TR201802659T4 - Folr1 kanser terapisinin etkinliğini arttırmak için yöntemler. - Google Patents

Folr1 kanser terapisinin etkinliğini arttırmak için yöntemler. Download PDF

Info

Publication number
TR201802659T4
TR201802659T4 TR2018/02659T TR201802659T TR201802659T4 TR 201802659 T4 TR201802659 T4 TR 201802659T4 TR 2018/02659 T TR2018/02659 T TR 2018/02659T TR 201802659 T TR201802659 T TR 201802659T TR 201802659 T4 TR201802659 T4 TR 201802659T4
Authority
TR
Turkey
Prior art keywords
folr1
immunoconjugate
antibody
cancer
amino acid
Prior art date
Application number
TR2018/02659T
Other languages
English (en)
Inventor
N Carrigan Christina
R Whiteman Kathleen
Payne Gillian
Ladd Sharron
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 TR201802659T4 publication Critical patent/TR201802659T4/tr

Links

Classifications

    • 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
    • A61K47/6851—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 determinant of a tumour cell
    • 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
    • A61K47/6801—Drug-antibody or immunoglobulin conjugates defined by the pharmacologically or therapeutically active agent
    • A61K47/6803—Drugs conjugated to an antibody or immunoglobulin, e.g. cisplatin-antibody conjugates
    • A61K47/68033—Drugs conjugated to an antibody or immunoglobulin, e.g. cisplatin-antibody conjugates the drug being a maytansine
    • 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
    • A61K47/6801—Drug-antibody or immunoglobulin conjugates defined by the pharmacologically or therapeutically active agent
    • A61K47/6803—Drugs conjugated to an antibody or immunoglobulin, e.g. cisplatin-antibody conjugates
    • A61K47/6807—Drugs conjugated to an antibody or immunoglobulin, e.g. cisplatin-antibody conjugates the drug or compound being a sugar, nucleoside, nucleotide, nucleic acid, e.g. RNA antisense
    • A61K47/6809—Antibiotics, e.g. antitumor antibiotics anthracyclins, adriamycin, doxorubicin or daunomycin
    • 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
    • A61K47/6801—Drug-antibody or immunoglobulin conjugates defined by the pharmacologically or therapeutically active agent
    • A61K47/6803—Drugs conjugated to an antibody or immunoglobulin, e.g. cisplatin-antibody conjugates
    • A61K47/6811—Drugs conjugated to an antibody or immunoglobulin, e.g. cisplatin-antibody conjugates the drug being a protein or peptide, e.g. transferrin or bleomycin
    • A61K47/6817—Toxins
    • 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
    • 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
    • A61K47/6851—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 determinant of a tumour cell
    • A61K47/6869—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 determinant of a tumour cell the tumour determinant being from a cell of the reproductive system: ovaria, uterus, testes, prostate
    • 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
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • 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
    • 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
    • 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
    • A61K39/395—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2800/00—Detection or diagnosis of diseases
    • G01N2800/52—Predicting or monitoring the response to treatment, e.g. for selection of therapy based on assay results in personalised medicine; Prognosis
    • 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
    • G01N33/577—Immunoassay; Biospecific binding assay; Materials therefor involving monoclonal antibodies binding reaction mechanisms characterised by the use of monoclonal antibodies; monoclonal antibodies per se are classified with their corresponding antigens

Abstract

İnsan folat reseptörü 1'i hedef alan kanser terapilerinin başarısını iyileştirmek için yöntemler sağlanır. İlaveten, yöntemlerde yararlı olan reaktifleri içeren kitler sağlanır.

