) | 2017-08-22 | 2021-08-31 | Amgen Inc. | Needle insertion mechanism for drug delivery device |
WO2019070472A1 (en) | 2017-10-04 | 2019-04-11 | Amgen Inc. | FLOW ADAPTER FOR MEDICATION DELIVERY DEVICE |
CN111132711B (zh) | 2017-10-06 | 2022-07-01 | 安进公司 | 带有联锁组件的药物递送装置及相关组装方法 |
EP3694578A1 (en) | 2017-10-09 | 2020-08-19 | Amgen Inc. | Drug delivery device with drive assembly and related method of assembly |
WO2019090079A1 (en) | 2017-11-03 | 2019-05-09 | Amgen Inc. | System and approaches for sterilizing a drug delivery device |
WO2019090303A1 (en) | 2017-11-06 | 2019-05-09 | Amgen Inc. | Fill-finish assemblies and related methods |
WO2019089178A1 (en) | 2017-11-06 | 2019-05-09 | Amgen Inc. | Drug delivery device with placement and flow sensing |
CA3079665A1 (en) | 2017-11-10 | 2019-05-16 | Amgen Inc. | Plungers for drug delivery devices |
MX2020005066A (es) | 2017-11-16 | 2020-08-20 | Amgen Inc | Autoinyector con deteccion de detencion y punto final. |
WO2019099324A1 (en) | 2017-11-16 | 2019-05-23 | Amgen Inc. | Door latch mechanism for drug delivery device |
US11654153B2 (en) | 2017-11-22 | 2023-05-23 | Inbiomotion S.L. | Therapeutic treatment of breast cancer based on c-MAF status |
US10835685B2 (en) | 2018-05-30 | 2020-11-17 | Amgen Inc. | Thermal spring release mechanism for a drug delivery device |
US11083840B2 (en) | 2018-06-01 | 2021-08-10 | Amgen Inc. | Modular fluid path assemblies for drug delivery devices |
JP7473486B2 (ja) | 2018-07-04 | 2024-04-23 | ラジウス ファーマシューティカルズ,インコーポレイテッド | Rad1901-2hclの多形形態 |
WO2020023220A1 (en) | 2018-07-24 | 2020-01-30 | Amgen Inc. | Hybrid drug delivery devices with tacky skin attachment portion and related method of preparation |
CA3103682A1 (en) | 2018-07-24 | 2020-01-30 | Amgen Inc. | Delivery devices for administering drugs |
US20210228815A1 (en) | 2018-07-24 | 2021-07-29 | Amgen Inc. | Hybrid drug delivery devices with grip portion |
EP3826701A1 (en) | 2018-07-24 | 2021-06-02 | Amgen Inc. | Delivery devices for administering drugs |
EP3829692A1 (en) | 2018-07-31 | 2021-06-09 | Amgen Inc. | Fluid path assembly for a drug delivery device |
MA53724A (fr) | 2018-09-24 | 2021-12-29 | Amgen Inc | Systèmes et procédés de dosage interventionnel |
AU2019350660A1 (en) | 2018-09-28 | 2021-03-18 | Amgen Inc. | Muscle wire escapement activation assembly for a drug delivery device |
AR116679A1 (es) | 2018-10-02 | 2021-06-02 | Amgen Inc | Sistemas de inyección para la administración de fármacos con transmisión de fuerza interna |
EP3860686A1 (en) | 2018-10-05 | 2021-08-11 | Amgen Inc. | Drug delivery device having dose indicator |
SG11202103800RA (en) | 2018-10-15 | 2021-05-28 | Amgen Inc | Drug delivery device having damping mechanism |
CA3109988A1 (en) | 2018-10-15 | 2020-04-23 | Amgen Inc. | Platform assembly process for drug delivery device |
EP3873566A1 (en) | 2018-11-01 | 2021-09-08 | Amgen Inc. | Drug delivery devices with partial drug delivery member retraction |
WO2020092056A1 (en) | 2018-11-01 | 2020-05-07 | Amgen Inc. | Drug delivery devices with partial needle retraction |
MA54057A (fr) | 2018-11-01 | 2022-02-09 | Amgen Inc | Dispositifs d'administration de médicament à rétraction partielle d'élément d'administration de médicament |
HUP1800376A2 (hu) | 2018-11-07 | 2020-05-28 | Richter Gedeon Nyrt | Sejttenyészetben elõállított rekombináns glikoprotein glikozilációs-mintázatának megváltoztatására szolgáló módszer |
HUP1900112A1 (hu) | 2019-04-04 | 2020-10-28 | Richter Gedeon Nyrt | Immunglobulinok affinitás kromatográfiájának fejlesztése kötést megelõzõ flokkulálás alkalmazásával |
US20220160972A1 (en) | 2019-04-24 | 2022-05-26 | Amgen Inc. | Syringe sterilization verification assemblies and methods |
CA3132656A1 (en) | 2019-04-30 | 2020-11-05 | Instituto De Medicina Molecular Joao Lobo Antunes | Rank pathway inhibitors in combination with cdk inhibitors |
CA3148261A1 (en) | 2019-08-23 | 2021-03-04 | Amgen Inc. | Drug delivery device with configurable needle shield engagement components and related methods |
EP4110371A1 (en) | 2020-01-24 | 2023-01-04 | Radius Health, Inc. | Methods of stimulating bone growth with abalopartide and denosumab |
CN113621060B (zh) * | 2020-05-07 | 2023-07-04 | 浙江瑞硕生物技术有限公司 | 一种opg抗体对及其应用 |
WO2022246055A1 (en) | 2021-05-21 | 2022-11-24 | Amgen Inc. | Method of optimizing a filling recipe for a drug container |
WO2024064878A1 (en) | 2022-09-23 | 2024-03-28 | The University Of North Carolina At Chapel Hill | Methods and compositions for the treatment of melanoma |
Family Cites Families (290)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US3773919A (en) | 1969-10-23 | 1973-11-20 | Du Pont | Polylactide-drug mixtures |
US4179337A (en) | 1973-07-20 | 1979-12-18 | Davis Frank F | Non-immunogenic polypeptides |
US4263428A (en) | 1978-03-24 | 1981-04-21 | The Regents Of The University Of California | Bis-anthracycline nucleic acid function inhibitors and improved method for administering the same |
US4399216A (en) | 1980-02-25 | 1983-08-16 | The Trustees Of Columbia University | Processes for inserting DNA into eucaryotic cells and for producing proteinaceous materials |
US4338397A (en) * | 1980-04-11 | 1982-07-06 | President And Fellows Of Harvard College | Mature protein synthesis |
IE52535B1 (en) | 1981-02-16 | 1987-12-09 | Ici Plc | Continuous release pharmaceutical compositions |
US4474893A (en) | 1981-07-01 | 1984-10-02 | The University of Texas System Cancer Center | Recombinant monoclonal antibodies |
EP0088046B1 (de) | 1982-02-17 | 1987-12-09 | Ciba-Geigy Ag | Lipide in wässriger Phase |
US4816567A (en) | 1983-04-08 | 1989-03-28 | Genentech, Inc. | Recombinant immunoglobin preparations |
US4755465A (en) * | 1983-04-25 | 1988-07-05 | Genentech, Inc. | Secretion of correctly processed human growth hormone in E. coli and Pseudomonas |
US4710457A (en) | 1983-06-29 | 1987-12-01 | Sloan-Kettering Institute For Cancer Research | Monoclonal antibody for human hematopoietic glycoproteins and method |
HUT35524A (en) | 1983-08-02 | 1985-07-29 | Hoechst Ag | Process for preparing pharmaceutical compositions containing regulatory /regulative/ peptides providing for the retarded release of the active substance |
DE3474511D1 (en) | 1983-11-01 | 1988-11-17 | Terumo Corp | Pharmaceutical composition containing urokinase |
