PL2890717T3 - Testy i zestawy diagnostyczne do wykrywania receptora folianu - Google Patents

Testy i zestawy diagnostyczne do wykrywania receptora folianu

Info

Publication number
PL2890717T3
PL2890717T3 PL13833526T PL13833526T PL2890717T3 PL 2890717 T3 PL2890717 T3 PL 2890717T3 PL 13833526 T PL13833526 T PL 13833526T PL 13833526 T PL13833526 T PL 13833526T PL 2890717 T3 PL2890717 T3 PL 2890717T3
Authority
PL
Poland
Prior art keywords
kits
detection
diagnostic assays
folate receptor
folate
Prior art date
Application number
PL13833526T
Other languages
English (en)
Polish (pl)
Inventor
Nathan E. TESTA
Christina N. Carrigan
Olga Ab
Daniel Tavares
Beni B. Wolf
Original Assignee
Immunogen, Inc.
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Immunogen, Inc. filed Critical Immunogen, Inc.
Publication of PL2890717T3 publication Critical patent/PL2890717T3/pl

Links

Classifications

    • 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
    • G01N33/574—Immunoassay; Biospecific binding assay; Materials therefor for cancer
    • G01N33/57484—Immunoassay; Biospecific binding assay; Materials therefor for cancer involving compounds serving as markers for tumor, cancer, neoplasia, e.g. cellular determinants, receptors, heat shock/stress proteins, A-protein, oligosaccharides, metabolites
    • G01N33/57492—Immunoassay; Biospecific binding assay; Materials therefor for cancer involving compounds serving as markers for tumor, cancer, neoplasia, e.g. cellular determinants, receptors, heat shock/stress proteins, A-protein, oligosaccharides, metabolites involving compounds localized on the membrane of tumor or cancer cells
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
    • A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
    • A61K47/68—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment
    • A61K47/6835—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment the modifying agent being an antibody or an immunoglobulin bearing at least one antigen-binding site
    • A61K47/6849—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment the modifying agent being an antibody or an immunoglobulin bearing at least one antigen-binding site the antibody targeting a receptor, a cell surface antigen or a cell surface determinant
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • 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
    • 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
    • C07K16/30—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants from tumour cells
    • 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
    • C07K16/30—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants from tumour cells
    • C07K16/3015—Breast
    • 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
    • C07K16/30—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants from tumour cells
    • C07K16/3023—Lung
    • 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
    • C07K16/30—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants from tumour cells
    • C07K16/303—Liver or Pancreas
    • 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
    • C07K16/30—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants from tumour cells
    • C07K16/3069—Reproductive system, e.g. ovaria, uterus, testes, prostate
    • 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
    • G01N33/566—Immunoassay; Biospecific binding assay; Materials therefor using specific carrier or receptor proteins as ligand binding reagents where possible specific carrier or receptor proteins are classified with their target compounds
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K2039/505—Medicinal preparations containing antigens or antibodies comprising antibodies
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/20—Immunoglobulins specific features characterized by taxonomic origin
    • C07K2317/21—Immunoglobulins specific features characterized by taxonomic origin from primates, e.g. man
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/20—Immunoglobulins specific features characterized by taxonomic origin
    • C07K2317/24—Immunoglobulins specific features characterized by taxonomic origin containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/30—Immunoglobulins specific features characterized by aspects of specificity or valency
    • C07K2317/33—Crossreactivity, e.g. for species or epitope, or lack of said crossreactivity
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/70—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
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2333/00—Assays involving biological materials from specific organisms or of a specific nature
    • G01N2333/435—Assays involving biological materials from specific organisms or of a specific nature from animals; from humans
    • G01N2333/705—Assays involving receptors, cell surface antigens or cell surface determinants

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Immunology (AREA)
  • Organic Chemistry (AREA)
  • Molecular Biology (AREA)
  • Cell Biology (AREA)
  • Medicinal Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Biochemistry (AREA)
  • Biomedical Technology (AREA)
  • Urology & Nephrology (AREA)
  • Hematology (AREA)
  • Biophysics (AREA)
  • Genetics & Genomics (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Microbiology (AREA)
  • Oncology (AREA)
  • Pathology (AREA)
  • General Physics & Mathematics (AREA)
  • Physics & Mathematics (AREA)
  • Analytical Chemistry (AREA)
  • Food Science & Technology (AREA)
  • Biotechnology (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Animal Behavior & Ethology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Hospice & Palliative Care (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Epidemiology (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Reproductive Health (AREA)
  • Gynecology & Obstetrics (AREA)
  • Pregnancy & Childbirth (AREA)
  • Peptides Or Proteins (AREA)
PL13833526T 2012-08-31 2013-08-30 Testy i zestawy diagnostyczne do wykrywania receptora folianu PL2890717T3 (pl)