Description

TARIFNAME FOLR1 KANSER TERAPISININ ETKINLIGINI ARTTIRMAK içiN YÖNTEMLER ILGILI BASVURULARA ÇAPRAZ-REFERANS Bu basvuru, 1 Nisan 2011'de dosyalanan, U.S. Provizyonel Basvuru No. 61/471,007'nin yararhüalep etmektedir.
BULUSUN ALT-YAPISI Bulusun Sahasi Bulusun alani genel olarak, insan folat reseptörü 1'in (FOLR1'in) asirii-iekspresyonu ile karakterize edilen kanserlerin tedavisinin etkinligini arttlrlma ile ilgilidir. Daha spesifik olarak, bulus kansere yatkn olan veya kanser tansîalmüs olan hastalarin daha etkili tedavisi ile ilgilidir, burada tümör hücreleri bir FOLR1 antagonisti, örnegin, bir FOLR1 immünokonjugat] ile bir gen ekspresyon analiz ile belirlendigi üzere FOLR1'i asEEeksprese eder.
Teknigin AIt-YapLsLI Kanser, yalnizca Amerika Birlesik Devletleri'nde her ym kanser tanLsLlalms bir milyonun üstünde insan ve 500.000 ölüm ile, gelismis dünyada ölümün önde gelen nedenlerinden biridir. Toplamda, her 3 insanda 1'inden fazlasnini yasamlar l boyunca kanserin bir kaç formunu gelistirecegi tahmin edilir. -Meme, akciger, kolorektal ve prostat- olan dördünün tüm yeni olgularm yarßmdan fazlaslia sebebiyet verdigi 200'den fazla farklEkanser tipi vardE (Jemal et al., 2003, Cancer Ayri [zamanda Folat Reseptörü-alfa veya Folat Baglama Proteini olarak da bilinen Folat Reseptörü 1 (FOLR1), hücrelerin plazma membran: üzerinde eksprese edilen bir N-glikosile edilmis proteindir. FOLR1, folik asit için ve bir kaç indirgenmis folik asit türevi için yüksek bir afiniteye sahiptir. FOLR1, fizyolojik folat n, 5- methitetrahidrofolatin, hücrelerin iç kISmlnia aktar m na arac Ilk eder.
FOLR1, ovaryan kanserlerin büyük çogunlugunda ve çok sayida uterin, endometriyal, pankreatik, renal, akciger ve meme kanserinde asnîeksprese edilirken, normal dokularda FOLR1 ekspresyonu böbrek proksimal tübüllerindeki, akcigerin alveoler pnömositlerindeki, idrar kesesindeki, testislerdeki, koroid pleksustaki ve tiroitteki epitelyal hücrelerin apikal membranEile shllandmii bu ekspresyon paterni, bunu FOLR1'e yönlendirilmis kanser terapisi için arzu edilebilir bir hedef haline getirir.
Ovaryan kanser ilerlemis evreye kadar tipik olarak asemptomatik olugundan, buna sikllkla geç bir evrede tani koyulur ve güncel olarak mevcut prosedürler, tipik olarak cerrahi tümör ç karma ameliyat nidan sonra kemoterapötik ilaçlar, ile tedavi edildiginde bu kötü prognoza sahiptir (von Gruenigen V et al., Cancer 112: 2221- için daha etkili terapötiklere yönelik karslanmamg asikar bir ihtiyaç vard I.
BULUSUN KISA AÇIKLAMASI Mevcut bulus, tümör dokusunda FOLR1'in dinamik bir ekspresyon aralLgLnim kesfine ve arttirilmis FOLR1 ekspresyon düzeyleri olan tümörlerin anti-FOLR1 antikorlari iveya anti-FOLR1 immünokonjugatlari ile tedaviye daha çok yanit verdigi kesfine dayanir. Mevcut bulus avantajlîbir sekilde, terapötik ajanlar] yani, anti- FOLR1 antikorlarnjveya anti-FOLR1 immünokonjugatlari] bir arttîlttmß FOLR1 ekspresyon düzeyine sahip oldugu bulunan hastalara uygulama ile tedaviye yarim vermenin daha büyük bir olasmgma sahip olan hastalarh tedavisine izin verir.
Mevcut bulus, bir süjede kanser terapisinde kullanJInasj için bir anti-Folat reseptörü 1 (FOLR1) antikoru veya anti-FOLR1 immünokonjugatEolup, burada söz konusu süjeden aanian bir kanser örneginde FOLR1 geninin veya proteininin bir arttiriilmis ekspresyonu, bir veya birden fazla referans örnekte boyama yogunluguna veya boyama tekdüzeligine k yasla bir FOLR1 eksprese eden kanser örneginde boyama yogunlugunu veya boyama tekdüzeligini ayint eden bir saptama yöntemi kullanilarak saptanmistin, burada bir anti-FOLR1 antikoru veya anti- FOLR1 immünokonjugatîle kanser terapisinin etkinligi bu yolla arttnirnistm; burada, kanser terapisinde kullantlmasEiçin anti-FOLR1 antikoru asagîilakileri (i) SEO lD NO: 3 amino asit dizisini içeren bir ag& zincir degisken alan: (huM ve SEO ID NO: 4 amino asit dizisini içeren bir hafif zincir degisken alan JhuMov veya (ii) SEQ ID NO: 3 amino asit dizisini içeren bir agn zincir degisken alani (huMov19 vHC) ve SEO ID NO: 5 amino asit dizisini içeren bir hafif zincir degisken alan (huMov19 vLCv1.60); ve burada kanser terapisinde kullanilmas iiçin anti-FOLR1 immünokonjugati ibir anti- FOLR1 antikoru, bir baglayÜFi ve bir sitotoksin içerir, burada anti-FOLR1 immünokonjugatnn anti-FOLR1 antikoru asag Illakileri içerir: (i) SEQ lD NO: 3 amino asit dizisini içeren bir ag& zincir degisken alan: (huM ve SEO ID NO: 4 amino asit dizisini içeren bir hafif zincir degisken alan 1huMov veya (ii) SEQ ID NO: 3 amino asit dizisini içeren bir ag] zincir degisken alan: (huMov19 vHC) ve SEO ID NO: 5 amino asit dizisini içeren bir hafif zincir degisken alan (huMov19 vLCv1.60).
Bulusun ilave uygulamalarTlZ ila 17 arasmidaki istemler ile tanlîtnlanm Mevcut bulus, bir Folat Reseptörü 1'i (FOLR1) hedef alan anti-kanser terapötigine olumlu bir sekilde yantt verme egiliminde olan bir süjeyi tanmnlamak için bir yöntemi tarif eder, yöntem süjeden elde edilen bir doku örneginde FOLR1 ekspresyonunu saptamayjçerir.
Mevcut bulus aerca, bir kanser terapisinin etkililiginin olasiLgJJiJarttLrmak için bir yöntemi de tarif eder, yöntem bir FOLRi'i hedef alan anti-kanser terapötiginin bir terapötik olarak etkili dozunu bir süjeye uygulamayi içerir, burada süjeden elde edilen bir doku örneginde FOLR1 ekspresyonunun arttiii Id gi bulunmustur.
Mevcut bulus ayrßa, bir düsük-dozlu kanser tedavisinin etkililigini tahmin etmek için bir yöntem de tarif eder, yöntem bir FOLR1'i hedef alan anti-kanser terapötiginin bir terapötik olarak etkili dozunu bir süjeye uygulamayüiçerir, burada söz konusu süjenin bir örnek içinde arttltlîmß FOLR1 ekspresyonuna sahip oldugu bulunmustur.
Bir uygulamada, yöntemler ovaryan karsinoma, küçük hücreli-olmayan akciger adenokarsinomuna (bronsiyoloalveoler karsinom dahil), renal karsinomlara ve endometriyal karsinomlara yöneliktir.
Bir uygulamada, FOLR1 ekspresyonunun kapsam i ve tekdüzeligi immünohistokimya (IHC), akis sitometrisi veya nükleik asit hibridizasyonu ile saptanl. Bir baska uygulamada, FOLR1 ekspresyonunun düzeyi immünohistokimya ile saptanE. IHC'nin sîlayEE olmayan örnekleri, FOLR1'in çesitlilik gösteren düzeylerini ayît eden IHC yöntemlerini ve kalibre edilmis IHC yöntemlerini, örnegin, burada tarif edilenleri, içerir. FOLR1 ekspresyonu, bunlarla smmltkalmamak kaydg/Ia, burada tarif edilen skorlama yöntemlerini içeren, uygun bir skorlama sistemi kullanilarak skorlanabilir. Örnegin, FOLR1 ekspresyonu, boyama yogunlugu için O'Lni en düsük boyama yogunlugu düzeyi oldugu ve 3+'nm en yüksek boyama yogunlugu düzeyi oldugu 0, 1, 2, 3 ve 3+ olan bir araligi iiçeren bir kalibre edilmis IHC yöntemi kullanilarak skorlanabilir. Alternatif veya ilave olarak, FOLR1 ekspresyonu fokal (boyanmis hücrelerin

Claims (1)

