ES2531629T3 - Anticuerpos anti-MIF - Google Patents

Anticuerpos anti-MIF Download PDF

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Publication number
ES2531629T3
ES2531629T3 ES08869976.4T ES08869976T ES2531629T3 ES 2531629 T3 ES2531629 T3 ES 2531629T3 ES 08869976 T ES08869976 T ES 08869976T ES 2531629 T3 ES2531629 T3 ES 2531629T3
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mif
antibody
once
antigen binding
encompasses
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Inventor
Randolf Kerschbaumer
Friedrich Scheiflinger
Manfred Rieger
Michael Thiele
C. Geert Mudde
Juergen Muellberg
Rene Hoet
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Baxter Healthcare SA
Baxter International Inc
Dyax Corp
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Baxter Healthcare SA
Baxter International Inc
Dyax Corp
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
    • C07K16/24—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against cytokines, lymphokines or interferons
    • 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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00—Drugs for disorders of the respiratory system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00—Drugs for disorders of the respiratory system
    • A61P11/06—Antiasthmatics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P13/00—Drugs for disorders of the urinary system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P13/00—Drugs for disorders of the urinary system
    • A61P13/12—Drugs for disorders of the urinary system of the kidneys
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A61P17/06—Antipsoriatics
    • A—HUMAN NECESSITIES
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    • A61P19/00—Drugs for skeletal disorders
    • A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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    • A61P27/00—Drugs for disorders of the senses
    • A61P27/02—Ophthalmic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • A—HUMAN NECESSITIES
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    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/04—Antibacterial agents
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    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P33/00—Antiparasitic agents
    • A61P33/02—Antiprotozoals, e.g. for leishmaniasis, trichomoniasis, toxoplasmosis
    • A61P33/06—Antimalarials
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    • A61P35/00—Antineoplastic agents
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    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A61P35/02—Antineoplastic agents specific for leukemia
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    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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    • A61P37/02—Immunomodulators
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A61P37/08—Antiallergic 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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/14—Vasoprotectives; Antihaemorrhoidals; Drugs for varicose therapy; Capillary stabilisers
    • 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
    • C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
    • C07K2317/52—Constant or Fc region; Isotype
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
    • C07K2317/55—Fab or Fab'
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
    • C07K2317/56—Immunoglobulins specific features characterized by immunoglobulin fragments variable (Fv) region, i.e. VH and/or VL
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
    • C07K2317/56—Immunoglobulins specific features characterized by immunoglobulin fragments variable (Fv) region, i.e. VH and/or VL
    • C07K2317/565—Complementarity determining region [CDR]
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/70—Immunoglobulins specific features characterized by effect upon binding to a cell or to an antigen
    • C07K2317/73—Inducing cell death, e.g. apoptosis, necrosis or inhibition of cell proliferation
    • 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

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  • Heart & Thoracic Surgery (AREA)
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Abstract

Anticuerpo monoclonal o parte de unión a antígeno del mismo que se une específicamente a la región que se abarca los aa 50-68 o la región que abarca los aa 86-102 de MIF humano, e inhibe la función biológica de MIF humano.