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
US201261695791P 2012-08-31 2012-08-31
US201361756254P 2013-01-24 2013-01-24
EP13833526.0A EP2890717B1 (en) 2012-08-31 2013-08-30 Diagnostic assays and kits for detection of folate receptor 1
PCT/US2013/057682 WO2014036495A2 (en) 2012-08-31 2013-08-30 Diagnostic assays and kits for detection of folate receptor 1

Publications (1)

Publication Number Publication Date
PL2890717T3 true PL2890717T3 (pl) 2020-08-10

Family

ID=50184673

Family Applications (1)

Application Number Title Priority Date Filing Date
PL13833526T PL2890717T3 (pl) 2012-08-31 2013-08-30 Testy i zestawy diagnostyczne do wykrywania receptora folianu

Country Status (27)

Country Link
US (6) US9200073B2 (enExample)
EP (2) EP2890717B1 (enExample)
JP (6) JP6293147B2 (enExample)
KR (4) KR102617499B1 (enExample)
CN (2) CN104755498B (enExample)
AU (4) AU2013308497B2 (enExample)
BR (1) BR112015004229B1 (enExample)
CA (2) CA2883222C (enExample)
CY (1) CY1122907T1 (enExample)
DK (1) DK2890717T3 (enExample)
ES (1) ES2788151T3 (enExample)
HR (1) HRP20200482T1 (enExample)
HU (1) HUE049693T2 (enExample)
IL (4) IL299620A (enExample)
LT (1) LT2890717T (enExample)
ME (1) ME03799B (enExample)
MX (2) MX378788B (enExample)
NZ (2) NZ630433A (enExample)
PL (1) PL2890717T3 (enExample)
PT (1) PT2890717T (enExample)
RS (1) RS60217B1 (enExample)
RU (1) RU2668824C2 (enExample)
SG (2) SG11201500938XA (enExample)
SI (1) SI2890717T1 (enExample)
SM (1) SMT202000158T1 (enExample)
WO (1) WO2014036495A2 (enExample)
ZA (1) ZA201707245B (enExample)