  1. ISTEMLER Bir süjede kanser terapisinde kullanrimasüçin bir anti-Folat reseptörü 1 (FOLR1) antikoru veya anti-FOLR1 immünokonjugatjolup, burada söz konusu süjeden alman bir kanser örneginde FOLR1 geninin veya proteininin bir arttiIÜ'mS ekspresyonu, bir veya birden fazla referans örnekte boyama yogunluguna veya boyama tekdüzeligine kß/asla bir FOLR1 eksprese eden kanser örneginde boyama yogunlugunu veya boyama tekdüzeligini ayEt eden bir saptama yöntemi kullanilarak saptanmßtl, burada bir anti-FOLR1 antikoru veya anti-FOLR1 immünokonjugatdile kanser terapisinin etkinligi bu yolla artt nilm st ri; burada, kanser terapisinde kullanilmasil için anti-FOLR1 antikoru asagidakileri içerir: (i) SEQ ID NO: 3 amino asit dizisini içeren bir agi? zincir degisken alanj(huM ve SEO ID NO: 4 amino asit dizisini içeren bir hafif zincir degisken alan E(huMov veya (ii) SEQ lD NO: 3 amino asit dizisini içeren bir agi zincir degisken alanj(huMov19 vHC) ve SEQ ID NO: 5 amino asit dizisini Içeren bir hafif zincir degisken alanj(huMov19 vLCv1.60); ve burada kanser terapisinde kullanitmasüiçin anti-FOLR1 immünokonjugatjbir anti- FOLR1 antikoru, bir baglaycdve bir sitotoksin içerir, burada anti- FOLR1 immünokonjugatiniini anti-FOLR1 antikoru asagidakileri içerir: (i) SEQ ID NO: 3 amino asit dizisini içeren bir agiTi zincir degisken alanü(huMov19 vHC) ve SEQ ID NO: 4 amino asit dizisini içeren bir hafif zincir degisken alan: (huM veya (ii) SEQ ID NO: 3 amino asit dizisini içeren bir agI zincir degisken alanD(huMov19 vHC) ve SEO ID NO: 5 amino asit dizisini içeren bir hafif zincir degisken alan: (huM. 2. istem 1'e göre kullanilmasi için anti-FOLR1 antikoru veya anti-FOLR1 immünokonjugat iolup, burada kanser terapisinde kullanilmasl için anti- FOLR1 antikorunun hafif zincir degisken alanWSEQ ID NO: 5 amino asit dizisini (huMov19 vLCv1.60) içerir, özel olarak burada kanser terapisinde kullanÜinasEiçin anti-FOLR1 antikoru (i) Amerikan Tipi Kültür Koleksiyonu (ATCC) ile PTA-10772 olarak depolanan plazmid tarafmdan sifrelenen ag] zincirin amino asit dizisi ile aynÜamino asit dizisini içeren bir ag& zincir ve (il) ATCC ile FTA-10774 olarak depolanan plazmid tarafmdan sifrelenen hafif zincirin amino asit dizisi ile aynîamino asit dizisini içeren bir hafif zincir içenrve burada, anti-FOLR1 immünokonjugatinln anti-FOLR1 antikorunun hafif zincir degisken alani, SEO ID NO: 5 amino asit dizisini (huMov19 vLCv1.60) içerir, özel olarak burada kanser terapisinde kullanilmasi liçin anti-FOLR1 immünokonjugat n ni anti-FOLR1 antikoru (i) Amerikan Tipi Kültür Koleksiyonu (ATCC) ile PTA-10772 olarak depolanan plazmid taraf-ndan sifrelenen agi zincirin amino asit dizisi ile ayri :amino asit dizisini içeren bir agm zincir ve (ii) ATCC ile PTA-10774 olarak depolanan plazmid tarafDdan sifrelenen hafif zincirin amino asit dizisi ile ayn :amino asit dizisini içeren bir hafif zincir içerir. . istem 'l'e göre kullanm'nasEiçin anti-FOLR1 antikoru veya anti-FOLR1 immünokonjugati olup, burada saptama yöntemi immünohistokimyadn (IHC), özel olarak burada söz konusu lHC, FOLR1 ekspresyonunun farkli düzeylerini ay rlt edebilen kalibre edilmis IHC'dir. . istem 3'e göre kullanümasEiçin anti-FOLR1 antikoru veya anti-FOLR1 immünokonjugatjolup, burada saptama yöntemi fokal FOLR1 dagmhnlia (boyanmS hücrelerin < %25'i), heterojen FOLR1 dagilijnmia (boyanmß hücrelerin %25-75'i) veya homojen FOLR1 dagÜJInma (boyanmS hücrelerin > %75'i) sahip olan örnekler için boyama tekdüzeliginin bir araltgmü'iretir. . istem 1'e göre kullanilmasLiçin anti-FOLR1 antikoru veya anti-FOLR1 immünokonjugat iolup, burada saptama yöntemi bir referans örnegine kiyasla bir FOLR1 eksprese eden kanser örneginde boyama yogunlugunu ve boyama tekdüzeligini ay nt eder. . istem 5'e göre kullanmnasEiçin anti-FOLR1 antikoru veya anti-FOLR1 immünokonjugatjolup, burada kanser örnegi lHC ile, özellikle bir formalin ile fikse edilmis parafine gömülmüs örnek üzerinde lHC ile, FOLR1 ekspresyonu için heterojen veya homojen olan bir boyama tekdüzeligine ve 1, 2, 3 veya 3+ olan bir boyama yogunlugu skoruna sahiptir. . Istem 5'e göre kullanilmasLiçin anti-FOLR1 antikoru veya anti-FOLR1 immünokonjugat i olup, burada kanser örnegi lHC yoluyla FOLR1 ekspresyonu için 1 veya daha büyük olan bir boyama yogunlugu skoruna sahiptir, özel olarak a) burada kanser örnegi FOLR1 ekspresyonu için heterojen olan bir b) burada kanser örnegi FOLR1 ekspresyonu için homojen olan bir 0) burada kanser örneginin hücrelerinin %25-75'i FOLR1 ekspresyonu için boyanE; veya d) burada kanser örneginin hücrelerinin %75'inden fazlasjFOLR1 ekspresyonu için boyanLr. . Istem 7'ye göre kullan [masi liçin anti-FOLR1 antikoru veya anti-FOLR1 immünokonjugat? olup, burada kanser örnegi lHC yoluyla FOLR1 ekspresyonu için 2 veya daha büyük olan bir boyama yogunluguna sahiptir, özel olarak a) burada kanser örnegi FOLR1 ekspresyonu için heterojen olan bir b) burada kanser örnegi FOLR1 ekspresyonu için homojen olan bir 0) burada kanser örneginin hücrelerinin %25-75'i FOLR1 d) burada kanser örneginin hücrelerinin %75'inden fazlas IFOLR1 ekspresyonu için boyanir. istem 1'e göre kullanmnasEiçin anti-FOLR1 antikoru veya anti-FOLR1 immünokonjugatj olup, burada IHC manüel olarak veya bir otomatiklestirilmis sistem kullan [[arak gerçeklestirilir. 10. Istem 1'e göre kullanJInasüiçin anti-FOLR1 antikoru veya anti-FOLRl immünokonjugatj olup, burada söz konusu referans örnek bir pozitif referans örnektir veya bir negatif referans örnektir, özel olarak burada söz konusu referans örnek hücreler, hücre peletleri veya doku içerir. istem 1'e göre kullan [masi liçin anti-FOLR1 antikoru veya anti-FOLR1 immünokonjugat iolup, burada saptama yöntemi FOLRl ekspresyonunu antikor BN3.2 ile saptamayîçerir. 12. Istem 1'e göre kullanJInasüiçin anti-FOLRl antikoru veya anti-FOLR1 immünokonjugatjolup, burada süje asag Iakilerden olusan gruptan seçilen bir kansere sahiptir: ovaryan kanser, endometriyal kanser, peritoneumun kanseri veya akciger kanseri. 13. Istemler 1 ila 12'den herhangi birine göre kullanLlmasJiçin anti-FOLRl antikoru veya anti-FOLR1 immünokonjugati olup, burada anti-FOLR1 immünokonjugat nl ni baglay cs iasagidakilerden olusan gruptan seçilir: bir yarriabilir baglayoîi bir yariamayan baglayor, bir hidrofilik baglayicrve bir dikarboksilik asit temelli baglayß: özellikle, burada söz konusu baglaymj asaglakilerden olusan gruptan seçilir: N-süksinimidil 4-(2-piridilditiyo)pentanoat (SPP): N-süksinimidil 4-(2- piridilditiy0)-2-sülfopentanoat (sülfo-SPP); N-süksinimidil 4-(2- piridilditiyo)bütanoat (SPDB); N-süksinimidil 4-(2-piridilditiyo)-2- sülfobütanoat (sülfo-SPDB); N-süksinimidil 4-(maleimidometil) siklohekzankarboksilat (SMCC): N-sülfosüksinimidil 4-(maleimidometil) siklohekzankarboksilat (sülfoSMCC); N-süksinimidiI-4-(iyodoasetil)- aminobenzoat (SIAB) ve N-süksinimidiI-[(N-maleimidopropiyonamido)- tetraetilenglikol] ester (NHS-PEG4-maleimid). 14. istem 13'e göre kullanmnasEiçin, anti-FOLR1 antikoru veya anti-FOLR1 immünokonjugatjolup, burada anti-FOLR1 immünokonjugatîîiji baglayEBj N-süksinimidil 4-(2-piridilditiyo)-2 sülfobütanoatti (sülfo-SPDB'dir). 15. Istem 13'e göre kullanÜInasEiçin, anti-FOLR1 antikoru veya anti-FOLR1 immünokonjugatjolup, burada anti-FOLR1 immünokonjugatmm sitotoksik ajan Jasag Ldakilerden olusan gruptan seçilir: bir maytansinoid, maytansinoid analogu, benzodiazepin, taksoid, CC-1065, CC-1065 analogu, duokarmisin, duokarmisin analogu, kaliseamisin, dolastatin, dolastatin analogu, auristatin, tomaymisin türevi ve Ieptomisin türevi veya ajan ni bir ön-ilac ,{ özellikle, burada söz konusu sitotoksik ajan bir maytansinoiddir, özellikle, burada söz konusu sitotoksik ajan, N(2')-deasetiI-N(2')-(3- merkapto-1-oksopropil)-maytansindir (DM1) veya N(2')-deasetiI-N(2')-(4- merkapto-4-metil-1-oksopentiI)-maytansindir (DM4). 16. Istem 15'e göre kullanEIîmasEiçin, anti-FOLR1 antikoru veya anti-FOLR1 immünokonjugatjolup, burada anti-FOLR1 immünokonjugatmm sitotoksik ajan 3 N(2')-deasetiI-N(2')-(4-merkapto-4-metil-1-oksopentil)-maytansindir 17. Istem 15'e göre kullanilmasj için, anti-FOLR1 antikoru veya anti-FOLR1 immünokonjugatîolup, burada anti-FOLR1 immünokonjugatnmi baglaymêî N-süksinimidil 4-(2-piridilditiyo)-2 sülfobütanoatt] (sülfo-SPDB) ve burada anti-FOLR1 immünokonjugatmm sitotoksik ajan: N(2')-deasetiI-N(2')-(4- merkapto-4-metil-1-oksopentiI)-maytansindir (DM4).
TR2018/02659T 2011-04-01 2012-03-30 Folr1 kanser terapisinin etkinliğini arttırmak için yöntemler. TR201802659T4 (tr)