Description

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E08869976
27-02-2015
fosfato, dextrosa, glicerol, etanol y similares, así como combinaciones de los mismos. En muchos casos, será preferible incluir agentes isotónicos, por ejemplo, azúcares, polialcoholes tales como manitol, sorbitol, o cloruro de sodio en la composición. Ejemplos adicionales de sustancias farmacéuticamente aceptables son agentes humectantes o cantidades menores de sustancias auxiliares tales como agentes humectantes o emulsionantes, conservantes o tampones, que potencian la vida útil de almacenamiento o eficacia del anticuerpo.
El anticuerpo anti-MIF de la invención y las composiciones farmacéuticas que lo comprenden pueden administrarse en combinación con uno o más de otros agentes terapéuticos, de diagnóstico o profilácticos. Los agentes terapéuticos adicionales incluyen otros agentes antineoplásicos, antitumorales, antiangiogénicos, quimioterápicos o esteroides, dependiendo de la enfermedad que va a tratarse.
Las composiciones farmacéuticas de esta invención pueden estar en una variedad de formas, por ejemplo, formas de dosificación líquidas, semisólidas y sólidas, tales como disoluciones líquidas (por ejemplo, disoluciones inyectables y para infusión), dispersiones o suspensiones, comprimidos, pastillas, polvos, liposomas y supositorios. La forma preferida depende de la aplicación terapéutica y el modo de administración previstos. Composiciones preferidas típicas están en forma de disoluciones inyectables o para infusión, tales como composiciones similares a las usadas para la inmunización pasiva de seres humanos. El modo de administración preferido es parenteral (por ejemplo, intravenoso, subcutáneo, intraperitoneal, intramuscular). En una realización preferida, el anticuerpo se administra mediante infusión o inyección intravenosa. En otra realización preferida, el anticuerpo se administra mediante inyección intramuscular o subcutánea. Tal como apreciará el experto en la técnica, la vía y/o el modo de administración variarán dependiendo de los resultados deseados.
El anticuerpo anti-MIF puede administrarse una vez, pero más preferiblemente se administra múltiples veces. Por ejemplo, el anticuerpo puede administrarse desde tres veces al día hasta una vez cada seis meses o más. La administración puede realizarse en un programa tal como de tres veces al día, dos veces al día, una vez al día, una vez cada dos días, una vez cada tres días, una vez a la semana, una vez cada dos semanas, una vez cada mes, una vez cada dos meses, una vez cada tres meses y una vez cada seis meses.
La invención también abarca el uso de un anticuerpo anti-MIF o un fragmento de unión a antígeno del mismo, en la fabricación de un medicamento para el tratamiento de enfermedades inmunológicas tales como enfermedades inflamatorias y trastornos hiperproliferativos.
La invención abarca además un anticuerpo anti-MIF o un fragmento de unión a antígeno del mismo, para su uso en el tratamiento de enfermedades inmunológicas tales como enfermedades inflamatorias y trastornos hiperproliferativos.
La invención también abarca un anticuerpo anti-MIF o un fragmento de unión a antígeno del mismo, para su uso en métodos de diagnóstico. En una realización, el anticuerpo anti-MIF o parte de unión a antígeno del mismo puede usarse para detectar MIF humano en una muestra biológica.
Los anticuerpos anti-MIF o las partes de unión a antígeno de los mismos también pueden usarse para determinar el nivel de MIF en superficie celular en un tejido o en células derivadas a partir del tejido. En algunas realizaciones, el tejido es tejido enfermo. Entonces puede usarse el tejido en un inmunoensayo para determinar, por ejemplo, niveles de MIF total, niveles de MIF en superficie celular o ubicación de MIF.
La invención se refiere además a kits que comprenden un anticuerpo anti-MIF o una parte de unión a antígeno de la invención o una composición farmacéutica que comprende un anticuerpo o una parte de este tipo. Un kit puede incluir, además del anticuerpo o la composición farmacéutica, agentes de diagnóstico o terapéuticos. Un kit también puede incluir instrucciones para su uso en un método de diagnóstico o terapéutico.
La invención se refiere además a un procedimiento para la identificación de anticuerpos anti-MIF que pueden inhibir la función biológica de MIF humano e inducir un efecto beneficioso en un modelo animal llevando a cabo las siguientes etapas:
a) seleccionar un anticuerpo que se une a MIF activo y no se une a MIF no activo,
b) someter a prueba dicho anticuerpo en ensayos in vitro, tales como ensayo de anulación de glucocorticoides (GCO) o ensayos de proliferación celular,
c) seleccionar un anticuerpo que inhibe GCO y/o la proliferación celular.
Los resultados han mostrado que un anticuerpo anti-MIF que sólo se une a MIF activo y no se une a MIF no activo e inhibe además GCO y/o la proliferación celular induce un efecto beneficioso en un modelo animal (por ejemplo, el ejemplo 6).
La presente invención se ilustrará adicionalmente mediante los siguientes ejemplos, sin ninguna limitación a los
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Claims (1)

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ES08869976.4T 2008-01-04 2008-12-30 Anticuerpos anti-MIF Active ES2531629T3 (es)

Applications Claiming Priority (5)

Application Number Priority Date Filing Date Title
US1898808P 2008-01-04 2008-01-04
US18988P 2008-01-04
US9468508P 2008-09-05 2008-09-05
US94685P 2008-09-05
PCT/EP2008/011146 WO2009086920A1 (en) 2008-01-04 2008-12-30 Anti mif antibodies

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ES2531629T3 true ES2531629T3 (es) 2015-03-18

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ES16183733T Active ES2791333T3 (es) 2008-01-04 2008-12-30 Anticuerpos anti-MIF para su uso en el tratamiento de enfermedades inflamatorias
ES14163839.5T Active ES2623653T3 (es) 2008-01-04 2008-12-30 Anticuerpos anti-MIF
ES08869976.4T Active ES2531629T3 (es) 2008-01-04 2008-12-30 Anticuerpos anti-MIF

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ES16183733T Active ES2791333T3 (es) 2008-01-04 2008-12-30 Anticuerpos anti-MIF para su uso en el tratamiento de enfermedades inflamatorias
ES14163839.5T Active ES2623653T3 (es) 2008-01-04 2008-12-30 Anticuerpos anti-MIF