Families Citing this family (27)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP3196212B1 (en) 2010-02-24 2020-06-03 ImmunoGen, Inc. Immunoconjugates comprising a folate receptor 1 antibody
UA113403C2 (xx) 2011-04-01 2017-01-25 Спосіб підвищення ефективності folr1 терапії раку
SMT202000158T1 (it) 2012-08-31 2020-05-08 Immunogen Inc Saggi e kit diagnostici per il rilevamento del recettore dei folati 1
US20160311921A1 (en) * 2013-06-20 2016-10-27 Morphotek ,Inc. Methods for treatment of ovarian cancer
CA2921975C (en) 2013-08-30 2024-02-13 Immunogen, Inc. Antibodies and assays for detection of folate receptor 1
DK3055332T3 (da) * 2013-10-08 2019-12-09 Immunogen Inc Anti-folr1-immunkonjugat-doseringsregimer
WO2015149018A1 (en) * 2014-03-28 2015-10-01 Immunogen, Inc. Anti-folr1 immunoconjugate dosing regimens
US20170247449A1 (en) * 2014-06-06 2017-08-31 Kyowa Hakko Kirin Co., Ltd Therapeutic method and medicament for cancer patients by folr1-targeting drug and an antagonist for folic acid metabolism
EA201791121A1 (ru) * 2014-11-20 2018-04-30 Ф. Хоффманн-Ля Рош Аг Активирующие т-клетки биспецифические антигенсвязывающие молекулы против folri и cd3
US10172875B2 (en) 2015-09-17 2019-01-08 Immunogen, Inc. Therapeutic combinations comprising anti-FOLR1 immunoconjugates
CN105548059B (zh) * 2016-01-29 2018-08-24 福建医科大学 叶酸-牛血清白蛋白-铂铋纳米复合材料
WO2017192863A1 (en) * 2016-05-04 2017-11-09 L.E.A.F. Holdings Group Llc Targeted liposomal gemcitabine compositions and methods thereof
US10822410B2 (en) 2016-11-23 2020-11-03 Eisai R&D Management Co., Ltd. Anti-folate receptor alpha antibodies and uses thereof
CN108982430B (zh) * 2017-05-31 2020-09-29 北京大学 标记细菌菌群样品的试剂盒、方法及应用
EP3679371A4 (en) * 2017-09-05 2021-06-16 Immunogen, Inc. METHOD OF DETECTING FOLATE RECEPTOR 1 IN A PATIENT SAMPLE
US11873335B2 (en) * 2018-03-13 2024-01-16 Phanes Therapeutics, Inc. Anti-folate receptor 1 antibodies and uses thereof
BR112021017046A2 (pt) * 2019-04-12 2021-11-09 Phanes Therapeutics Inc Receptores de antígeno quiméricos antirreceptores de folato 1 humanizados e seus usos
US11396543B2 (en) 2019-04-29 2022-07-26 Immunogen, Inc. Biparatopic FR-α antibodies and immunoconjugates
CN112794911B (zh) * 2021-04-14 2021-08-03 上海偌妥生物科技有限公司 人源化抗叶酸受体1抗体及其应用
WO2022256507A1 (en) * 2021-06-04 2022-12-08 Immunogen, Inc. Treatment of cancer in patients with soluble fr-alpha
CN114163520B (zh) * 2021-11-23 2024-01-30 南京京达生物技术有限公司 一种血源性人IgM抗体纯化介质制备方法
US20250059274A1 (en) 2021-12-24 2025-02-20 Bio-Thera Solutions, Ltd. ANTI-FRa ANTIBODY, AND ANTIBODY-DRUG CONJUGATE AND USE THEREOF
US20250391517A1 (en) * 2022-03-11 2025-12-25 Russell Gary Latimer An optical density measurement and testing device
CN119019546B (zh) * 2022-07-05 2025-09-05 东莞市朋志生物科技有限公司 抗乙型流感病毒抗体、检测乙型流感病毒的试剂和试剂盒
WO2025094146A1 (en) 2023-11-02 2025-05-08 Immunogen Switzerland Gmbh Vasconstrictors for reducing ocular toxicity of antibody-maytansinoid conjugates
CN117700557B (zh) * 2024-02-05 2024-04-30 卡秋(江苏)生物科技有限公司 一种特异性结合叶酸受体α的抗体或抗原结合片段
CN117700556B (zh) * 2024-02-05 2024-04-12 苏州百道医疗科技有限公司 一种抗FRα小鼠单克隆抗体及其应用