US4740461A (en) | 1983-12-27 | 1988-04-26 | Genetics Institute, Inc. | Vectors and methods for transformation of eucaryotic cells |
US4699880A (en) | 1984-09-25 | 1987-10-13 | Immunomedics, Inc. | Method of producing monoclonal anti-idiotype antibody |
US5900400A (en) | 1984-12-06 | 1999-05-04 | Amgen Inc. | Serine protease inhibitor analogs |
US4760130A (en) | 1984-12-06 | 1988-07-26 | Synergen Biologicals, Inc. | Serine protease inhibitors and methods for isolation of same |
JPS6291197A (ja) | 1985-10-17 | 1987-04-25 | Dainippon Pharmaceut Co Ltd | 抗ヒトインタ−ロイキン1抗体,その製法及びその使用法 |
US4959455A (en) | 1986-07-14 | 1990-09-25 | Genetics Institute, Inc. | Primate hematopoietic growth factors IL-3 and pharmaceutical compositions |
US4935343A (en) | 1986-08-08 | 1990-06-19 | Syntex (U.S.A.) Inc. | Monoclonal antibodies for interleukin-1β |
US4946778A (en) | 1987-09-21 | 1990-08-07 | Genex Corporation | Single polypeptide chain binding molecules |
EP0281604B1 (en) | 1986-09-02 | 1993-03-31 | Enzon Labs Inc. | Single polypeptide chain binding molecules |
US5260203A (en) | 1986-09-02 | 1993-11-09 | Enzon, Inc. | Single polypeptide chain binding molecules |
DK590387A (da) | 1986-11-13 | 1988-05-14 | Otsuka Pharma Co Ltd | Antistoffer mod interleukin-1 |
US4912040A (en) | 1986-11-14 | 1990-03-27 | Genetics Institute, Inc. | Eucaryotic expression system |
US5359032A (en) | 1987-08-26 | 1994-10-25 | Biogen Inc. | Interkeukin-1 inhibitor |
IL83878A (en) | 1987-09-13 | 1995-07-31 | Yeda Res & Dev | Soluble protein corresponding to tnf inhibitory protein its preparation and pharmaceutical compositions containing it |
IL98078A0 (en) | 1991-05-07 | 1992-06-21 | Yeda Res & Dev | Pharmaceutical compositions comprising an anticytokyne |
US5512544A (en) | 1987-09-13 | 1996-04-30 | Yeda Research And Development Co. Ltd. | Pharmaceutical compositions comprising an anticytokine |
US4892538A (en) | 1987-11-17 | 1990-01-09 | Brown University Research Foundation | In vivo delivery of neurotransmitters by implanted, encapsulated cells |
US5106627A (en) | 1987-11-17 | 1992-04-21 | Brown University Research Foundation | Neurological therapy devices |
US5319071A (en) | 1987-11-25 | 1994-06-07 | Immunex Corporation | Soluble interleukin-1 receptors |
US4968607A (en) | 1987-11-25 | 1990-11-06 | Immunex Corporation | Interleukin-1 receptors |
WO1989004838A1 (en) | 1987-11-25 | 1989-06-01 | Immunex Corporation | Interleukin-1 receptors |
US5846534A (en) | 1988-02-12 | 1998-12-08 | British Technology Group Limited | Antibodies to the antigen campath-1 |
US4942184A (en) * | 1988-03-07 | 1990-07-17 | The United States Of America As Represented By The Department Of Health And Human Services | Water soluble, antineoplastic derivatives of taxol |
GB8807803D0 (en) | 1988-03-31 | 1988-05-05 | Glaxo Group Ltd | Biochemical product |
US5075222A (en) | 1988-05-27 | 1991-12-24 | Synergen, Inc. | Interleukin-1 inhibitors |
US5011472A (en) | 1988-09-06 | 1991-04-30 | Brown University Research Foundation | Implantable delivery system for biological factors |
US5811261A (en) | 1988-09-12 | 1998-09-22 | Yeda Research And Development Co. Ltd. | Expression of the recombinant tumor necrosis factor binding protein I (TBP-I) |
US5359037A (en) | 1988-09-12 | 1994-10-25 | Yeda Research And Development Co. Ltd. | Antibodies to TNF binding protein I |
IL94039A (en) | 1989-08-06 | 2006-09-05 | Yeda Res & Dev | Antibodies to tbp - 1 and their use |
DE68925935T2 (de) | 1988-10-01 | 1996-08-14 | Otsuka Pharma Co Ltd | Antikörper gegen Interleukin-1-beta |
FR2640146B1 (fr) | 1988-12-08 | 1993-12-24 | Commissariat A Energie Atomique | Anticorps monoclonaux anti-interleukines 1(alpha) et 1(beta), leur procede de production et applications desdits anticorps a la detection des interleukines 1(alpha) et 1(beta) et en therapeutique |
US5530101A (en) | 1988-12-28 | 1996-06-25 | Protein Design Labs, Inc. | Humanized immunoglobulins |
ATE289350T1 (de) | 1989-04-21 | 2005-03-15 | Amgen Inc | Tnf-rezeptor, tnf bindende proteine und dafür kodierende dnas |
DE3922089A1 (de) | 1989-05-09 | 1990-12-13 | Basf Ag | Neue proteine und ihre herstellung |
IL107267A (en) | 1993-10-12 | 2009-07-20 | Yeda Res & Dev | Ligand to a member of the tnf/ngf receptor family |
AU636608B2 (en) | 1989-05-18 | 1993-05-06 | Yeda Research And Development Co. Ltd. | Tumor necrosis factor binding protein II, it's purification and antibodies thereto |
AU648505B2 (en) | 1989-05-19 | 1994-04-28 | Amgen, Inc. | Metalloproteinase inhibitor |
US5627262A (en) | 1989-07-05 | 1997-05-06 | The Board Of Regents Of The University Of Oklahoma | Method and composition for the treatment of septic shock |
IL95031A (en) | 1989-07-18 | 2007-03-08 | Amgen Inc | A method of producing a recombinant human necrotic factor absorber |
WO1991003553A1 (en) | 1989-09-05 | 1991-03-21 | Immunex Corporation | TUMOR NECROSIS FACTOR-α AND -β RECEPTORS |
US5395760A (en) | 1989-09-05 | 1995-03-07 | Immunex Corporation | DNA encoding tumor necrosis factor-α and -β receptors |
ATE194384T1 (de) | 1989-09-12 | 2000-07-15 | Hoffmann La Roche | Tnf-bindende proteine |
JPH03127800A (ja) | 1989-10-13 | 1991-05-30 | Teijin Ltd | 腫瘍壊死因子活性抑制物質 |
CA2068320C (en) | 1989-11-29 | 2000-10-17 | Robert Hageman | Production of recombinant human interleukin-1 inhibitor |
EP0433900B1 (en) | 1989-12-13 | 1995-09-20 | Yeda Research And Development Company Limited | Expression of the recombinant tumor necrosis factor binding protein I (TBP-I) |
US5136021A (en) | 1990-02-27 | 1992-08-04 | Health Research, Inc. | TNF-inhibitory protein and a method of production |
AU649245B2 (en) | 1990-04-02 | 1994-05-19 | Amgen, Inc. | Methods for treating interleukin-1 mediated diseases |
US6552170B1 (en) | 1990-04-06 | 2003-04-22 | Amgen Inc. | PEGylation reagents and compounds formed therewith |
US5151510A (en) | 1990-04-20 | 1992-09-29 | Applied Biosystems, Inc. | Method of synethesizing sulfurized oligonucleotide analogs |
WO1991017184A1 (en) | 1990-04-27 | 1991-11-14 | The Upjohn Company | Modified interleukin-1 inhibitors |
US5872095A (en) | 1990-05-01 | 1999-02-16 | Chiron Corporation | IL-1 receptor antagonists medicaments |
ATE178094T1 (de) | 1990-05-01 | 1999-04-15 | Chiron Corp | Interleukin-i antagonist und seine verwendung |