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
US201161471007P 2011-04-01 2011-04-01

Publications (1)

Publication Number Publication Date
TR201802659T4 true TR201802659T4 (tr) 2018-03-21

Family

ID=46932392

Family Applications (1)

Application Number Title Priority Date Filing Date
TR2018/02659T TR201802659T4 (tr) 2011-04-01 2012-03-30 Folr1 kanser terapisinin etkinliğini arttırmak için yöntemler.

Country Status (29)

Country Link
US (4) US8709432B2 (tr)
EP (4) EP3318273B1 (tr)
JP (6) JP6018621B2 (tr)
KR (6) KR20240017965A (tr)
CN (3) CN114441757A (tr)
AU (4) AU2012236219B2 (tr)
BR (1) BR112013025415B1 (tr)
CA (2) CA2831426C (tr)
CY (1) CY1119960T1 (tr)
DK (1) DK2694106T3 (tr)
EA (2) EA028805B1 (tr)
ES (2) ES2661466T3 (tr)
HK (1) HK1254759A1 (tr)
HR (1) HRP20180358T1 (tr)
HU (1) HUE036172T2 (tr)
IL (5) IL281714B2 (tr)
LT (1) LT2694106T (tr)
ME (1) ME03025B (tr)
MX (3) MX340640B (tr)
MY (2) MY186591A (tr)
NO (1) NO2893540T3 (tr)
PL (1) PL2694106T3 (tr)
PT (1) PT2694106T (tr)
RS (1) RS56916B1 (tr)
SG (2) SG193514A1 (tr)
SI (1) SI2694106T1 (tr)
TR (1) TR201802659T4 (tr)
UA (2) UA113403C2 (tr)
WO (1) WO2012135675A2 (tr)