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US (3) US20090220521A1 (es)
EP (4) EP3118223B8 (es)
JP (1) JP5502752B2 (es)
KR (2) KR101654678B1 (es)
CN (2) CN103724430B (es)
AU (1) AU2008346517B2 (es)
BR (1) BRPI0821682A2 (es)
CA (1) CA2711029A1 (es)
CY (1) CY1117302T1 (es)
DK (1) DK2231707T3 (es)
ES (3) ES2791333T3 (es)
HK (1) HK1147762A1 (es)
HR (1) HRP20150224T1 (es)
IL (1) IL206715A (es)
MX (1) MX2010007406A (es)
NZ (3) NZ586600A (es)
PL (2) PL2231707T3 (es)
PT (1) PT2231707E (es)
RS (1) RS53906B1 (es)
RU (2) RU2509777C2 (es)
SI (1) SI2231707T1 (es)
WO (1) WO2009086920A1 (es)
ZA (1) ZA201004973B (es)

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DK2231707T3 (en) * 2008-01-04 2015-03-02 Baxter Int Anti-mif antibodies
WO2013010955A1 (en) 2011-07-15 2013-01-24 Morphosys Ag Antibodies that are cross-reactive for macrophage migration inhibitory factor (mif) and d-dopachrome tautomerase (d-dt)
WO2013050457A1 (en) 2011-10-07 2013-04-11 Baxter Healthcare S.A. Characterization of cho-mif gene and protein, and use thereof
WO2013050453A1 (en) 2011-10-07 2013-04-11 Baxter Healthcare S.A. Oxmif as a diagnostic marker
AU2013203957B9 (en) * 2012-04-16 2015-10-15 Baxalta GmbH Combination Therapy of Anti-MIF Antibodies and Glucocorticoids
AU2013202693B2 (en) * 2012-04-16 2015-01-22 Baxalta GmbH Combination Therapy of Anti-MIF Antibodies and Chemotherapeutics
JP2015523572A (ja) * 2012-07-10 2015-08-13 バクスター・ヘルスケヤー・ソシエテ・アノニムＢａｘｔｅｒ Ｈｅａｌｔｈｃａｒｅ ＳＡ 抗ｍｉｆ免疫組織化学法
SG11201504392XA (en) * 2012-12-07 2015-07-30 Baxter Int Anti-mif antibody cell migration assay
AU2015206178A1 (en) * 2014-01-03 2016-07-07 Baxalta GmbH Anti-MIF immunohistochemistry
US10626166B2 (en) 2014-08-22 2020-04-21 Baxalta Incorporated Detection of CHO-MIF contaminations
EP3277718B1 (en) 2015-03-31 2021-03-24 Baxalta GmbH Dosage regimen for anti-mif antibodies
WO2016184886A1 (en) 2015-05-18 2016-11-24 Baxalta GmbH Anti-mif antibodies in the treatment of cancers containing mutant tp53 and/or mutant ras
WO2018050833A1 (en) * 2016-09-15 2018-03-22 Ablynx Nv Immunoglobulin single variable domains directed against macrophage migration inhibitory factor
CN109868311B (zh) * 2017-12-01 2023-10-20 上海市精神卫生中心 Mif及其预测二代抗精神病药物诱导的代谢不良反应的应用
JP2021526820A (ja) * 2018-06-07 2021-10-11 オンコワン・リサーチ・アンド・ディベロップメント・ゲゼルシャフト・ミト・ベシュレンクテル・ハフツング 癌治療のための抗ｏｘＭＩＦ／抗ＣＤ３抗体
EP3757252B1 (en) 2019-06-28 2022-03-30 Walter Ag A coated cutting tool
AU2020397229A1 (en) 2019-12-06 2022-06-30 Oncoone Research & Development Gmbh Anti-oxMIF/anti-CD3 bispecific antibody constructs
WO2022069712A1 (en) * 2020-10-02 2022-04-07 Oncoone Research & Development Gmbh IMPROVED ANTI-oxMIF ANTIBODIES WITH REDUCED AGGREGATION POTENTIAL AND REDUCED HYDROPHOBICITY
WO2022167474A1 (en) 2021-02-03 2022-08-11 Oncoone Research & Development Gmbh ANTI-oxMIF RADIOIMMUNOCONJUGATE
CA3230723A1 (en) 2021-09-03 2023-03-09 Oncoone Research & Development Gmbh Improved fc silenced anti-oxmif antibodies with reduced aggregation potential and reduced hydrophobicity
WO2023133361A2 (en) * 2022-01-10 2023-07-13 Phenomic Ai Anti-cthrc1 fusion proteins and methods of using the same
CN114573693A (zh) * 2022-04-25 2022-06-03 中国人民解放军陆军军医大学 一种听觉发育中免疫调节分子mif抗体制备方法
CN115814069B (zh) * 2022-10-31 2023-07-21 四川大学华西医院 Mif基因敲除的肿瘤细胞在制备肿瘤疫苗中的用途

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