US5350683A (en) | 1990-06-05 | 1994-09-27 | Immunex Corporation | DNA encoding type II interleukin-1 receptors |
GB2246569A (en) | 1990-06-15 | 1992-02-05 | Charing Cross Sunley Research | Tumour necrosis factor - alpha binding protein |
ATE309376T1 (de) | 1990-06-28 | 2005-11-15 | Hoechst Ag | Fusionsproteine mit immunglobulinanteilen, ihre herstellung und verwendung |
WO1992001002A1 (fr) | 1990-07-11 | 1992-01-23 | Teijin Limited | Inhibiteur de l'activite du facteur de la necrose tumorale et son procede de preparation |
US5420154A (en) | 1990-08-03 | 1995-05-30 | Smithkline Beecham Corp. | TNF inhibitors |
WO1993012227A1 (en) | 1991-12-17 | 1993-06-24 | Genpharm International, Inc. | Transgenic non-human animals capable of producing heterologous antibodies |
US5824549A (en) | 1990-10-09 | 1998-10-20 | Chiron Corporation | Transformed human T cell |
GB9022648D0 (en) | 1990-10-18 | 1990-11-28 | Charing Cross Sunley Research | Polypeptide and its use |
US5858355A (en) | 1990-12-20 | 1999-01-12 | University Of Pittsburgh Of The Commonwealth System Of Higher Education | IRAP gene as treatment for arthritis |
NZ241311A (en) | 1991-01-17 | 1995-03-28 | Gen Hospital Corp | Rna sequence having trans-splicing activity, plant strains |
SG63617A1 (en) | 1991-01-18 | 1999-03-30 | Amgen Boulder Inc | Methods for treating tumar necrosis factor mediated diseases |
SG47099A1 (en) | 1991-03-15 | 1998-03-20 | Amgen Boulder Inc | Pegylation of polypeptides |
IL99120A0 (en) | 1991-08-07 | 1992-07-15 | Yeda Res & Dev | Multimers of the soluble forms of tnf receptors,their preparation and pharmaceutical compositions containing them |
DE69230862T2 (de) | 1991-10-15 | 2000-12-14 | Michael F Mullarkey | Rezeptoren zur Behandlung von Entzündungen vom verzögerten Typ |
US5961974A (en) | 1991-10-25 | 1999-10-05 | Immunex Corporation | Monoclonal antibodies to CD40 ligand, pharmaceutical composition comprising the same and hybridomas producing the same |
ES2038546B1 (es) | 1991-11-08 | 1994-02-16 | Andromaco Lab | Procedimiento de obtencion de un producto de naturaleza polipeptidica con actividad inhibidora de la hiperproduccion del factor de necrosis tumoral. |
JPH05244982A (ja) * | 1991-12-06 | 1993-09-24 | Sumitomo Chem Co Ltd | 擬人化b−b10 |
MX9300141A (es) | 1992-01-13 | 1994-07-29 | Smithkline Beecham Corp | Compuestos de imidazol novedosos, procedimiento para su preparacion y composiciones farmaceuticas que lo contienen. |
WO1993017684A2 (en) | 1992-03-04 | 1993-09-16 | Cell Therapeutics, Inc. | Enantiomeric hydroxylated xanthine compounds |
AU671116B2 (en) | 1992-03-30 | 1996-08-15 | Immunex Corporation | Fusion proteins comprising tumor necrosis factor receptor |
DK0639079T3 (da) | 1992-04-30 | 2000-06-13 | Amgen Inc | Fremgangsmåder til behandling af interleukin-1- og tumornekrosefaktor-medierede sygdomme |
JPH05312248A (ja) | 1992-05-08 | 1993-11-22 | Nissan Motor Co Ltd | シフトレバー装置 |
DE4219626A1 (de) | 1992-06-16 | 1993-12-23 | Wehling Peter Priv Doz Dr Med | Methode zur Einschleusung therapeutisch relevanter Gene in Körperzellen |
JPH0630788A (ja) | 1992-07-16 | 1994-02-08 | Otsuka Pharmaceut Co Ltd | ヒトインターロイキン−1に対する組換え抗体 |
US5545716A (en) | 1992-09-08 | 1996-08-13 | University Of Florida | Superantigen agonist and antagonist peptides |
CA2141953C (en) | 1992-09-17 | 2008-04-08 | Benjamin K. Sabados | Pharmaceutical formulations of interleukin-1 inhibitors |
JPH06111399A (ja) | 1992-09-30 | 1994-04-22 | Sony Corp | 光磁気記録媒体及びその製造方法 |
US5646154A (en) | 1992-10-07 | 1997-07-08 | Sumitomo Pharmaceuticals Co., Ltd. | Pharmaceutical compositions for inhibiting the formation of tumor necrosis factor |
US5891438A (en) * | 1992-10-30 | 1999-04-06 | The Regents Of The University Of California | Method for stimulating production of variable region gene family restricted antibodies through B-cell superantigen vaccination |
US5866576A (en) | 1992-12-16 | 1999-02-02 | Cell Therapeutics, Inc. | Epoxide-containing compounds |
EP0607776B1 (de) | 1993-01-08 | 1998-12-09 | Hoechst Aktiengesellschaft | Verwendung von Leflunomid zur Hemmung von Tumornekrosefaktor alpha |
DK0614984T4 (da) | 1993-03-05 | 2010-12-20 | Bayer Healthcare Llc | Humane monoklonale anti-TNF-alfa-antistoffer |
WO1994020517A1 (en) | 1993-03-08 | 1994-09-15 | University Of Pittsburgh Of The Commonwealth System Of Higher Education | Gene transfer for treating a connective tissue of a mammalian host |
JP3723206B2 (ja) | 1993-03-19 | 2005-12-07 | バクスイン・エス・アー | ムラミルペプチドとサイトカインとを組み合わせることを特徴とするヒトに用いる治療用組成物 |
US6326353B1 (en) | 1993-03-23 | 2001-12-04 | Sequus Pharmaceuticals, Inc. | Enhanced circulation effector composition and method |
US5843905A (en) | 1993-06-04 | 1998-12-01 | Vertex Pharmaceuticals, Incorporated | Peptidic phosphinyloxymethyl ketones as interleukin-1β-converting enzyme inhibitors |
FR2706772A1 (en) | 1993-06-22 | 1994-12-30 | Vacsyn Sa | Prevention and treatment of septic syndrome with an immunosuppressant, in particular cyclosporin. |
US5698579A (en) | 1993-07-02 | 1997-12-16 | Celgene Corporation | Cyclic amides |
WO1995001997A1 (en) | 1993-07-09 | 1995-01-19 | Smithkline Beecham Corporation | RECOMBINANT AND HUMANIZED IL-1β ANTIBODIES FOR TREATMENT OF IL-1 MEDIATED INFLAMMATORY DISORDERS IN MAN |
EP0711282B1 (en) | 1993-07-28 | 2002-06-05 | Aventis Pharma Limited | Compounds as pde iv and tnf inhibitors |
ATE177083T1 (de) | 1993-11-29 | 1999-03-15 | Merrell Pharma Inc | Benzolsulfonyliminderivate als inhibitoren der il-1 wirkung |
CA2138305A1 (en) | 1993-12-28 | 1995-06-29 | Naohito Ohashi | Tumor necrosis factor production inhibitors |
GB9401460D0 (en) | 1994-01-26 | 1994-03-23 | Rhone Poulenc Rorer Ltd | Compositions of matter |
US5608035A (en) | 1994-02-02 | 1997-03-04 | Affymax Technologies N.V. | Peptides and compounds that bind to the IL-1 receptor |
CA2183562A1 (en) | 1994-02-18 | 1995-08-24 | J. Peter Klein | Intracellular signalling mediators |
ES2118557T3 (es) | 1994-03-09 | 1998-09-16 | Pfizer | Compuestos de isoxazolina como inhibidores de la liberacion de tnf. |
US5708142A (en) | 1994-05-27 | 1998-01-13 | Genentech, Inc. | Tumor necrosis factor receptor-associated factors |
US5817822A (en) | 1994-06-24 | 1998-10-06 | Novartis Corporation | Certain alpha-azacycloalkyl substituted arylsulfonamido acetohydroxamic acids |