Families Citing this family (42)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20110166319A1 (en) * 2005-02-11 2011-07-07 Immunogen, Inc. Process for preparing purified drug conjugates
AU2006283726C1 (en) 2005-08-24 2015-05-07 Immunogen, Inc. Process for preparing maytansinoid antibody conjugates
ES2726945T3 (es) 2009-06-03 2019-10-10 Immunogen Inc Métodos de conjugación
TW202348631A (zh) 2010-02-24 2023-12-16 美商免疫遺傳股份有限公司 葉酸受體１抗體類和免疫共軛物類及彼等之用途
ME03353B (me) 2011-03-29 2019-10-20 Immunogen Inc Priprema konjugata antitela i majtanzinoida jednostepenim postupkom
HUE036172T2 (hu) 2011-04-01 2018-06-28 Immunogen Inc Eljárások a hatékonyság növelésére a FOLR1 rákkezelésénél
NZ726258A (en) 2012-08-31 2019-07-26 Immunogen Inc Antibodies and uses thereof to detect folate receptor 1
NZ707091A (en) 2012-10-04 2018-12-21 Immunogen Inc Use of a pvdf membrane to purify cell-binding agent cytotoxic agent conjugates
US9353150B2 (en) 2012-12-04 2016-05-31 Massachusetts Institute Of Technology Substituted pyrazino[1′,2′:1 ,5]pyrrolo[2,3-b]-indole-1,4-diones for cancer treatment
ES2691794T3 (es) 2012-12-07 2018-11-28 Kyowa Hakko Kirin Co., Ltd. Anticuerpo anti-FOLR1
JP6482471B2 (ja) 2012-12-21 2019-03-13 バイオアライアンス コマンディテール フェンノートシャップ 親水性の自壊性リンカー及びそのコンジュゲート
US20140302037A1 (en) * 2013-03-15 2014-10-09 Amgen Inc. BISPECIFIC-Fc MOLECULES
MX2015015735A (es) * 2013-05-14 2016-03-31 Immunogen Inc Regimenes de dosificacion de inmunoconjugado anti-receptor en folato 1 (folr1).
KR102585409B1 (ko) 2013-08-30 2023-10-05 이뮤노젠 아이엔씨 엽산 수용체 1의 검출을 위한 항체 및 분석
NZ718766A (en) * 2013-10-08 2020-02-28 Immunogen Inc Anti-folr1 immunoconjugate dosing regimens
WO2015149018A1 (en) * 2014-03-28 2015-10-01 Immunogen, Inc. Anti-folr1 immunoconjugate dosing regimens
US9950077B2 (en) 2014-06-20 2018-04-24 Bioalliance C.V. Anti-folate receptor alpha (FRA) antibody-drug conjugates and methods of using thereof
KR102626976B1 (ko) 2014-09-02 2024-01-18 이뮤노젠 아이엔씨 항체 약물 컨쥬게이트 조성물의 제형화 방법
JP2017527562A (ja) 2014-09-03 2017-09-21 イミュノジェン・インコーポレーテッド 細胞毒性ベンゾジアゼピン誘導体
ES2815353T3 (es) 2014-09-03 2021-03-29 Immunogen Inc Derivados de benzodiazepina citotóxicos
BR112017010324A2 (pt) 2014-11-20 2018-05-15 F. Hoffmann-La Roche Ag método para tratar ou retardar a progressão de um câncer em um indivíduo, moléculas, métodos para aumentar a função imune em um indivíduo e para selecionar um paciente para tratamento, kits, composição farmacêutica e usos de uma combinação de uma molécula
KR20180059430A (ko) * 2015-07-30 2018-06-04 익스프레션 패톨로지, 인크. 최적의 암 치료를 위한 FR-α 및 GART 단백질의 정량화
EP3349796A4 (en) 2015-09-17 2019-05-29 ImmunoGen, Inc. THERAPEUTIC COMBINATIONS COMPRISING ANTI-FOLR1 IMMUNOCONJUGATES
JP2019501139A (ja) 2015-11-25 2019-01-17 イミュノジェン・インコーポレーテッド 医薬製剤及びその使用
US10472422B2 (en) 2016-01-08 2019-11-12 Abgenomics International Inc. Tetravalent anti-PSGL-1 antibodies and uses thereof
US10918627B2 (en) 2016-05-11 2021-02-16 Massachusetts Institute Of Technology Convergent and enantioselective total synthesis of Communesin analogs
EP3518943A4 (en) 2016-09-28 2020-04-22 Atossa Therapeutics, Inc. METHOD FOR ADAPTIVE CELL THERAPY
JP7106560B2 (ja) 2017-02-28 2022-07-26 イミュノジェン・インコーポレーテッド 自己犠牲型ペプチドリンカーを有するメイタンシノイド誘導体及びそのコンジュゲート
WO2018195243A1 (en) 2017-04-20 2018-10-25 Immunogen, Inc. Cytotoxic benzodiazepine derivatives and conjugates thereof
IT201700087291A1 (it) * 2017-07-28 2019-01-28 Fondazione St Italiano Tecnologia Metodo di imaging di un campione biologico e relativa sonda
US10640508B2 (en) 2017-10-13 2020-05-05 Massachusetts Institute Of Technology Diazene directed modular synthesis of compounds with quaternary carbon centers
WO2019133652A1 (en) 2017-12-28 2019-07-04 Immunogen, Inc. Benzodiazepine derivatives
CN115925952A (zh) * 2018-03-13 2023-04-07 东莞凡恩世生物医药有限公司 抗叶酸受体1抗体及其用途
SG11202109569RA (en) 2019-03-21 2021-10-28 Immunogen Inc Methods of preparing cell-binding agent-drug conjugates
CN113661172A (zh) 2019-03-29 2021-11-16 伊缪诺金公司 用于抑制异常细胞生长或治疗增生性疾病的细胞毒性双苯并二氮杂䓬衍生物及其与细胞结合剂的缀合物
LT3958977T (lt) 2019-04-26 2023-12-27 Immunogen, Inc. Kamptotecino dariniai
SG11202111109UA (en) 2019-04-29 2021-11-29 Immunogen Inc Biparatopic fr-alpha antibodies and immunoconjugates
EP3980127A1 (en) * 2019-06-06 2022-04-13 Mythic Therapeutics, Inc. Antigen-binding protein constructs and uses thereof
CN111579798A (zh) * 2020-05-29 2020-08-25 深圳市锦欣医疗科技创新中心有限公司 一种评估子宫内膜容受性的试剂盒及其使用方法
CN117730098A (zh) * 2021-06-04 2024-03-19 伊缪诺金公司 治疗具有可溶性FR-α的患者的癌症
WO2023170216A1 (en) * 2022-03-11 2023-09-14 Astrazeneca Ab A SCORING METHOD FOR AN ANTI-FRα ANTIBODY-DRUG CONJUGATE THERAPY
CN117741149A (zh) * 2024-02-19 2024-03-22 卡秋(江苏)生物科技有限公司 一种用于卵巢癌细胞叶酸受体α的检测试剂盒及其应用