Family Cites Families (154)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3645090A (en) 1969-06-19 1972-02-29 Citizen Watch Co Ltd Day-date quick-adjuster for calender timepiece
US3940475A (en) 1970-06-11 1976-02-24 Biological Developments, Inc. Radioimmune method of assaying quantitatively for a hapten
US4588585A (en) 1982-10-19 1986-05-13 Cetus Corporation Human recombinant cysteine depleted interferon-β muteins
US4816567A (en) 1983-04-08 1989-03-28 Genentech, Inc. Recombinant immunoglobin preparations
DE229046T1 (de) 1985-03-30 1987-12-17 Marc Genf/Geneve Ballivet Verfahren zum erhalten von dns, rns, peptiden, polypeptiden oder proteinen durch dns-rekombinant-verfahren.
US4737456A (en) 1985-05-09 1988-04-12 Syntex (U.S.A.) Inc. Reducing interference in ligand-receptor binding assays
US4676980A (en) 1985-09-23 1987-06-30 The United States Of America As Represented By The Secretary Of The Department Of Health And Human Services Target specific cross-linked heteroantibodies
US5618920A (en) 1985-11-01 1997-04-08 Xoma Corporation Modular assembly of antibody genes, antibodies prepared thereby and use
DE3600905A1 (de) 1986-01-15 1987-07-16 Ant Nachrichtentech Verfahren zum dekodieren von binaersignalen sowie viterbi-dekoder und anwendungen
US5681718A (en) 1986-03-14 1997-10-28 Celltech Limited Methods for enhanced production of tissue plasminogen activator in cell culture using alkanoic acids or salts thereof
US5225539A (en) 1986-03-27 1993-07-06 Medical Research Council Recombinant altered antibodies and methods of making altered antibodies
US4946778A (en) 1987-09-21 1990-08-07 Genex Corporation Single polypeptide chain binding molecules
US5763192A (en) 1986-11-20 1998-06-09 Ixsys, Incorporated Process for obtaining DNA, RNA, peptides, polypeptides, or protein, by recombinant DNA technique
WO1989006692A1 (en) 1988-01-12 1989-07-27 Genentech, Inc. Method of treating tumor cells by inhibiting growth factor receptor function
GB8823869D0 (en) 1988-10-12 1988-11-16 Medical Res Council Production of antibodies
GB8826530D0 (en) 1988-11-12 1988-12-14 Ped Capacitors Ltd Electrical capacitors
US20030229208A1 (en) 1988-12-28 2003-12-11 Protein Design Labs, Inc. Humanized immunoglobulins
US5530101A (en) 1988-12-28 1996-06-25 Protein Design Labs, Inc. Humanized immunoglobulins
US5108921A (en) 1989-04-03 1992-04-28 Purdue Research Foundation Method for enhanced transmembrane transport of exogenous molecules
CA2057923A1 (en) 1989-05-16 1990-11-17 William D. Huse Co-expression of heteromeric receptors
CA2016841C (en) 1989-05-16 1999-09-21 William D. Huse A method for producing polymers having a preselected activity
CA2016842A1 (en) 1989-05-16 1990-11-16 Richard A. Lerner Method for tapping the immunological repertoire
EP1690935A3 (en) 1990-01-12 2008-07-30 Abgenix, Inc. Generation of xenogeneic antibodies
US6172197B1 (en) 1991-07-10 2001-01-09 Medical Research Council Methods for producing members of specific binding pairs
GB9015198D0 (en) 1990-07-10 1990-08-29 Brien Caroline J O Binding substance
US6916605B1 (en) 1990-07-10 2005-07-12 Medical Research Council Methods for producing members of specific binding pairs
DE69130647T2 (de) 1990-08-24 1999-05-06 Ixsys, Inc., San Diego, Calif. Verfahren zur herstellung von oligonukleotiden mit regellosen codonen
US5661016A (en) 1990-08-29 1997-08-26 Genpharm International Inc. Transgenic non-human animals capable of producing heterologous antibodies of various isotypes
US5625126A (en) 1990-08-29 1997-04-29 Genpharm International, Inc. Transgenic non-human animals for producing heterologous antibodies