IL114417A0 (en) | 1994-07-07 | 1995-10-31 | Res Dev Foundation | Tumor necrosis factor receptor-I associated proteins and protein kinase and methods for their use |
US5877180A (en) | 1994-07-11 | 1999-03-02 | University Of Virginia Patent Foundation | Method for treating inflammatory diseases with A2a adenosine receptor agonists |
DE69519454T2 (de) | 1994-07-14 | 2001-05-03 | Hayashibara Biochem Lab | Protein, das Interferon-Gamma Herstellung induziert und monoklonaler Antikörper dagegen |
US5641747A (en) | 1994-07-25 | 1997-06-24 | Temple University-Of The Commonwealth System Of Higher Education | Treatment of osteopetrotic diseases |
US5633227A (en) | 1994-09-12 | 1997-05-27 | Miles, Inc. | Secretory leukocyte protease inhibitor as an inhibitor of tryptase |
IT1269989B (it) | 1994-09-21 | 1997-04-16 | Dompe Spa | Antagonisti recettoriali di il-1 ad aumentata attivita' inibitoria |
CZ288436B6 (en) | 1994-10-05 | 2001-06-13 | Darwin Discovery Ltd | Peptidyl derivatives, their therapeutic use as inhibitors of metalloproteinases and pharmaceutical preparation in which they are comprised |
US5852173A (en) | 1994-10-19 | 1998-12-22 | Genetics Institute, Inc. | TNF receptor death ligand proteins and inhibitors of ligand binding |
TW464656B (en) | 1994-11-15 | 2001-11-21 | Hayashibara Biochem Lab | Interferon-gamma production inducing polypeptide monoclonal antibody, and agent for interferon-gamma susceptive disease |
JPH10511398A (ja) | 1994-12-23 | 1998-11-04 | スミスクライン・ビーチャム・コーポレイション | 4,4−(二置換)シクロヘキサン−1−カルボキシレート単量体および関連する化合物 |
ZA9510826B (en) | 1994-12-23 | 1996-06-20 | Smithkline Beecham Corp | 3,3-(disubstituted)cyclohexan-1-ol monomers and related compounds |
US6323201B1 (en) | 1994-12-29 | 2001-11-27 | The Regents Of The University Of California | Compounds for inhibition of ceramide-mediated signal transduction |
US6429221B1 (en) | 1994-12-30 | 2002-08-06 | Celgene Corporation | Substituted imides |
AU694295B2 (en) | 1995-01-09 | 1998-07-16 | Otsuka Pharmaceutical Co., Ltd. | Use of carbostyril compounds for inhibition of TNF-alpha |
PE64396A1 (es) | 1995-01-23 | 1997-01-28 | Hoffmann La Roche | Proteina accesoria del receptor de la interleucina 1 |
CZ266797A3 (cs) | 1995-02-23 | 1998-03-18 | Novartis Nutrition Ag | Použití glycinu, jeho prekurzorů a solí k přípravě léčiva nebo nutriční formulace pro snižování hladin TNF a léčivo, které tyto aminokyseliny obsahuje |
WO1996028546A1 (en) | 1995-03-15 | 1996-09-19 | Human Genome Sciences, Inc. | Human tumor necrosis factor receptor |
EP0737471A3 (fr) | 1995-04-10 | 2000-12-06 | L'oreal | Utilisation d'un sel d'une métal alcalino-terreux comme inhibiteur de TNF-alpha dans une composition unique et composition obtenue |
CA2218503C (en) | 1995-04-20 | 2001-07-24 | Pfizer Inc. | Arylsulfonyl hydroxamic acid derivatives |
CA2217850A1 (en) | 1995-05-10 | 1996-11-14 | Chirotech Technology Limited | Peptide compounds which inhibit metalloproteinase and tnf liberation, and their therapeutic use |
AR004471A1 (es) | 1995-05-31 | 1998-12-16 | Smithkline Beecham Corp | Compuestos de ciclohexan-1-ol-4,4-disustituidos, utiles en el tratamiento de enfermedades alergicas e inflamatorias y composiciones farmaceuticas que lascontienen |
US5817476A (en) | 1995-06-07 | 1998-10-06 | Genetics Institute, Inc. | Polynucleotides encoding interleukin-1 receptor intracellular ligand proteins |
US5739143A (en) | 1995-06-07 | 1998-04-14 | Smithkline Beecham Corporation | Imidazole compounds and compositions |
US5843901A (en) | 1995-06-07 | 1998-12-01 | Advanced Research & Technology Institute | LHRH antagonist peptides |
US5830742A (en) | 1995-06-08 | 1998-11-03 | Immunex Corporation | TNF-α converting enzyme |
US5763223A (en) | 1995-06-29 | 1998-06-09 | Immunex Corporation | DNA encoding a cytokine that induces apoptosis |
US6127977A (en) | 1996-11-08 | 2000-10-03 | Cohen; Nathan | Microstrip patch antenna with fractal structure |
ZA966663B (en) | 1995-08-17 | 1998-02-06 | Genentech Inc | Traf Inhibitors. |
US5728844A (en) | 1995-08-29 | 1998-03-17 | Celgene Corporation | Immunotherapeutic agents |
WO1997008174A1 (en) | 1995-08-31 | 1997-03-06 | Smithkline Beecham Corporation | Interleukin converting enzyme and apoptosis |
IL115245A (en) | 1995-09-11 | 2002-12-01 | Yissum Res Dev Co | Tumor necrosis factor inhibiting pharmaceuticals |
US5968755A (en) | 1995-09-27 | 1999-10-19 | The Board Of Trustees Of The Leland Stanford Junior University | Methods for determining T-cell profiles of immunocompromised subjects |
CN1145637C (zh) | 1995-10-05 | 2004-04-14 | 达尔文发现有限公司 | 作为金属蛋白酶和tnf释放抑制剂的硫取代的肽 |
DE19540475A1 (de) | 1995-10-20 | 1997-04-24 | Schering Ag | Chirale Methylphenyloxazolidinone |
CN1202161A (zh) | 1995-11-14 | 1998-12-16 | 杜邦麦克药品公司 | 作为金属蛋白酶抑制剂的新的大环化合物 |
US6281352B1 (en) | 1995-11-14 | 2001-08-28 | Dupont Pharmaceuticals Company | Macrocyclic compounds as metalloprotease inhibitors |
US6090382A (en) | 1996-02-09 | 2000-07-18 | Basf Aktiengesellschaft | Human antibodies that bind human TNFα |
CO4750805A1 (es) * | 1995-12-13 | 1999-03-31 | Sumitomo Chemical Co | Compuesto para champu |
US5869315A (en) | 1995-12-18 | 1999-02-09 | Basf Aktiengesellschaft | Modified interleukin-1β converting enzyme with increased stability |
US5990119A (en) | 1995-12-21 | 1999-11-23 | Smithkline Beecham Corporation | 1,4,4-(trisubstituted)cyclohexane monomers and related compounds |
US5891883A (en) | 1995-12-21 | 1999-04-06 | Smithkline Beecham Corporation | 4,4-(disubstituted)cyclohexan-1-ols monomers and related compounds |
US5869677A (en) | 1995-12-21 | 1999-02-09 | Smithkline Beecham Corporation | 3,3-(disubstituted)cyclohexan-1-carboxylate monomers and related compounds |
US6613544B1 (en) * | 1995-12-22 | 2003-09-02 | Amgen Inc. | Osteoprotegerin |
US6369027B1 (en) | 1995-12-22 | 2002-04-09 | Amgen Inc. | Osteoprotegerin |
CA2238885A1 (en) | 1995-12-29 | 1997-07-10 | Incyte Pharmaceuticals, Inc. | Nucleic acids encoding interferon gamma inducing factor-2 |
US6046048A (en) | 1996-01-09 | 2000-04-04 | Genetech, Inc. | Apo-2 ligand |
KR20040010739A (ko) | 1996-02-09 | 2004-01-31 | 암젠 인코포레이티드 | 인터루킨-1 수용체 길항물질을 포함하는 융합 단백질 및 이를 포함하는 제약학적 조성물 |
RU2270030C2 (ru) | 1996-02-09 | 2006-02-20 | Абботт Байотекнолоджи эЛтиди. | СПОСОБ ИНГИБИРОВАНИЯ АКТИВНОСТИ ЧЕЛОВЕЧЕСКОГО TNFα (ВАРИАНТЫ), ПРИМЕНЕНИЕ ВЫДЕЛЕННОГО АНТИТЕЛА ЧЕЛОВЕКА ИЛИ ЕГО АНТИГЕНСВЯЗЫВАЮЩЕГО ФРАГМЕНТА В КАЧЕСТВЕ КОМПОНЕНТА ДЛЯ ПРОИЗВОДСТВА ЛЕКАРСТВЕННОГО СРЕДСТВА (ВАРИАНТЫ) И ВЫДЕЛЕННОЕ ЧЕЛОВЕЧЕСКОЕ АНТИТЕЛО ИЛИ ЕГО АНТИГЕНСВЯЗЫВАЮЩИЙ ФРАГМЕНТ |