Family Cites Families (115)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
NL154598B (nl) 1970-11-10 1977-09-15 Organon Nv Werkwijze voor het aantonen en bepalen van laagmoleculire verbindingen en van eiwitten die deze verbindingen specifiek kunnen binden, alsmede testverpakking.
US3817837A (en) 1971-05-14 1974-06-18 Syva Corp Enzyme amplification assay
US3939350A (en) 1974-04-29 1976-02-17 Board Of Trustees Of The Leland Stanford Junior University Fluorescent immunoassay employing total reflection for activation
US3996345A (en) 1974-08-12 1976-12-07 Syva Company Fluorescence quenching with immunological pairs in immunoassays
US4275149A (en) 1978-11-24 1981-06-23 Syva Company Macromolecular environment control in specific receptor assays
US4277437A (en) 1978-04-05 1981-07-07 Syva Company Kit for carrying out chemically induced fluorescence immunoassay
US4366241A (en) 1980-08-07 1982-12-28 Syva Company Concentrating zone method in heterogeneous immunoassays
US4563304A (en) 1981-02-27 1986-01-07 Pharmacia Fine Chemicals Ab Pyridine compounds modifying proteins, polypeptides or polysaccharides
US4957939A (en) 1981-07-24 1990-09-18 Schering Aktiengesellschaft Sterile pharmaceutical compositions of gadolinium chelates useful enhancing NMR imaging
US4472509A (en) 1982-06-07 1984-09-18 Gansow Otto A Metal chelate conjugated monoclonal antibodies
US4938948A (en) 1985-10-07 1990-07-03 Cetus Corporation Method for imaging breast tumors using labeled monoclonal anti-human breast cancer antibodies
WO1989006692A1 (en) 1988-01-12 1989-07-27 Genentech, Inc. Method of treating tumor cells by inhibiting growth factor receptor function
US20040049014A1 (en) 1988-12-28 2004-03-11 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
JPH049249A (ja) 1990-04-27 1992-01-14 Kusuda:Kk 塗型剤吹き付け機
US6916605B1 (en) 1990-07-10 2005-07-12 Medical Research Council Methods for producing members of specific binding pairs
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
EP0627940B1 (en) 1992-03-05 2003-05-07 Board of Regents, The University of Texas System Use of immunoconjugates for the diagnosis and/or therapy of vascularized tumors
US20030148406A1 (en) 1992-03-17 2003-08-07 David John King Multivalent antigen-binding proteins
JPH08511420A (ja) 1993-06-16 1996-12-03 セルテック・セラピューテイクス・リミテッド 抗 体
AU7378096A (en) 1995-09-28 1997-04-17 Alexion Pharmaceuticals, Inc. Porcine cell interaction proteins
US6596850B1 (en) 1998-01-30 2003-07-22 Ixsys, Incorporated Anti-αv3β3 recombinant human antibodies, nucleic acids encoding same
CA2354862A1 (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
IT1307309B1 (it) 1999-12-30 2001-10-30 Enea Ente Nuove Tec Peptidi stabilizzanti, polipeptidi ed anticorpi che li comprendono.
WO2001074382A1 (en) 2000-03-31 2001-10-11 Purdue Research Foundation Method of treatment using ligand-immunogen conjugates
DE10037759A1 (de) 2000-08-03 2002-07-04 Gruenenthal Gmbh Screeningverfahren
EP1998266A3 (en) 2001-02-19 2009-02-11 Merck Patent GmbH Method for identification of T-cell epitopes and use for preparing molecules with reduced 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
MXPA03010035A (es) 2001-05-02 2004-06-30 Purdue Research Foundation Tratamiento y diagnostico de enfermedades mediadas por macrofagos.
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
WO2004043989A2 (en) 2002-11-07 2004-05-27 Medarex, Inc. 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
WO2005000901A2 (en) 2003-05-09 2005-01-06 Duke University Cd20-specific antibodies and methods of employing same
KR101424624B1 (ko) 2003-05-14 2014-07-31 이뮤노젠 아이엔씨 약물 콘쥬게이트 조성물
US8088387B2 (en) 2003-10-10 2012-01-03 Immunogen Inc. Method of targeting specific cell populations using cell-binding agent maytansinoid conjugates linked via a non-cleavable linker, said conjugates, and methods of making said conjugates
US7276497B2 (en) 2003-05-20 2007-10-02 Immunogen Inc. Cytotoxic agents comprising new maytansinoids
JP2008500949A (ja) 2003-07-02 2008-01-17 ジェネンテック・インコーポレーテッド 腫瘍の診断と治療のための組成物と方法
US7622112B2 (en) 2003-12-05 2009-11-24 Jody Berry Anti-SARS monoclonal antibodies
AU2005214331B2 (en) 2004-02-12 2011-09-15 Eisai, Inc. Monoclonal antibodies that specifically bind to folate receptor alpha
MXPA06012162A (es) 2004-04-27 2007-03-30 Galapagos Nv Metodos, agentes y ensayos de seleccion de compuestos para inducir diferenciacion de celulas de mamifero no diferenciadas, en osteoblastos.
US7241598B2 (en) 2004-06-29 2007-07-10 The Chinese University Of Hong Kong Frame-shifting PCR for germline immunoglobulin genes retrieval and antibody engineering
WO2006055178A2 (en) 2004-10-25 2006-05-26 Merck & Co., Inc. Anti-addl antibodies and uses thereof
CA2875402C (en) 2004-12-21 2021-09-28 Monsanto Technology Llc Transgenic plants with enhanced agronomic traits
JP2008526205A (ja) 2004-12-31 2008-07-24 ジェネンテック・インコーポレーテッド Ｂｒ３に結合するポリペプチド及びその使用
WO2007094754A2 (en) 2005-01-27 2007-08-23 The Regents Of The University Of Califordnia Therapeutic monoclonal antibodies that neutralize botulinum neurotoxins
EP1866339B8 (en) 2005-03-25 2021-12-01 GITR, Inc. Gitr binding molecules and uses therefor
US7608413B1 (en) 2005-03-25 2009-10-27 Celera Corporation Kidney disease targets and uses thereof
EP1864133B1 (en) 2005-03-30 2010-03-10 Purdue Research Foundation Method for breastcancer prognosis using cellular folate vitamin receptor quantification
CA2607444C (en) 2005-04-22 2015-03-10 Morphotek, Inc. Antibodies with immune effector activity and that internalize in folate receptor alpha-positive cells
JP2008539693A (ja) 2005-05-12 2008-11-20 オンコセラピー・サイエンス株式会社 抗ｄｓｃ２抗体のエフェクター機能を用いて細胞を障害する方法
KR101273829B1 (ko) 2005-05-20 2013-06-11 론자 바이올로직스 피엘씨 포유류 숙주 세포에서의 재조합 항체의 고-수준 발현
JP2009508467A (ja) 2005-05-24 2009-03-05 アベスタゲン リミテッド Ｂ細胞リンパ腫の治療のためのｃｄ２０に対するモノクローナル抗体を生成する方法