US5633425A (en) 1990-08-29 1997-05-27 Genpharm International, Inc. Transgenic non-human animals capable of producing heterologous antibodies
US5545806A (en) 1990-08-29 1996-08-13 Genpharm International, Inc. Ransgenic non-human animals for producing heterologous antibodies
DK0546073T3 (da) 1990-08-29 1998-02-02 Genpharm Int Frembringelse og anvendelse af transgene, ikke-humane dyr, der er i stand til at danne heterologe antistoffer
WO1992009690A2 (en) 1990-12-03 1992-06-11 Genentech, Inc. Enrichment method for variant proteins with altered binding properties
EP0563296B1 (en) 1990-12-20 1999-03-17 Ixsys, Inc. Optimization of binding proteins
DE69229477T2 (de) 1991-09-23 1999-12-09 Cambridge Antibody Technology Ltd., Melbourn Methoden zur Herstellung humanisierter Antikörper
ES2341666T3 (es) 1991-12-02 2010-06-24 Medimmune Limited Produccion de autoanticuerpos de repertorios de segmentos de anticue rpos expresados en la superficie de fagos.
EP0571613B1 (en) 1991-12-13 2003-09-17 Xoma Corporation Methods and materials for preparation of modified antibody variable domains and therapeutic uses thereof
PT627940E (pt) 1992-03-05 2003-07-31 Univ Texas Utilizacao de imunoconjugados para o diagnostico e/ou terapia de tumores vascularizados
US5965132A (en) 1992-03-05 1999-10-12 Board Of Regents, The University Of Texas System Methods and compositions for targeting the vasculature of solid tumors
US20030148406A1 (en) 1992-03-17 2003-08-07 David John King Multivalent antigen-binding proteins
US5639641A (en) 1992-09-09 1997-06-17 Immunogen Inc. Resurfacing of rodent antibodies
AU6132994A (en) 1993-02-02 1994-08-29 Scripps Research Institute, The Methods for producing antibody libraries using universal or randomized immunoglobulin light chains
EP0714409A1 (en) 1993-06-16 1996-06-05 Celltech Therapeutics Limited Antibodies
US5731168A (en) 1995-03-01 1998-03-24 Genentech, Inc. Method for making heteromultimeric polypeptides
US5641870A (en) 1995-04-20 1997-06-24 Genentech, Inc. Low pH hydrophobic interaction chromatography for antibody purification
DE69637481T2 (de) 1995-04-27 2009-04-09 Amgen Fremont Inc. Aus immunisierten Xenomäusen stammende menschliche Antikörper gegen IL-8
EP0823941A4 (en) 1995-04-28 2001-09-19 Abgenix Inc HUMAN ANTIBODIES DERIVED FROM IMMUNIZED XENO MOUSES
DE69621940T2 (de) 1995-08-18 2003-01-16 Morphosys Ag Protein-/(poly)peptidbibliotheken
US6828422B1 (en) 1995-08-18 2004-12-07 Morphosys Ag Protein/(poly)peptide libraries
WO1997011971A1 (en) 1995-09-28 1997-04-03 Alexion Pharmaceuticals, Inc. Porcine cell interaction proteins
US6331431B1 (en) 1995-11-28 2001-12-18 Ixsys, Inc. Vacuum device and method for isolating periplasmic fraction from cells
US5714352A (en) 1996-03-20 1998-02-03 Xenotech Incorporated Directed switch-mediated DNA recombination
CA2616914C (en) 1996-12-03 2012-05-29 Abgenix, Inc. Egfr-binding antibody
US6596850B1 (en) 1998-01-30 2003-07-22 Ixsys, Incorporated Anti-αv3β3 recombinant human antibodies, nucleic acids encoding same
AU8691398A (en) 1997-08-04 1999-02-22 Ixsys, Incorporated Methods for identifying ligand specific binding molecules
WO2000023082A1 (en) 1998-10-19 2000-04-27 Yeda Research And Development Co. Ltd. Treatment of systemic lupus erythematosus by down-regulating the autoimmune response to autoantigens
US20040031072A1 (en) 1999-05-06 2004-02-12 La Rosa Thomas J. Soy nucleic acid molecules and other molecules associated with transcription plants and uses thereof for plant improvement
WO2001002588A2 (en) 1999-07-02 2001-01-11 Morphosys Ag Generation of specific binding partners binding to (poly)peptides encoded by genomic dna fragments or ests