US5994351A (en) | 1998-07-27 | 1999-11-30 | Pfizer Inc. | Arylsulfonylamino hydroxamic acid derivatives |
US5981220A (en) | 1996-03-27 | 1999-11-09 | Human Genome Sciences, Inc. | Epidermal differentiation factor |
GB9607249D0 (en) | 1996-04-04 | 1996-06-12 | Chiroscience Ltd | Compounds |
GB9607120D0 (en) | 1996-04-04 | 1996-06-12 | Chiroscience Ltd | Compounds |
GB9607119D0 (en) | 1996-04-04 | 1996-06-12 | Chiroscience Ltd | Compounds |
US5710013A (en) | 1996-04-19 | 1998-01-20 | Tularik Inc. | Tumor necrosis factor receptor associated factor 6 (TRAF6) |
GB9609795D0 (en) | 1996-05-10 | 1996-07-17 | Smithkline Beecham Plc | Novel compounds |
AUPO048296A0 (en) | 1996-06-14 | 1996-07-11 | Fujisawa Pharmaceutical Co., Ltd. | New compound and its preparation |
EP1669454A3 (en) | 1996-06-27 | 2009-04-01 | Kabushiki Kaisha Hayashibara Seibutsu Kagaku Kenkyujo | Genomic DNA encoding a polypeptide capable of inducing the production of interferon-gamma |
EP0818439B1 (en) | 1996-07-02 | 1999-10-13 | Nisshin Flour Milling Co., Ltd. | Imide derivatives |
TW555765B (en) | 1996-07-09 | 2003-10-01 | Amgen Inc | Low molecular weight soluble tumor necrosis factor type-I and type-II proteins |
JPH10130149A (ja) | 1996-07-12 | 1998-05-19 | Sankyo Co Ltd | Tnf産生抑制剤 |
US5853977A (en) | 1996-07-12 | 1998-12-29 | Schering Corporation | Mammalian TNF-α convertases |
US5877222A (en) | 1996-07-19 | 1999-03-02 | The Regents Of The University Of California | Method for treating aids-associated dementia |
GB9616643D0 (en) | 1996-08-08 | 1996-09-25 | Chiroscience Ltd | Compounds |
NZ334148A (en) | 1996-08-12 | 2001-12-21 | Celgene Corp | 3-Substituted phenyl-ethyl or ethenyl derivatives terminated with a nitrile, alkane, carboxyl or carbamoyl group useful to reduce cytokine levels |
US6069132A (en) | 1996-08-14 | 2000-05-30 | Revanker; Ganapathi R. | Phosphazole compounds |
ES2217428T3 (es) | 1996-09-25 | 2004-11-01 | Ss Pharmaceutical Co., Ltd. | Derivados de vinilpiridina sustituidos y medicamentos que los contienen. |
US5962481A (en) | 1996-10-16 | 1999-10-05 | American Cyanamid Company | Preparation and use of ortho-sulfonamido heteroaryl hydroxamic acids as matrix metalloproteinase and tace inhibitors |
GB9621859D0 (en) | 1996-10-21 | 1996-12-11 | Xenova Ltd | Cytokine production inhibitors |
GB9712761D0 (en) | 1997-06-17 | 1997-08-20 | Chiroscience Ltd | Quinolines and their therapeutic use |
JPH10147531A (ja) | 1996-11-19 | 1998-06-02 | Otsuka Pharmaceut Co Ltd | TNF−α産生抑制剤 |
US5955480A (en) | 1996-11-20 | 1999-09-21 | Merck & Co., Inc. | Triaryl substituted imidazoles, compositions containing such compounds and methods of use |
AU728760B2 (en) | 1996-11-20 | 2001-01-18 | Merck & Co., Inc. | Triaryl substituted imidazoles, compositions containing such compounds and methods of use |
US5834435A (en) | 1996-11-27 | 1998-11-10 | Slesarev; Vladimir I. | Inhibition of TNF-α pleiotropic and cytotoxic effects |
DK1500329T3 (da) | 1996-12-03 | 2012-07-09 | Amgen Fremont Inc | Humane antistoffer, der specifikt binder TNF-alfa |
AU5696198A (en) | 1996-12-06 | 1998-06-29 | Amgen, Inc. | Combination therapy using a tnf binding protein for treating tnf-mediated diseases |
DE19652227A1 (de) | 1996-12-16 | 1998-06-18 | Bosch Gmbh Robert | Verfahren und Vorrichtung zum Zuordnen einer Fernbedienung zu einer Basisstation |
JPH10231285A (ja) | 1996-12-17 | 1998-09-02 | Ishihara Sangyo Kaisha Ltd | フタルイミド誘導体又はその塩、それらの製造方法及びそれらを含有する医薬組成物 |
US6271349B1 (en) | 1996-12-23 | 2001-08-07 | Immunex Corporation | Receptor activator of NF-κB |
EP2003203A1 (en) | 1996-12-23 | 2008-12-17 | Immunex Corporation | Ligand for receptor activator of nf-kappa b, ligand is member of TNF superfamily |
US7141393B2 (en) | 1996-12-26 | 2006-11-28 | Kabushiki Kaisha Hayashibara Seibutsu Kagaku Kenkyujo | Interleukin-18-receptor proteins |
PT853083E (pt) | 1997-01-06 | 2001-12-28 | Pfizer | Composto de piridilfurano e piridiltiofeno e sua utilizacao farmaceutica |
ZA9818B (en) | 1997-01-07 | 1998-07-02 | Abbott Lab | C-terminal ketone inhibitors of matrix metalloproteinases and tnf alpha secretion |
US5952320A (en) | 1997-01-07 | 1999-09-14 | Abbott Laboratories | Macrocyclic inhibitors of matrix metalloproteinases and TNFα secretion |
US6054559A (en) | 1997-01-28 | 2000-04-25 | Smithkline Beecham Corporation | Interleukin-1 receptor antagonist beta (IL-1raβ) |
JP3573757B2 (ja) | 1997-01-29 | 2004-10-06 | ファイザー・インク | スルホニルウレア誘導体、およびインターロイキン−1の活性を制御する上でのスルホニルウレア誘導体の使用 |
JP3955352B2 (ja) * | 1997-02-25 | 2007-08-08 | 株式会社林原生物化学研究所 | 破骨細胞形成阻害剤 |
US5969102A (en) | 1997-03-03 | 1999-10-19 | St. Jude Children's Research Hospital | Lymphocyte surface receptor that binds CAML, nucleic acids encoding the same and methods of use thereof |
US6638952B1 (en) | 1997-03-04 | 2003-10-28 | Pharmacia Corporation | Aromatic sulfonyl alpha-cycloamino hydroxamic acid compounds |
WO1998039316A1 (en) | 1997-03-04 | 1998-09-11 | Monsanto Company | N-hydroxy 4-sulfonyl butanamide compounds |
BR9808214A (pt) | 1997-03-04 | 2000-05-16 | Monsanto Co | Compostos de n-hidróxi 4-sulfonil butanamida |
EP0977745B1 (en) | 1997-03-04 | 2004-12-01 | Pharmacia Corporation | Thioaryl sulfonamide hydroxamic acid compounds |
US6362183B1 (en) | 1997-03-04 | 2002-03-26 | G. D. Searle & Company | Aromatic sulfonyl alpha-hydroxy hydroxamic acid compounds |
US6087116A (en) | 1997-03-12 | 2000-07-11 | Kabushiki Kaisha Hayashibara Seibutsu Kagaku Kenkyujo | Interleukin-18 (IL-18) receptor polypeptides and their uses |
US6054487A (en) | 1997-03-18 | 2000-04-25 | Basf Aktiengesellschaft | Methods and compositions for modulating responsiveness to corticosteroids |
PL336464A1 (en) | 1997-03-18 | 2000-06-19 | Basf Ag | Method of and compositions for modulating reactivity in respect to corticosteroids i |
JPH10259140A (ja) | 1997-03-18 | 1998-09-29 | Sumitomo Pharmaceut Co Ltd | 腫瘍壊死因子産生抑制剤 |
AU6769298A (en) | 1997-03-21 | 1998-10-20 | Cistron Biotechnology, Inc. | Method for inhibiting cleavage of precursor il-1beta |
GB9706255D0 (en) | 1997-03-26 | 1997-05-14 | Smithkline Beecham Plc | Novel compounds |