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
US8124076B2 (en) 2005-08-18 2012-02-28 Ramot At Tel Aviv University Ltd. Single chain antibodies against β-amyloid peptide
ES2543341T3 (es) 2005-09-13 2015-08-18 National Research Council Of Canada Métodos y composiciones para modular la actividad de células tumorales
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
DK2913343T3 (en) 2005-12-20 2018-11-26 Sbi Biotech Co Ltd Anti-ILT7 antibody
WO2007143561A1 (en) 2006-06-01 2007-12-13 Mayo Foundation For Medical Education And Research Immunity to folate receptors
CA2655933C (en) 2006-06-23 2014-09-09 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
US8586006B2 (en) 2006-08-09 2013-11-19 Institute For Systems Biology Organ-specific proteins and methods of their use
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
EP1900533A1 (de) 2006-09-16 2008-03-19 J. Zimmer Maschinenbau Gesellschaft m.b.H. Vorrichtung zum Auftragen von Substanz auf flächige Substrate
AU2007312367B2 (en) 2006-10-12 2012-09-06 Chugai Seiyaku Kabushiki Kaisha Diagnosis and treatment of cancer using anti-EREG antibody
EP2103628A4 (en) 2006-12-14 2012-02-22 Forerunner Pharma Res Co Ltd MONOCLONAL ANTIBODY ANTI-CLAUDIN 3, AND TREATMENT AND DIAGNOSIS OF CANCER USING SUCH ANTIBODY
US8465741B2 (en) 2006-12-20 2013-06-18 Mmrglobal, Inc. Antibodies and methods for making and using them
US20080227704A1 (en) 2006-12-21 2008-09-18 Kamens Joanne S CXCL13 binding proteins
EP2606911A1 (en) 2007-02-16 2013-06-26 KTB Tumorforschungsgesellschaft mbH Receptor And Antigen Targeted Prodrug
WO2008101231A2 (en) 2007-02-16 2008-08-21 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
RU2523909C2 (ru) 2007-06-25 2014-07-27 Эндосайт, Инк. Конъюгаты, содержащие гидрофильные спейсеры линкеров
AU2008282863A1 (en) 2007-07-31 2009-02-05 Merck Sharp & Dohme Corp. IGF-1R specific antibodies useful in the detection and diagnosis of cellular proliferative disorders
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
US20090087849A1 (en) 2007-09-06 2009-04-02 Tripath Imaging, Inc. Nucleic acid-based methods and compositions for the detection of ovarian cancer
PT2227549E (pt) 2007-12-21 2015-10-08 Novartis Ag Sistema de seleção para cultura de células eucarióticas com base num gene de recetor de folato ligado à membrana
EP3064512B1 (en) 2008-01-11 2023-08-30 The University of Tokyo Anti-cldn6 antibody
WO2009132081A2 (en) 2008-04-24 2009-10-29 The Research Foundation Of State University Of New York Monoclonal antibody-based targeting of folate receptors
SG189817A1 (en) 2008-04-30 2013-05-31 Immunogen Inc Potent conjugates and hydrophilic linkers
US8236319B2 (en) 2008-04-30 2012-08-07 Immunogen, Inc. Cross-linkers and their uses
US8383351B2 (en) 2008-06-11 2013-02-26 Oxford Brookes University Antibody to inhibin/ activin β-B subunit
NZ592255A (en) 2008-09-17 2013-07-26 Endocyte Inc Folate receptor binding conjugates of antifolates
US20100092470A1 (en) 2008-09-22 2010-04-15 Icb International, Inc. Antibodies, analogs and uses thereof
JP2012509058A (ja) 2008-11-20 2012-04-19 オンコセラピー・サイエンス株式会社 前立腺癌を診断または治療するための方法
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
WO2010111388A2 (en) 2009-03-24 2010-09-30 Biocept, Inc. Devices and methods of cell capture and analysis
EP2462161B1 (en) * 2009-08-06 2017-03-08 Immunas Pharma, Inc. Antibodies that specifically bind to a beta oligomers and use thereof
WO2011032296A1 (en) 2009-09-21 2011-03-24 Mount Sinai Hospital Methods and compositions for the diagnosis and treatment of thyroid cancer
TW201129383A (en) 2010-02-10 2011-09-01 Immunogen Inc CD20 antibodies and uses thereof
TW202348631A (zh) * 2010-02-24 2023-12-16 美商免疫遺傳股份有限公司 葉酸受體１抗體類和免疫共軛物類及彼等之用途
SG10201701933XA (en) 2010-11-05 2017-05-30 Morphotek Inc Folate receptor alpha as a diagnostic and prognostic marker for folate receptor alpha-expressing cancers
KR20140019415A (ko) * 2011-03-29 2014-02-14 이뮤노젠 아이엔씨 향상된 균질성의 접합체를 제조하기 위한 방법
ME03353B (me) * 2011-03-29 2019-10-20 Immunogen Inc Priprema konjugata antitela i majtanzinoida jednostepenim postupkom
WO2012135517A2 (en) * 2011-03-29 2012-10-04 Immunogen, Inc. Preparation of maytansinoid antibody conjugates by a one-step process
HUE036172T2 (hu) * 2011-04-01 2018-06-28 Immunogen Inc Eljárások a hatékonyság növelésére a FOLR1 rákkezelésénél
US20120282282A1 (en) 2011-04-04 2012-11-08 Immunogen, Inc. Methods for Decreasing Ocular Toxicity of Antibody Drug Conjugates
WO2012145112A2 (en) 2011-04-18 2012-10-26 Immunogen, Inc. Novel maytansinoid derivatives with sulfoxide linker
ES2663556T3 (es) 2011-07-15 2018-04-13 Eisai R&D Management Co., Ltd. Anticuerpos frente al receptor alfa del folato y usos de los mismos
NZ726258A (en) 2012-08-31 2019-07-26 Immunogen Inc Antibodies and uses thereof to detect folate receptor 1
WO2014055842A1 (en) 2012-10-04 2014-04-10 Immunogen, Inc. Process for preparing stable antibody maytansinoid conjugates
MX2015015735A (es) 2013-05-14 2016-03-31 Immunogen Inc Regimenes de dosificacion de inmunoconjugado anti-receptor en folato 1 (folr1).
KR102585409B1 (ko) 2013-08-30 2023-10-05 이뮤노젠 아이엔씨 엽산 수용체 1의 검출을 위한 항체 및 분석
NZ718766A (en) * 2013-10-08 2020-02-28 Immunogen Inc Anti-folr1 immunoconjugate dosing regimens
WO2015149018A1 (en) * 2014-03-28 2015-10-01 Immunogen, Inc. Anti-folr1 immunoconjugate dosing regimens
KR20200028510A (ko) 2014-07-01 2020-03-16 익스프레션 패톨로지, 인크. 화학요법 표적에 대한 srm 검정
KR102626976B1 (ko) 2014-09-02 2024-01-18 이뮤노젠 아이엔씨 항체 약물 컨쥬게이트 조성물의 제형화 방법
EP3349796A4 (en) 2015-09-17 2019-05-29 ImmunoGen, Inc. THERAPEUTIC COMBINATIONS COMPRISING ANTI-FOLR1 IMMUNOCONJUGATES
JP7106560B2 (ja) 2017-02-28 2022-07-26 イミュノジェン・インコーポレーテッド 自己犠牲型ペプチドリンカーを有するメイタンシノイド誘導体及びそのコンジュゲート
US20180333503A1 (en) 2017-05-16 2018-11-22 Immunogen, Inc. Anti-folr1 immunoconjugates and anti-pd-1 antibody combinations