IT1307309B1 (it) 1999-12-30 2001-10-30 Enea Ente Nuove Tec Peptidi stabilizzanti, polipeptidi ed anticorpi che li comprendono.
US7033594B2 (en) 2000-03-31 2006-04-25 Purdue Research Foundation Method of treatment using ligand-immunogen conjugates
DE10037759A1 (de) 2000-08-03 2002-07-04 Gruenenthal Gmbh Screeningverfahren
CA2438652A1 (en) 2001-02-19 2002-09-06 Merck Patent Gesellschaft Mit Beschraenkter Haftung Method for identification of t-cell epitopes and use for preparing molecules with reeduced immunogenicity
US20030087250A1 (en) 2001-03-14 2003-05-08 Millennium Pharmaceuticals, Inc. Nucleic acid molecules and proteins for the identification, assessment, prevention, and therapy of ovarian cancer
NZ529808A (en) 2001-05-02 2007-02-23 Purdue Research Foundation Treatment and diagnosis of macrophage mediated disease
US7314974B2 (en) 2002-02-21 2008-01-01 Monsanto Technology, Llc Expression of microbial proteins in plants for production of plants with improved properties
EP1486566A4 (en) 2002-03-01 2005-10-12 Japan Enviro Chemicals Ltd FOR BINDING TO FEMALE SEXUAL HORMONES, PROTEINS AND METHOD FOR THE PRODUCTION THEREOF
US7531522B2 (en) 2002-04-22 2009-05-12 Fraunhofer-Gesellschaft Zur Forderung Der Angewandten Forschung E.V. Antibodies, recombinant antibodies, recombinant antibody fragments and fusions mediated plant disease resistance against fungi
US7538195B2 (en) 2002-06-14 2009-05-26 Immunogen Inc. Anti-IGF-I receptor antibody
GB0216648D0 (en) 2002-07-18 2002-08-28 Lonza Biologics Plc Method of expressing recombinant protein in CHO cells
MXPA05004712A (es) 2002-11-07 2005-11-23 Immunogen Inc Anticuerpos anti-cd33 y metodo para tratamiento de leucemia mieloide aguda utilizando los mismos.
AU2003295411A1 (en) 2002-11-07 2004-06-03 Celltech R & D Human monoclonal antibodies to heparanase
EP1481993A1 (en) 2003-05-28 2004-12-01 Xerion Pharmaceuticals AG Modulation of the poliovirus receptor function
US20050255114A1 (en) 2003-04-07 2005-11-17 Nuvelo, Inc. Methods and diagnosis for the treatment of preeclampsia
US20050025763A1 (en) 2003-05-08 2005-02-03 Protein Design Laboratories, Inc. Therapeutic use of anti-CS1 antibodies
CA2897608C (en) 2003-05-09 2018-07-31 Duke University Cd20-specific antibodies and methods employing same
NZ543498A (en) 2003-05-14 2007-06-29 Immunogen Inc A conjugate comprising an antibody chemically coupled to a maytansinoid
US7276497B2 (en) 2003-05-20 2007-10-02 Immunogen Inc. Cytotoxic agents comprising new maytansinoids
CA2530393A1 (en) 2003-07-02 2005-01-13 Genentech, Inc. Compositions and methods for the diagnosis and treatment of tumor
US7622112B2 (en) 2003-12-05 2009-11-24 Jody Berry Anti-SARS monoclonal antibodies
EP2316857A1 (en) 2004-02-12 2011-05-04 Morphotek, Inc. Monoclonal antibodies that specifically bind to folate receptor alpha
US20080187954A1 (en) 2004-03-10 2008-08-07 Lonza Ltd. Method For Producing Antibodies
WO2005103716A2 (en) 2004-04-27 2005-11-03 Galapagos N.V. Methods, agents, and compound screening assays for inducing differentiation of undifferentiated mammalian cells into osteoblasts
KR20070072510A (ko) 2004-08-30 2007-07-04 론자 바이올로직스 피엘씨 항체 정제를 위한 친화도- 및 이온 교환- 크로마토그래피
US7776869B2 (en) 2004-10-18 2010-08-17 Amgen Inc. Heteroaryl-substituted alkyne compounds and method of use
EP2465872A3 (en) 2004-10-25 2012-12-19 Merck Sharp & Dohme Corporation Anti-ADDL antibodies and uses thereof
WO2007044043A2 (en) 2004-12-21 2007-04-19 Monsanto Technology, Llc Transgenic plants with enhanced agronomic traits
WO2006073941A2 (en) 2004-12-31 2006-07-13 Genentech, Inc. Polypeptides that bind br3 and uses thereof
US7700738B2 (en) 2005-01-27 2010-04-20 The Regents Of The University Of California Therapeutic monoclonal antibodies that neutralize botulinum neurotoxins
ES2432091T5 (es) 2005-03-25 2022-03-18 Gitr Inc Moléculas de unión GITR y usos de las mismas
US7608413B1 (en) 2005-03-25 2009-10-27 Celera Corporation Kidney disease targets and uses thereof
US20090081710A1 (en) 2005-03-30 2009-03-26 Purdue Research Foundation Method for Cancer Prognosis Using Cellular Folate Vitamin Receptor Quantification
US20060239910A1 (en) 2005-04-22 2006-10-26 Morphotek Inc. Antibodies with immune effector activity and that internalize in folate receptor alpha-positive cells
US7786266B2 (en) 2005-05-12 2010-08-31 Oncotherapy Science, Inc. Methods for damaging cells using effector function of anti-DSC2 antibody
KR101273829B1 (ko) 2005-05-20 2013-06-11 론자 바이올로직스 피엘씨 포유류 숙주 세포에서의 재조합 항체의 고-수준 발현
CA2609731A1 (en) 2005-05-24 2006-11-30 Avestha Gengraine Technologies Pvt Ltd. A method for the production of a monoclonal antibody to cd20 for the treatment of b-cell lymphoma
JP5175723B2 (ja) 2005-07-05 2013-04-03 パーデュー・リサーチ・ファウンデーション 単球介在性疾患を治療するための組成物の調製
US7521195B1 (en) 2005-07-21 2009-04-21 Celera Corporation Lung disease targets and uses thereof
CA2619725C (en) 2005-08-18 2016-06-07 Ramot At Tel Aviv University Ltd. Single chain antibodies against beta-amyloid peptide
CA2621363C (en) 2005-09-13 2015-07-07 National Research Council Of Canada Methods and compositions for modulating tumor cell activity
US20070099251A1 (en) 2005-10-17 2007-05-03 Institute For Systems Biology Tissue-and serum-derived glycoproteins and methods of their use
EP1790664A1 (en) 2005-11-24 2007-05-30 Ganymed Pharmaceuticals AG Monoclonal antibodies against claudin-18 for treatment of cancer
KR101526934B1 (ko) 2005-12-20 2015-06-26 에스비아이 바이오테크 가부시키가이샤 항-ｉｌｔ7 항체
WO2007143561A1 (en) 2006-06-01 2007-12-13 Mayo Foundation For Medical Education And Research Immunity to folate receptors
WO2007147265A1 (en) 2006-06-23 2007-12-27 Alethia Biotherapeutics Inc. Polynucleotides and polypeptide sequences involved in cancer
US7910702B2 (en) 2006-07-28 2011-03-22 The Governors Of The University Of Alberta Recombinant antibodies to sclerotinia antigens
CA2660286A1 (en) 2006-08-09 2008-02-21 Homestead Clinical Corporation Organ-specific proteins and methods of their use
US20090182955A1 (en) 2006-09-08 2009-07-16 Rao Cherukuri Application configuration across client devices of a local system
EP1900752A1 (en) * 2006-09-15 2008-03-19 DOMPE' pha.r.ma s.p.a. Human anti-folate receptor alpha antibodies and antibody fragments for the radioimmunotherapy of ovarian carcinoma
AU2007312367B2 (en) 2006-10-12 2012-09-06 Chugai Seiyaku Kabushiki Kaisha Diagnosis and treatment of cancer using anti-EREG antibody
CN101663322A (zh) 2006-12-14 2010-03-03 株式会社未来创药研究所 抗紧密连接蛋白3单克隆抗体以及使用该抗体的癌症的治疗和诊断
CN103709249B (zh) 2006-12-20 2016-02-24 Mmr全球公司 抗体及其制备和使用方法
US20080227704A1 (en) 2006-12-21 2008-09-18 Kamens Joanne S CXCL13 binding proteins
US7691980B2 (en) 2007-01-09 2010-04-06 Bio-Rad Laboratories, Inc. Enhanced capacity and purification of antibodies by mixed mode chromatography in the presence of aqueous-soluble nonionic organic polymers
EP2609934A1 (en) 2007-02-16 2013-07-03 KTB Tumorforschungsgesellschaft mbH Receptor And Antigen Targeted Prodrug
US20100104626A1 (en) 2007-02-16 2010-04-29 Endocyte, Inc. Methods and compositions for treating and diagnosing kidney disease
WO2008145136A1 (en) 2007-05-30 2008-12-04 Aarhus Universitet Stat3 inactivation by inhibition of the folate receptor pathway
EP3569251A1 (en) 2007-06-25 2019-11-20 Endocyte, Inc. Conjugates containing hydrophilic spacer linkers
CN101139613B (zh) 2007-08-01 2011-06-08 姜荣锡 抗肿瘤二元多肽及其应用与制备方法
WO2009080759A1 (en) 2007-12-21 2009-07-02 Novartis Ag Organic compounds
EP4282428A3 (en) 2008-01-11 2024-03-20 The University of Tokyo Anti-cldn6 antibody
EP2238154B1 (en) 2008-01-18 2015-09-16 Bio-Rad Laboratories, Inc. Enhanced purification of phosphorylated and non-phosphorylated biomolecules by apatite chromatography
JP5470817B2 (ja) 2008-03-10 2014-04-16 日産自動車株式会社 電池用電極およびこれを用いた電池、並びにその製造方法
RU2568976C2 (ru) 2008-04-21 2015-11-20 Свапсол Корп. Преобразование сероводорода в водород
WO2009132081A2 (en) 2008-04-24 2009-10-29 The Research Foundation Of State University Of New York Monoclonal antibody-based targeting of folate receptors
UA108598C2 (xx) 2008-04-30 2015-05-25 Високоефективні кон'югати та гідрофільні зшиваючі агенти (лінкери)
KR101892411B1 (ko) 2008-04-30 2018-08-27 이뮤노젠 아이엔씨 가교제 및 그 용도
US8383351B2 (en) 2008-06-11 2013-02-26 Oxford Brookes University Antibody to inhibin/ activin β-B subunit
US20100069298A1 (en) * 2008-09-16 2010-03-18 Robert Penny Methods for Detecting Overexpression of SPARC and Therapeutic and Diagnostic Methods Relating to Same
NZ592255A (en) 2008-09-17 2013-07-26 Endocyte Inc Folate receptor binding conjugates of antifolates
WO2010033913A1 (en) 2008-09-22 2010-03-25 Icb International, Inc. Antibodies, analogs and uses thereof
CN101440130B (zh) 2008-11-21 2011-07-27 中国人民解放军第四军医大学 一种抗人IL-13Rα2单克隆抗体的重链和轻链的可变区
ES2557914T3 (es) 2009-03-24 2016-01-29 Biocept, Inc. Dispositivos y métodos de captura y análisis de células
WO2011010652A1 (ja) * 2009-07-23 2011-01-27 株式会社資生堂 油中水型乳化化粧料
DK2462161T3 (en) 2009-08-06 2017-06-06 Immunas Pharma Inc Antibodies specifically binding to A-beta oligomers and their use
WO2011100398A1 (en) 2010-02-10 2011-08-18 Immunogen, Inc. Cd20 antibodies and uses thereof
EP3196212B1 (en) 2010-02-24 2020-06-03 ImmunoGen, Inc. Immunoconjugates comprising a folate receptor 1 antibody
RU2013122843A (ru) * 2010-10-20 2014-11-27 Морфотек, Инк. Гликоформы антитела против фолатного рецептора альфа
MX368394B (es) * 2010-11-05 2019-10-01 Eisai Inc Receptor alfa de folato como marcador de diagnostico y pronostico para canceres que expresan receptor alfa de folato.
KR102272828B1 (ko) 2011-03-29 2021-07-05 이뮤노젠 아이엔씨 일-단계 방법에 의한 메이탄시노이드 항체 접합체의 제조
EA025786B1 (ru) 2011-03-29 2017-01-30 Иммуноджен, Инк. Способ производства конъюгатов с улучшенной гомогенностью
UA113403C2 (xx) 2011-04-01 2017-01-25 Спосіб підвищення ефективності folr1 терапії раку
US20120282282A1 (en) 2011-04-04 2012-11-08 Immunogen, Inc. Methods for Decreasing Ocular Toxicity of Antibody Drug Conjugates
JP6220333B2 (ja) * 2011-07-15 2017-10-25 エーザイ・アール・アンド・ディー・マネジメント株式会社 抗葉酸受容体アルファ抗体およびその使用
SMT202000158T1 (it) 2012-08-31 2020-05-08 Immunogen Inc Saggi e kit diagnostici per il rilevamento del recettore dei folati 1
CA2893378A1 (en) 2012-12-07 2014-06-12 Kyowa Hakko Kirin Co., Ltd. Anti-folr1 antibody
JP6136279B2 (ja) 2013-01-15 2017-05-31 株式会社ジェイテクト 転がり軸受装置
TWI503850B (zh) 2013-03-22 2015-10-11 Polytronics Technology Corp 過電流保護元件
CN119185571A (zh) 2013-05-14 2024-12-27 伊缪诺金公司 抗folr1免疫缀合物给药方案
CA2921975C (en) 2013-08-30 2024-02-13 Immunogen, Inc. Antibodies and assays for detection of folate receptor 1
TWI510996B (zh) 2013-10-03 2015-12-01 Acer Inc 控制觸控面板的方法以及使用該方法的可攜式電腦
DK3055332T3 (da) 2013-10-08 2019-12-09 Immunogen Inc Anti-folr1-immunkonjugat-doseringsregimer
WO2015149018A1 (en) 2014-03-28 2015-10-01 Immunogen, Inc. Anti-folr1 immunoconjugate dosing regimens
US10172875B2 (en) 2015-09-17 2019-01-08 Immunogen, Inc. Therapeutic combinations comprising anti-FOLR1 immunoconjugates
US9816280B1 (en) 2016-11-02 2017-11-14 Matthew Reitnauer Portable floor

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