WO1998043959A1 (en) | 1997-03-28 | 1998-10-08 | Zeneca Limited | Hydroxamic acids substituted by heterocycles useful for inhibition of tumor necrosis factor |
AU6843498A (en) | 1997-03-28 | 1998-10-22 | Zeneca Limited | Process for the preparation of n-(3-hydroxy-succinyl)-amino acid derivatives |
AU738037B2 (en) | 1997-04-04 | 2001-09-06 | Pfizer Products Inc. | Nicotinamide derivatives |
US6117654A (en) | 1997-08-04 | 2000-09-12 | Millennium Biotherapeutics, Inc. | Nucleic acid molecules encoding Tango-77-polypeptides |
DE69830582T2 (de) | 1997-04-10 | 2006-05-04 | Agennix, Inc., Houston | Verwendung von lactoferrin in der behandlung von beschwerden, die von allergenen verursacht sind |
HU229841B1 (en) | 1997-04-15 | 2014-09-29 | Daiichi Sankyo Co Ltd | Antibodies against obm |
WO1998046751A1 (en) | 1997-04-16 | 1998-10-22 | Amgen Inc. | Osteoprotegerin binding proteins and receptors |
US5843678A (en) | 1997-04-16 | 1998-12-01 | Amgen Inc. | Osteoprotegerin binding proteins |
US6316408B1 (en) * | 1997-04-16 | 2001-11-13 | Amgen Inc. | Methods of use for osetoprotegerin binding protein receptors |
FR2762315B1 (fr) | 1997-04-22 | 1999-05-28 | Logeais Labor Jacques | Derives d'amino-acides inhibiteurs des metalloproteases de la matrice extracellulaire et de la liberation du tnf alpha |
EP1028954B1 (en) | 1997-04-24 | 2003-07-02 | Ortho-McNeil Pharmaceutical, Inc. | Substituted imidazoles useful in the treatment of inflammatory diseases |
FR2762514B1 (fr) | 1997-04-29 | 1999-10-22 | Sanofi Sa | Utilisation de derives de la tetrahydropyridine pour la preparation de medicaments pour le traitement des maladies entrainant une demyelinisation |
JP3776203B2 (ja) | 1997-05-13 | 2006-05-17 | 第一製薬株式会社 | Icam−1産生阻害剤 |
EP0983260A2 (en) | 1997-05-22 | 2000-03-08 | G.D. Searle & Co. | 3(5)-HETEROARYL SUBSTITUTED PYRAZOLES AS p38 KINASE INHIBITORS |
US6265535B1 (en) | 1997-05-30 | 2001-07-24 | The Trustees Of The University Of Pennsylvania | Peptides and peptide analogues designed from binding sites of tumor necrosis factor receptor superfamily and their uses |
JPH111481A (ja) | 1997-06-10 | 1999-01-06 | Sumitomo Pharmaceut Co Ltd | ピペリジニルフタラジン誘導体 |
KR19990001101A (ko) | 1997-06-12 | 1999-01-15 | 손경식 | 캐테콜 아미노산 유도체, 이의 제조방법 및 그를 함유한 약제 조성물 |
PL199893B1 (pl) | 1997-06-12 | 2008-11-28 | Rhone Poulenc Rorer Ltd | Imidazolilo-cykliczne acetale, kompozycja farmaceutyczna oraz zastosowanie imidazolilo-cyklicznych acetali |
JP2002504909A (ja) | 1997-06-13 | 2002-02-12 | スミスクライン・ビーチャム・コーポレイション | 新規な置換ピラゾールおよびピラゾリン化合物 |
GB9713732D0 (en) | 1997-06-27 | 1997-09-03 | Pharmacia & Upjohn Spa | Substituted triazinic compounds |
GB9713733D0 (en) | 1997-06-27 | 1997-09-03 | Pharmacia & Upjohn Spa | Poly-branched polycarboxamido compounds |
GB9713726D0 (en) | 1997-06-30 | 1997-09-03 | Ciba Geigy Ag | Organic compounds |
US6235787B1 (en) | 1997-06-30 | 2001-05-22 | Hoffmann-La Roche Inc. | Hydrazine derivatives |
KR20010014288A (ko) | 1997-06-30 | 2001-02-26 | 오르토-맥네일 파마슈티칼, 인코퍼레이티드 | 염증성 질환의 치료에 유용한 2-치환된 이미다졸 |
US5843721A (en) | 1997-07-03 | 1998-12-01 | Tularik Inc. | Nucleic acids encoding human NIK protein |
WO1999001139A1 (en) | 1997-07-03 | 1999-01-14 | Thomas Jefferson University | An improved method for design and selection of efficacious antisense oligonucleotides |
WO1999002510A1 (en) | 1997-07-10 | 1999-01-21 | Pharmacia & Upjohn S.P.A. | Matrix metalloproteinase inhibitors |
DE19731521A1 (de) | 1997-07-23 | 1999-01-28 | Byk Gulden Lomberg Chem Fab | Budipin bei der Behandlung entzündlicher Erkrankungen des Nervensystems |
AR016551A1 (es) | 1997-07-30 | 2001-07-25 | Smithkline Beecham Corp | Derivados de 2-oxindol, composiciones farmaceuticas que los comprenden y el uso de los mismos para la manufactura de medicamentos |
FR2766822B1 (fr) | 1997-07-30 | 2001-02-23 | Adir | Nouveaux derives de benzimidazole, de benzoxazole et de benzothiazole, leur procede de preparation et les compositions pharmaceutiques qui les contiennent |
CN1265590A (zh) | 1997-07-31 | 2000-09-06 | 赛尔金有限公司 | 取代的链烷异羟肟酸及降低肿瘤坏死因子α水平的方法 |
WO1999006410A1 (en) | 1997-08-04 | 1999-02-11 | Amgen Inc. | Hydroxamic acid substituted fused heterocyclic metalloproteinase inhibitors |
CA2268190A1 (en) | 1997-08-06 | 1999-02-18 | Suntory Limited | 1-aryl-1,8-naphthylidin-4-one derivative as type iv phosphodiesterase inhibitor |
ATE217863T1 (de) | 1997-08-08 | 2002-06-15 | Pfizer Prod Inc | Arylsulfonylaminohydroxamsäurederivate |
WO1999007679A1 (en) | 1997-08-08 | 1999-02-18 | Chiroscience Limited | Peptidyl compounds having mmp and tnf inhibitory activity |
IL121860A0 (en) | 1997-08-14 | 1998-02-22 | Yeda Res & Dev | Interleukin-18 binding proteins their preparation and use |
US5994396A (en) | 1997-08-18 | 1999-11-30 | Centaur Pharmaceuticals, Inc. | Furansulfonic acid derivatives and pharmaceutical compositions containing the same |
CA2300813A1 (en) | 1997-08-21 | 1999-03-04 | Hiroyuki Odaka | Anti-inflammatory agent |
WO1999022760A1 (en) | 1997-11-03 | 1999-05-14 | The Wistar Institute Of Anatomy And Biology | Method and compositions for inhibiting angiogenesis and treating cancer |
US5955476A (en) | 1997-11-18 | 1999-09-21 | Celgene Corporation | Substituted 2-(2,6-dioxo-3-fluoropiperidin-3-yl)-isoindolines and method of reducing inflammatory cytokine levels |
WO1999029865A2 (en) | 1997-12-12 | 1999-06-17 | The Rockefeller University | A protein belonging to the tnf superfamily, nucleic acids encoding same, and methods of use thereof |
AU742768B2 (en) | 1998-01-16 | 2002-01-10 | Renovis, Inc. | Thioether furan nitrone compounds |
EP1049703B1 (en) | 1998-01-20 | 2003-02-12 | Warner-Lambert Company | N-[2-(5-benzyloxycarbonyl-amino-6-oxo-2-(4-fluorophenyl)-1,6-dihydro-1-pyrimidinyl)acetoxyl]-l-aspartic acid aldehyde as an in vivo inhibitor of interleukin-1beta converting enzyme |
DE69926480T2 (de) | 1998-01-23 | 2006-04-13 | Immunex Corp., Thousand Oaks | Acpl dna und polypeptide |
AU737592B2 (en) | 1998-01-23 | 2001-08-23 | Immunex Corporation | Il-18 receptors |
WO1999037818A1 (en) | 1998-01-27 | 1999-07-29 | Millennium Pharmaceuticals, Inc. | Novel molecules of the tnf receptor superfamily and uses therefor |
EP1051407A1 (en) | 1998-01-27 | 2000-11-15 | American Cyanamid Company | 2,3,4,5-tetrahydro-1h-[1,4]-benzodiazepine-3-hydroxamic acids as matrix metalloproteinase inhibitors |