Also Published As

Publication number Publication date
MX340640B (es) 2016-07-19
AU2017202927A1 (en) 2017-05-25
JP2019194257A (ja) 2019-11-07
JP2021006547A (ja) 2021-01-21
EP2694106A4 (en) 2015-04-08
BR112013025415A2 (pt) 2016-12-27
IL281714B2 (en) 2023-11-01
EP4309671A3 (en) 2024-03-20
AU2012236219B2 (en) 2017-02-23
IL281714A (en) 2021-05-31
KR20210088746A (ko) 2021-07-14
US8709432B2 (en) 2014-04-29
CN103747802B (zh) 2018-06-01
AU2021206842A1 (en) 2021-08-12
EP3318273B1 (en) 2019-08-21
IL228538B (en) 2018-12-31
UA125636C2 (uk) 2022-05-11
US20180200383A1 (en) 2018-07-19
NO2893540T3 (tr) 2018-06-09
ME03025B (me) 2018-10-20
SG10201602553VA (en) 2016-05-30
SG193514A1 (en) 2013-10-30
LT2694106T (lt) 2018-04-25
JP2022062219A (ja) 2022-04-19
DK2694106T3 (en) 2018-03-05
EA201791843A2 (ru) 2017-12-29
CA3182262A1 (en) 2012-10-04
JP2014513068A (ja) 2014-05-29
KR101982317B1 (ko) 2019-05-27
HK1254759A1 (zh) 2019-07-26
AU2019202611A1 (en) 2019-05-02
KR102101160B1 (ko) 2020-04-16
PL2694106T3 (pl) 2018-06-29
JP6018621B2 (ja) 2016-11-02
KR20140027969A (ko) 2014-03-07
MX2019010336A (es) 2019-10-14
AU2012236219A1 (en) 2013-10-10
BR112013025415B1 (pt) 2021-03-16
NZ711375A (en) 2017-02-24
SI2694106T1 (en) 2018-04-30
EP3318273A1 (en) 2018-05-09
MY186591A (en) 2021-07-29
US20140363453A1 (en) 2014-12-11
EA201391351A1 (ru) 2014-11-28
EA028805B1 (ru) 2018-01-31
EA201791843A3 (ru) 2018-05-31
EP3636279A1 (en) 2020-04-15
HRP20180358T1 (hr) 2018-04-06
JP2016147901A (ja) 2016-08-18
AU2017202927B2 (en) 2019-01-17
IL228538A0 (en) 2013-12-31
JP2018118997A (ja) 2018-08-02
WO2012135675A2 (en) 2012-10-04
ES2661466T3 (es) 2018-04-02
IL281714B1 (en) 2023-07-01
RS56916B1 (sr) 2018-05-31
MX2013011098A (es) 2013-12-16
UA113403C2 (xx) 2017-01-25
KR20200039843A (ko) 2020-04-16
CA2831426C (en) 2023-02-21
KR20230013283A (ko) 2023-01-26
PT2694106T (pt) 2018-03-05
AU2019202611B2 (en) 2021-05-06
CN114441757A (zh) 2022-05-06
EP2694106A2 (en) 2014-02-12
IL262956B (en) 2020-04-30
CN108743965A (zh) 2018-11-06
KR20240017965A (ko) 2024-02-08
CN103747802A (zh) 2014-04-23
KR102489185B1 (ko) 2023-01-17
ES2965109T3 (es) 2024-04-11
EP2694106B1 (en) 2017-12-13
WO2012135675A3 (en) 2012-12-06
KR20190058696A (ko) 2019-05-29
IL262956A (en) 2018-12-31
NZ615742A (en) 2015-09-25
US20120282175A1 (en) 2012-11-08
HUE036172T2 (hu) 2018-06-28
MY180894A (en) 2020-12-11
CY1119960T1 (el) 2018-12-12
US11135305B2 (en) 2021-10-05
US20220143208A1 (en) 2022-05-12
EP4309671A2 (en) 2024-01-24
CA2831426A1 (en) 2012-10-04
IL303208A (en) 2023-07-01
EP3636279B1 (en) 2023-09-13
IL273614A (en) 2020-05-31
MX346555B (es) 2017-03-24

Similar Documents

Publication Publication Date Title
TR201802659T4 (tr) Folr1 kanser terapisinin etkinliğini arttırmak için yöntemler.
Skidmore et al. ARX788, a site-specific anti-HER2 antibody–drug conjugate, demonstrates potent and selective activity in HER2-low and T-DM1–resistant breast and gastric cancers
Sano et al. An antibody-drug conjugate directed to the ALK receptor demonstrates efficacy in preclinical models of neuroblastoma
Li et al. A biparatopic HER2-targeting antibody-drug conjugate induces tumor regression in primary models refractory to or ineligible for HER2-targeted therapy
Ab et al. IMGN853, a folate receptor-α (FRα)–targeting antibody–drug conjugate, exhibits potent targeted antitumor activity against FRα-expressing tumors
Morrison et al. Development of ASG-15ME, a novel antibody–drug conjugate targeting SLITRK6, a new urothelial cancer biomarker
Barok et al. ARX788, a novel anti-HER2 antibody-drug conjugate, shows anti-tumor effects in preclinical models of trastuzumab emtansine-resistant HER2-positive breast cancer and gastric cancer
Hamblett et al. AMG 595, an anti-EGFRvIII antibody–drug conjugate, induces potent antitumor activity against EGFRvIII-expressing glioblastoma
Barok et al. Trastuzumab-DM1 is highly effective in preclinical models of HER2-positive gastric cancer
Black et al. SYD985, a novel duocarmycin-based HER2-targeting antibody–drug conjugate, shows antitumor activity in uterine serous carcinoma with HER2/Neu expression
Decary et al. Preclinical activity of SAR408701: a novel anti-CEACAM5–maytansinoid antibody–drug conjugate for the treatment of CEACAM5-positive epithelial tumors
English et al. T‐DM1, a novel antibody–drug conjugate, is highly effective against primary HER2 overexpressing uterine serous carcinoma in vitro and in vivo
JP2014513068A5 (tr)
Nguyen et al. Preclinical efficacy and safety assessment of an antibody–drug conjugate targeting the c-RET proto-oncogene for breast carcinoma
CN104364651A (zh) 用于增加基于cd37的疗法的功效的方法
Perrone et al. Sacituzumab govitecan, an antibody‐drug conjugate targeting trophoblast cell‐surface antigen 2, shows cytotoxic activity against poorly differentiated endometrial adenocarcinomas in vitro and in vivo
Woitok et al. Comparison of a mouse and a novel human scFv-SNAP-auristatin F drug conjugate with potent activity against EGFR-overexpressing human solid tumor cells
Wali et al. Identification and validation of a novel biologics target in triple negative breast cancer
Kinneer et al. Design and preclinical evaluation of a novel B7-H4–directed antibody–drug conjugate, AZD8205, alone and in combination with the PARP1-selective inhibitor AZD5305
Prince et al. Evaluation of fluorescence‐guided surgery agents in a murine model of soft tissue fibrosarcoma
Li et al. Monomethyl auristatin E-conjugated anti-EGFR antibody inhibits the growth of human EGFR-positive non-small cell lung cancer
Schunselaar et al. Trophoblast glycoprotein is associated with a favorable outcome for mesothelioma and a target for antibody drug conjugates
Zhu et al. Rational Design and Systemic Appraisal of an EGFR-Targeting Antibody–Drug Conjugate LR-DM1 for Pancreatic Cancer
Lofgren et al. Pan-cancer distribution of cleaved cell-surface amphiregulin, the target of the GMF-1A3 antibody drug conjugate
Zhu et al. Development of potent antibody drug conjugates against ICAM1+ cancer cells in preclinical models of cholangiocarcinoma