EP1062210B1 (en) | 1998-03-09 | 2005-06-01 | Vertex Pharmaceuticals Incorporated | 1,2-diazepane derivatives as interleukin-1beta converting enzyme inhibitors |
AU755273B2 (en) | 1998-03-16 | 2002-12-05 | Cytovia, Inc. | Dipeptide caspase inhibitors and the use thereof |
IL126024A0 (en) | 1998-03-19 | 1999-05-09 | Yeda Res & Dev | Modulators of the function of receptors of the tnf/ngf receptor family and other proteins |
PT1064298E (pt) | 1998-03-19 | 2009-01-02 | Vertex Pharma | Inibidores de caspasas |
CN1181817C (zh) | 1998-03-20 | 2004-12-29 | 第一三得利制药株式会社 | 以苯基甲苯醌为有效成分的NF-kB抑制剂 |
CA2325741C (en) | 1998-03-26 | 2007-05-08 | Santen Pharmaceutical Co., Ltd. | Urea derivatives having tnf- .alpha. production inhibitory effects |
ATE517916T1 (de) | 1998-05-14 | 2011-08-15 | Immunex Corp | Verfahren zur hemmung der wirkung der osteoklasten |
CA2276216A1 (en) | 1998-06-24 | 1999-12-24 | Kabushiki Kaisha Hayashibara Seibutsu Kagaku Kenkyujo | An artificial peptide capable of neutralizing the biological activity of interleukin-18 |
US6210924B1 (en) | 1998-08-11 | 2001-04-03 | Amgen Inc. | Overexpressing cyclin D 1 in a eukaryotic cell line |
CA2340579A1 (en) | 1998-09-01 | 2000-03-09 | Kabushiki Kaisha Hayashibara Seibutsu Kagaku Kenkyujo | Interleukin 18-binding protein |
PT1114166E (pt) | 1998-09-15 | 2005-08-31 | Pharmexa A S | Metodo para regular negativamente a actividade do ligando da osteoprotegerina |
US6660843B1 (en) * | 1998-10-23 | 2003-12-09 | Amgen Inc. | Modified peptides as therapeutic agents |
KR100856446B1 (ko) * | 1998-12-23 | 2008-09-04 | 화이자 인크. | Ctla-4에 대한 인간 단일클론 항체 |
SI2332976T1 (sl) | 1999-02-03 | 2014-08-29 | Amgen Inc. | Novi polipeptidi, vkljuäśeni v imunskem odgovoru |
AU2880400A (en) | 1999-02-12 | 2000-08-29 | Amgen, Inc. | Tnf-related proteins |
AUPQ314799A0 (en) | 1999-09-29 | 1999-10-21 | University Of Western Australia, The | Bone cell factor |
AU2262501A (en) | 1999-12-16 | 2001-06-25 | Amgen, Inc. | Tnfr/opg-like molecules and uses thereof |
EP1257648B2 (en) † | 2000-02-23 | 2016-09-14 | Amgen Inc. | Antagonistic selective binding agents of osteoprotegerin binding protein |
CA2407956A1 (en) | 2000-05-03 | 2001-11-08 | Amgen Inc. | Modified peptides as therapeutic agents |
US7102050B1 (en) | 2000-05-04 | 2006-09-05 | Exxonmobil Chemical Patents Inc. | Multiple riser reactor |
WO2001091793A1 (en) * | 2000-05-26 | 2001-12-06 | Smithkline Beecham Corporation | Anti-rank ligand monoclonal antibodies useful in treatment of rank ligand mediated disorders |
US7405734B2 (en) * | 2000-07-18 | 2008-07-29 | Silicon Graphics, Inc. | Method and system for presenting three-dimensional computer graphics images using multiple graphics processing units |
DE10039710B4 (de) | 2000-08-14 | 2017-06-22 | United Monolithic Semiconductors Gmbh | Verfahren zur Herstellung passiver Bauelemente auf einem Halbleitersubstrat |
AU2001286586A1 (en) * | 2000-08-18 | 2002-03-04 | University Of Massachusetts Medical Center | Trance regulation of chondrocyte differentiation |
AU2001288342A1 (en) | 2000-08-21 | 2002-03-04 | Smith Kline Beecham Corporation | Anti-rank ligand monoclonal antibodies useful in treatment of rank ligand mediated disorders |
AR032028A1 (es) * | 2001-01-05 | 2003-10-22 | Pfizer | Anticuerpos contra el receptor del factor de crecimiento similar a insulina |
WO2002092016A2 (en) | 2001-05-17 | 2002-11-21 | Immunex Corporation | Therapeutic use of rank antagonists |
MXPA03011270A (es) | 2001-06-06 | 2004-03-18 | Immunex Corp | Uso de antagonistas rank para tratar cancer. |
PL222211B1 (pl) | 2001-06-26 | 2016-07-29 | Amgen Fremont Inc | Przeciwciało przeciwko OPGL, kompozycja je zawierająca, jego zastosowanie i sposób jego wytwarzania, sposób wykrywania poziomu OPGL, kompozycja obejmująca polinukleotydy i komórka gosodarza |
PL375041A1 (en) | 2002-04-05 | 2005-11-14 | Amgen Inc. | Human anti-opgl neutralizing antibodies as selective opgl pathway inhibitors |
JP5782185B2 (ja) | 2012-06-01 | 2015-09-24 | 日本電信電話株式会社 | パケット転送処理方法およびパケット転送処理装置 |
US9300829B2 (en) | 2014-04-04 | 2016-03-29 | Canon Kabushiki Kaisha | Image reading apparatus and correction method thereof |
-
2002
- 2002-06-25 PL PL371915A patent/PL222211B1/pl unknown
- 2002-06-25 AU AU2002320157A patent/AU2002320157C1/en active Active
- 2002-06-25 EP EP10181323.6A patent/EP2270052B8/en not_active Expired - Lifetime
- 2002-06-25 PT PT91569954T patent/PT2087908T/pt unknown
- 2002-06-25 EA EA200400063A patent/EA021242B9/ru active Protection Beyond IP Right Term
- 2002-06-25 TR TR2019/00581T patent/TR201900581T4/tr unknown
- 2002-06-25 WO PCT/US2002/020181 patent/WO2003002713A2/en active Application Filing
- 2002-06-25 EP EP02749660.3A patent/EP1409016B9/en not_active Expired - Lifetime
- 2002-06-25 ES ES02749660T patent/ES2342820T5/es not_active Expired - Lifetime
- 2002-06-25 PT PT10185344T patent/PT2295081T/pt unknown
- 2002-06-25 ES ES10185344T patent/ES2706902T3/es not_active Expired - Lifetime
- 2002-06-25 DE DE60235989T patent/DE60235989D1/de not_active Expired - Lifetime
- 2002-06-25 DK DK02749660.3T patent/DK1409016T4/da active
- 2002-06-25 MX MXPA04000134A patent/MXPA04000134A/es active IP Right Grant
- 2002-06-25 US US10/180,648 patent/US7364736B2/en not_active Expired - Lifetime
- 2002-06-25 AT AT02749660T patent/ATE464068T1/de active
- 2002-06-25 SG SG2011076551A patent/SG2011076551A/en unknown
- 2002-06-25 ME MEP-326/08A patent/MEP32608A/xx unknown
- 2002-06-25 SG SG10201603108QA patent/SG10201603108QA/en unknown
- 2002-06-25 YU YU103003A patent/YU103003A/sh unknown
- 2002-06-25 NZ NZ530765A patent/NZ530765A/en not_active IP Right Cessation
- 2002-06-25 DE DE122010000047C patent/DE122010000047I1/de active Pending
- 2002-06-25 DK DK09156995.4T patent/DK2087908T3/en active
- 2002-06-25 ES ES10181323.6T patent/ES2674888T3/es not_active Expired - Lifetime
- 2002-06-25 KR KR10-2003-7017009A patent/KR20040023630A/ko active Search and Examination
- 2002-06-25 MY MYPI20022368A patent/MY143582A/en unknown
- 2002-06-25 RS RS20120347A patent/RS54274B1/en unknown
- 2002-06-25 SG SG2005081195A patent/SG173211A1/en unknown
- 2002-06-25 EP EP09156995.4A patent/EP2087908B1/en not_active Expired - Lifetime
- 2002-06-25 CA CA2451955A patent/CA2451955C/en not_active Expired - Lifetime
- 2002-06-25 ES ES09156995.4T patent/ES2675735T3/es not_active Expired - Lifetime
- 2002-06-25 CN CN201310052370.5A patent/CN103232539B/zh not_active Expired - Lifetime
- 2002-06-25 KR KR1020107002067A patent/KR101038585B1/ko active Protection Beyond IP Right Term
- 2002-06-25 ME MEP-2008-326A patent/ME00232B/me unknown
- 2002-06-25 TR TR2018/09678T patent/TR201809678T4/tr unknown
- 2002-06-25 NZ NZ616594A patent/NZ616594A/en not_active IP Right Cessation
- 2002-06-25 JP JP2003509075A patent/JP4212470B2/ja not_active Expired - Lifetime
- 2002-06-25 PT PT101813236T patent/PT2270052T/pt unknown
- 2002-06-25 IL IL15951202A patent/IL159512A0/xx unknown
- 2002-06-25 BR BRPI0210579-9 patent/BRPI0210579B8/pt not_active IP Right Cessation
- 2002-06-25 EP EP18202340.8A patent/EP3492100B1/en not_active Expired - Lifetime
- 2002-06-25 CN CNA028166809A patent/CN1547486A/zh active Pending
- 2002-06-25 NO NO20200535A patent/NO345566B1/no not_active IP Right Cessation
- 2002-06-25 EP EP10185344.8A patent/EP2295081B1/en not_active Expired - Lifetime
- 2002-06-25 PT PT02749660T patent/PT1409016E/pt unknown
- 2002-06-25 DK DK10185344.8T patent/DK2295081T3/en active
- 2002-06-25 TR TR2018/09008T patent/TR201809008T4/tr unknown
- 2002-06-25 NZ NZ547695A patent/NZ547695A/en not_active IP Right Cessation
- 2002-06-25 DK DK10181323.6T patent/DK2270052T3/en active
- 2002-06-25 ES ES18202340T patent/ES2907826T3/es not_active Expired - Lifetime
- 2002-06-26 TW TW095103780A patent/TWI326285B/zh not_active IP Right Cessation
- 2002-06-26 TW TW091114055A patent/TWI276443B/zh active
- 2002-06-26 AR ARP020102401A patent/AR034637A1/es active IP Right Grant
-
2003
- 2003-12-22 IL IL159512A patent/IL159512A/en active IP Right Grant
-
2004
- 2004-01-23 ZA ZA200400521A patent/ZA200400521B/xx unknown
- 2004-03-10 NO NO20041018A patent/NO343687B1/no not_active IP Right Cessation
-
2005
- 2005-06-25 NZ NZ581637A patent/NZ581637A/en not_active IP Right Cessation
-
2007
- 2007-10-30 US US11/981,664 patent/US8058418B2/en not_active Expired - Lifetime
-
2008
- 2008-07-04 JP JP2008175541A patent/JP4358282B2/ja not_active Expired - Lifetime
- 2008-12-19 AU AU2008261137A patent/AU2008261137C1/en active Active
-
2009
- 2009-07-08 JP JP2009161406A patent/JP4927910B2/ja not_active Expired - Lifetime
-
2010
- 2010-07-08 CY CY20101100637T patent/CY1110196T1/el unknown
- 2010-11-24 LU LU91757C patent/LU91757I2/fr unknown
- 2010-11-24 CY CY2010016C patent/CY2010016I2/el unknown
- 2010-11-25 FR FR10C0050C patent/FR10C0050I2/fr active Active
-
2011
- 2011-11-14 US US13/296,201 patent/US8409578B2/en not_active Expired - Lifetime
-
2012
- 2012-01-17 JP JP2012006740A patent/JP5065529B2/ja not_active Expired - Lifetime
- 2012-03-23 JP JP2012066632A patent/JP2012153701A/ja not_active Withdrawn
- 2012-07-02 JP JP2012148656A patent/JP5576903B2/ja not_active Expired - Lifetime
-
2013
- 2013-03-14 US US13/831,099 patent/US20140134157A1/en not_active Abandoned
-
2014
- 2014-02-05 HK HK14101098.3A patent/HK1187932A1/xx not_active IP Right Cessation
- 2014-10-19 IL IL235116A patent/IL235116A0/en unknown
- 2014-10-28 JP JP2014218929A patent/JP2015057408A/ja active Pending
- 2014-11-27 JP JP2014239576A patent/JP2015078205A/ja active Pending
-
2015
- 2015-02-12 US US14/621,072 patent/US20150266952A1/en not_active Abandoned
-
2016
- 2016-06-07 JP JP2016113389A patent/JP2016216464A/ja active Pending
- 2016-09-02 US US15/256,194 patent/US20170183417A1/en not_active Abandoned
-
2017
- 2017-12-25 JP JP2017247287A patent/JP2018154614A/ja not_active Ceased
-
2018
- 2018-06-26 CY CY181100655T patent/CY1120656T1/el unknown
- 2018-07-17 CY CY181100747T patent/CY1120658T1/el unknown
-
2019
- 2019-01-21 CY CY20191100079T patent/CY1121151T1/el unknown
- 2019-04-04 NO NO20190456A patent/NO344842B1/no not_active IP Right Cessation
- 2019-06-10 JP JP2019107837A patent/JP2019214563A/ja active Pending
- 2019-11-05 NO NO2019039C patent/NO2019039I1/no unknown
- 2019-12-20 NO NO2019048C patent/NO2019048I1/no unknown
- 2019-12-24 JP JP2019232389A patent/JP2020073518A/ja active Pending
-
2020
- 2020-01-09 US US16/738,751 patent/US20200131271A1/en not_active Abandoned
- 2020-06-18 US US16/905,089 patent/US20200354464A1/en not_active Abandoned
-
2021
- 2021-08-05 JP JP2021128771A patent/JP2022000424A/ja active Pending
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2018154614A (ja) * | 2001-06-26 | 2018-10-04 | アムジェン フレモント インク. | Opglへの抗体 |
Also Published As
Similar Documents
Publication | Publication Date | Title |
---|---|---|
JP5576903B2 (ja) | Opglへの抗体 | |
AU2002320157A1 (en) | Antibodies to OPGL | |
AU2018202668A1 (en) | Antibodies to OPGL |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
A975 | Report on accelerated examination |
Free format text: JAPANESE INTERMEDIATE CODE: A971005 Effective date: 20120502 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20120515 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20120702 |
|
TRDD | Decision of grant or rejection written | ||
A01 | Written decision to grant a patent or to grant a registration (utility model) |
Free format text: JAPANESE INTERMEDIATE CODE: A01 Effective date: 20120807 |
|
A01 | Written decision to grant a patent or to grant a registration (utility model) |
Free format text: JAPANESE INTERMEDIATE CODE: A01 |
|
A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20120809 |
|
R150 | Certificate of patent or registration of utility model |
Ref document number: 5065529 Country of ref document: JP Free format text: JAPANESE INTERMEDIATE CODE: R150 Free format text: JAPANESE INTERMEDIATE CODE: R150 |
|
FPAY | Renewal fee payment (event date is renewal date of database) |
Free format text: PAYMENT UNTIL: 20150817 Year of fee payment: 3 |
|
S531 | Written request for registration of change of domicile |
Free format text: JAPANESE INTERMEDIATE CODE: R313531 |
|
R350 | Written notification of registration of transfer |
Free format text: JAPANESE INTERMEDIATE CODE: R350 |
|
R153 | Grant of patent term extension |
Free format text: JAPANESE INTERMEDIATE CODE: R153 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R153 | Grant of patent term extension |
Free format text: JAPANESE INTERMEDIATE CODE: R153 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R153 | Grant of patent term extension |
Free format text: JAPANESE INTERMEDIATE CODE: R153 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |