WO1991007418A1 - Chimeric mouse-human a10 antibody with specificity to a human tumor cell antigen - Google Patents

Chimeric mouse-human a10 antibody with specificity to a human tumor cell antigen Download PDF

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Publication number
WO1991007418A1
WO1991007418A1 PCT/US1990/006620 US9006620W WO9107418A1 WO 1991007418 A1 WO1991007418 A1 WO 1991007418A1 US 9006620 W US9006620 W US 9006620W WO 9107418 A1 WO9107418 A1 WO 9107418A1
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WIPO (PCT)
Prior art keywords
antibody
alo
fragment
chain
derivative
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Application number
PCT/US1990/006620
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English (en)
French (fr)
Inventor
Marc D. Better
Arnold H. Horwitz
Shau-Ping Lei
Randy R. Robinson
Original Assignee
Xoma Corporation
Green Cross Corporation
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 Xoma Corporation, Green Cross Corporation filed Critical Xoma Corporation
Publication of WO1991007418A1 publication Critical patent/WO1991007418A1/en

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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00Medicinal preparations containing antigens or antibodies
    • A61K39/395Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K49/00Preparations for testing in vivo
    • A61K49/0004Screening or testing of compounds for diagnosis of disorders, assessment of conditions, e.g. renal clearance, gastric emptying, testing for diabetes, allergy, rheuma, pancreas functions
    • A61K49/0008Screening agents using (non-human) animal models or transgenic animal models or chimeric hosts, e.g. Alzheimer disease animal model, transgenic model for heart failure
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/50Medicinal 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
    • A61K47/51Medicinal 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
    • A61K47/68Medicinal 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
    • A61K47/6835Medicinal 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
    • A61K47/6851Medicinal 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
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K51/00Preparations containing radioactive substances for use in therapy or testing in vivo
    • A61K51/02Preparations containing radioactive substances for use in therapy or testing in vivo characterised by the carrier, i.e. characterised by the agent or material covalently linked or complexing the radioactive nucleus
    • A61K51/04Organic compounds
    • A61K51/08Peptides, e.g. proteins, carriers being peptides, polyamino acids, proteins
    • A61K51/10Antibodies or immunoglobulins; Fragments thereof, the carrier being an antibody, an immunoglobulin or a fragment thereof, e.g. a camelised human single domain antibody or the Fc fragment of an antibody
    • A61K51/1084Antibodies or immunoglobulins; Fragments thereof, the carrier being an antibody, an immunoglobulin or a fragment thereof, e.g. a camelised human single domain antibody or the Fc fragment of an antibody the antibody being a hybrid immunoglobulin
    • A61K51/1087Antibodies or immunoglobulins; Fragments thereof, the carrier being an antibody, an immunoglobulin or a fragment thereof, e.g. a camelised human single domain antibody or the Fc fragment of an antibody the antibody being a hybrid immunoglobulin the immunoglobulin comprises domains from different animal species, e.g. chimeric immunoglobulins
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K16/00Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • C07K16/18Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
    • C07K16/28Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
    • C07K16/30Immunoglobulins [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
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K16/00Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • C07K16/46Hybrid immunoglobulins
    • C07K16/461Igs containing Ig-regions, -domains or -residues form different species
    • C07K16/462Igs containing a variable region (Fv) from one specie and a constant region (Fc) from another
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2123/00Preparations for testing in vivo
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00Medicinal preparations containing peptides
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K2317/00Immunoglobulins specific features
    • C07K2317/20Immunoglobulins specific features characterized by taxonomic origin
    • C07K2317/24Immunoglobulins specific features characterized by taxonomic origin containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K2319/00Fusion polypeptide
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K2319/00Fusion polypeptide
    • C07K2319/01Fusion polypeptide containing a localisation/targetting motif
    • C07K2319/034Fusion polypeptide containing a localisation/targetting motif containing a motif for targeting to the periplasmic space of Gram negative bacteria as a soluble protein, i.e. signal sequence should be cleaved

Definitions

  • Plasmid pING1712 contains the following gene regulatory elements useful for expression in mammalian cells: 1) the IgH enhancer element, 2) the Abelson LTR promoter, 3) the SV40 16S splice site, and 4) a human K polyadenylation signal sequence. It also contains the entire human C ⁇ region (Liu, A.Y., et al. supra) and the GPJ gene which allows for ycophenolic acid resistance in transfected cells.
  • the immune spleen cells and the mouse myeloma, P3U1 (Curr. Top. Microbiol. Immunol.. 81 . :1, 1979), were mixed in the ratio of about 2:1 (2.2 X 10 7 : 1.6 X 10 7 ) and a fusion reaction was carried out for 2 min. using 45% polyethylene glycol (average molecular weight: 4000) by a partial modification of the method of Kohler et al . (Immunological Methods. Academic Press, New York, p. 391, 1979). The treated cells were centrifuged, and the supernatant was discarded. The cells were then incubated for five minutes in HAT medium (see below) and inoculated into 96-well flat bottom microplates (0.1 ml per well) and cultured in 7.5% CO .
  • Dulbecco's modified Eagle medium (DMEM) was obtained from Nissui Seiyaku Co.
  • the polyadenylation/transcription termination region of the K expression vector was also modified.
  • the first step was the Hindlll digestion and religation of plasmid pING2121a, which is identical to pING2108a (Liu, A.Y. et al.. supra) except that the L6 VL was used in its construction instead of the 2H7 VL, to form pING2121a-deltaH.
  • the l.lkb Bglll to BamHI fragment of mouse genomic DNA distal to the polyadenylation site (Xu, M. et al.. J. Biol. Chem. 261: 3838 (1986) was isolated from pS107A (provided by Dr.
  • the H chain enhancer was deleted from pING1711 by EcoRI digestion, T4 polymerase treatment, ligation to Aatll oligonucleotide linker, and cleavage and religation with Aatll to form the 7.7kb expression vector pING1714.
  • the J-region mutagenesis primer 5'-GTTTTATTTCAAGCTTGGTCC-3' was used to insert a Hindlll site into the M13 subclone pTK2 to generate pTK4, and the oligonucleotide 5'-GAACTTTGGTCGACAGCAACGGG-3' was used to insert a Sail restriction site into pTK4 upstream of the initiation codon ATG to generate pTK5.
  • the restriction fragment containing the AlO VL region bounded by Sail and Hindlll was then cloned into the expression vector pING1712 to generate the final chimeric AlO L chain expression vector, pING2252.
  • the approxi ⁇ mately 340 bp fragment containing the Fd V-region was purified and ligated to pING1500 that was cut with Sstl, treated with T4 polymerase, and cut with Xhol, Figure 5E, along with the BstEII (partial digest) to Xhol restriction fragment containing the human Fd C region and 3 nucleotides following the termination codon from pF3D, Figure 5F, (the human C ⁇ l region in pF3D was previously generated by introducing a stop codon in hinge, Robinson, R.R. et al . , supra) .
  • the resulting plasmid that contained a pelB::A10 Fd fusion was sequenced to determine that the proper in-frame fusion was formed. This plasmid was called pTK13.

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Immunology (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Veterinary Medicine (AREA)
  • Organic Chemistry (AREA)
  • Epidemiology (AREA)
  • Animal Behavior & Ethology (AREA)
  • Public Health (AREA)
  • Engineering & Computer Science (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Zoology (AREA)
  • Biophysics (AREA)
  • Molecular Biology (AREA)
  • Cell Biology (AREA)
  • Genetics & Genomics (AREA)
  • Biochemistry (AREA)
  • Microbiology (AREA)
  • Mycology (AREA)
  • Optics & Photonics (AREA)
  • Physics & Mathematics (AREA)
  • Biomedical Technology (AREA)
  • Diabetes (AREA)
  • Endocrinology (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Pathology (AREA)
  • Rheumatology (AREA)
  • Toxicology (AREA)
  • Urology & Nephrology (AREA)
  • Preparation Of Compounds By Using Micro-Organisms (AREA)
  • Peptides Or Proteins (AREA)
  • Micro-Organisms Or Cultivation Processes Thereof (AREA)
  • Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
PCT/US1990/006620 1989-11-13 1990-11-13 Chimeric mouse-human a10 antibody with specificity to a human tumor cell antigen WO1991007418A1 (en)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US43501289A 1989-11-13 1989-11-13
US435,012 1989-11-13

Publications (1)

Publication Number Publication Date
WO1991007418A1 true WO1991007418A1 (en) 1991-05-30

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Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US1990/006620 WO1991007418A1 (en) 1989-11-13 1990-11-13 Chimeric mouse-human a10 antibody with specificity to a human tumor cell antigen

Country Status (6)

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EP (1) EP0457875A4 (ko)
JP (1) JPH03206886A (ko)
KR (1) KR910009284A (ko)
AU (1) AU634314B2 (ko)
CA (1) CA2044590A1 (ko)
WO (1) WO1991007418A1 (ko)

Cited By (28)

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Publication number Priority date Publication date Assignee Title
US5641751A (en) * 1995-05-01 1997-06-24 Centocor, Inc. Tumor necrosis factor inhibitors
WO1997037690A2 (en) * 1996-04-10 1997-10-16 Sangstat Medical Corporation Cytomodulating conjugates of members of specific binding pairs
WO1998034645A1 (en) * 1997-02-05 1998-08-13 Angelini Ricerche S.P.A. Societa' Consortile A composition for administration by the intranasal, sublingual or vaginal route
US6645493B1 (en) * 1993-05-17 2003-11-11 The Picower Institute For Medical Research Composition containing anti-MIF antibody
US7033594B2 (en) 2000-03-31 2006-04-25 Purdue Research Foundation Method of treatment using ligand-immunogen conjugates
EP2060272A2 (en) 2002-05-15 2009-05-20 Endocyte, Inc. Vitamin-mitomycin conjugates
US7696324B2 (en) 1998-11-30 2010-04-13 Perlan Therapeutics, Inc. Humanized antibodies
EP2374480A2 (en) 2005-08-19 2011-10-12 Endocyte, Inc. Mutli-drug ligand conjugates
EP2382995A2 (en) 2005-08-19 2011-11-02 Endocyte, Inc. Ligand conjugates of Vinca alkaloids, analogs and derivatives
US8168164B2 (en) 2006-02-03 2012-05-01 Purdue Research Foundation Targeted conjugates and radiation
EP2481427A1 (en) 2007-03-14 2012-08-01 Endocyte, Inc. Folate-Tubulysin conjugates
EP2517729A2 (en) 2003-01-27 2012-10-31 Endocyte, Inc. Vitamin receptor binding drug delivery conjugates
US8394771B1 (en) 2001-07-19 2013-03-12 Perlan Therapeutics, Inc. Multimeric proteins and methods of making and using same
US8907058B2 (en) 2007-08-17 2014-12-09 Purdue Research Foundation PSMA binding ligand-linker conjugates and methods for using
US9090563B2 (en) 2004-07-23 2015-07-28 Endocyte, Inc. Bivalent linkers and conjugates thereof
US9138484B2 (en) 2007-06-25 2015-09-22 Endocyte, Inc. Conjugates containing hydrophilic spacer linkers
US9187521B2 (en) 2007-10-25 2015-11-17 Endocyte, Inc. Tubulysins and processes for preparing
US9505747B2 (en) 2012-03-29 2016-11-29 Endocyte, Inc. Processes for preparing tubulysin derivatives and conjugates thereof
US9636413B2 (en) 2012-11-15 2017-05-02 Endocyte, Inc. Conjugates for treating diseases caused by PSMA expressing cells
US9662402B2 (en) 2012-10-16 2017-05-30 Endocyte, Inc. Drug delivery conjugates containing unnatural amino acids and methods for using
US9877965B2 (en) 2007-06-25 2018-01-30 Endocyte, Inc. Vitamin receptor drug delivery conjugates for treating inflammation
US9951324B2 (en) 2010-02-25 2018-04-24 Purdue Research Foundation PSMA binding ligand-linker conjugates and methods for using
US9958456B2 (en) 2011-10-07 2018-05-01 Baxalta Incorporated OxMIF as a diagnostic marker
US10080805B2 (en) 2012-02-24 2018-09-25 Purdue Research Foundation Cholecystokinin B receptor targeting for imaging and therapy
US10398791B2 (en) 2013-10-18 2019-09-03 Deutsches Krebsforschungszentrum Labeled inhibitors of prostate specific membrane antigen (PSMA), their use as imaging agents and pharmaceutical agents for the treatment of prostate cancer
US10624972B2 (en) 2015-03-13 2020-04-21 Endocyte, Inc. Conjugates for treating diseases
US10898596B2 (en) 2015-01-07 2021-01-26 Endocyte, Inc. Conjugates for imaging
WO2022219569A1 (en) 2021-04-16 2022-10-20 Novartis Ag Folate receptor-targeted radiotherapeutic agents and their use

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AU625613B2 (en) * 1988-01-05 1992-07-16 Novartis Ag Novel chimeric antibodies
GB8800078D0 (en) * 1988-01-05 1988-02-10 Ciba Geigy Ag Novel antibodies
IL89489A0 (en) * 1988-03-09 1989-09-10 Hybritech Inc Chimeric antibodies directed against human carcinoembryonic antigen

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Proceedings of The National Academy of Science, Volume 82, issued February 1985, A.N. HOUGHTON, et al., "Mouse monoclonal IgG3 antibody detecting GD3 ganglioside: A phase I trial in patients with malignant melanoma, pages 1242-1246. *
Proceedings of the National Academy of Science, Volume 84, issued May 1987, A.Y. LIU, et al., "Chimeric mouse-human IgG1 antibody that can mediate lysis of cancer cells", pages 3439-3443, see Abstract and pages 3439-40. *
See also references of EP0457875A4 *
The Journal of Biological Chemistry, Volume 261 No. 8, issued 15 March 1986, XU, et al., "Transcription Termination and Chromatin Structure of the Active Immunoglobulin k Gene Locus", pages 3838-3845. *
The Journal of Immunology, Volume 139, No. 10 issued 15 November 1987, A.Y. LIU, et al., "Production of a Mouse-Human Chimeric Monoclonal Antibody To CD20 With Potent Fc-Dependent Biologic Activity", pages 3521-3526. See Abstract. *

Cited By (69)

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US7517523B2 (en) 1993-05-17 2009-04-14 Cytokine Pharmasciences, Inc. Anti-MIF antibodies
US6645493B1 (en) * 1993-05-17 2003-11-11 The Picower Institute For Medical Research Composition containing anti-MIF antibody
US5641751A (en) * 1995-05-01 1997-06-24 Centocor, Inc. Tumor necrosis factor inhibitors
WO1997037690A2 (en) * 1996-04-10 1997-10-16 Sangstat Medical Corporation Cytomodulating conjugates of members of specific binding pairs
WO1997037690A3 (en) * 1996-04-10 1998-03-05 Sangstat Medical Corp Cytomodulating conjugates of members of specific binding pairs
WO1998034645A1 (en) * 1997-02-05 1998-08-13 Angelini Ricerche S.P.A. Societa' Consortile A composition for administration by the intranasal, sublingual or vaginal route
US7696324B2 (en) 1998-11-30 2010-04-13 Perlan Therapeutics, Inc. Humanized antibodies
US8586712B2 (en) 1998-11-30 2013-11-19 Perlan Therapeutics, Inc. Humanized antibodies
US7033594B2 (en) 2000-03-31 2006-04-25 Purdue Research Foundation Method of treatment using ligand-immunogen conjugates
US8105608B2 (en) 2000-03-31 2012-01-31 Purdue Research Foundation Method of treatment using ligand-immunogen conjugates
US8394771B1 (en) 2001-07-19 2013-03-12 Perlan Therapeutics, Inc. Multimeric proteins and methods of making and using same
EP2060272A2 (en) 2002-05-15 2009-05-20 Endocyte, Inc. Vitamin-mitomycin conjugates
US7910594B2 (en) 2002-05-15 2011-03-22 Endocyte, Inc. Vitamin-mitomycin conjugates
EP2517729A2 (en) 2003-01-27 2012-10-31 Endocyte, Inc. Vitamin receptor binding drug delivery conjugates
EP2529758A2 (en) 2003-01-27 2012-12-05 Endocyte, Inc. Vitamin receptor binding drug delivery conjugates
EP2517730A2 (en) 2003-01-27 2012-10-31 Endocyte, Inc. Vitamin receptor binding drug delivery conjugates
US10647676B2 (en) 2004-07-23 2020-05-12 Endocyte, Inc. Bivalent linkers and conjugates thereof
US9090563B2 (en) 2004-07-23 2015-07-28 Endocyte, Inc. Bivalent linkers and conjugates thereof
US9550734B2 (en) 2004-07-23 2017-01-24 Endocyte, Inc. Bivalent linkers and conjugates thereof
EP2382995A2 (en) 2005-08-19 2011-11-02 Endocyte, Inc. Ligand conjugates of Vinca alkaloids, analogs and derivatives
EP2374480A2 (en) 2005-08-19 2011-10-12 Endocyte, Inc. Mutli-drug ligand conjugates
US8168164B2 (en) 2006-02-03 2012-05-01 Purdue Research Foundation Targeted conjugates and radiation
EP2481427A1 (en) 2007-03-14 2012-08-01 Endocyte, Inc. Folate-Tubulysin conjugates
EP2489372A2 (en) 2007-03-14 2012-08-22 Endocyte, Inc. Binding ligand linked drug delivery conjugates of tubulysins
US9555139B2 (en) 2007-03-14 2017-01-31 Endocyte, Inc. Binding ligand linked drug delivery conjugates of tubulysins
US9138484B2 (en) 2007-06-25 2015-09-22 Endocyte, Inc. Conjugates containing hydrophilic spacer linkers
US10738086B2 (en) 2007-06-25 2020-08-11 Endocyte Inc. Conjugates containing hydrophilic spacer linkers
US10500204B2 (en) 2007-06-25 2019-12-10 Endocyte, Inc. Vitamin receptor drug delivery conjugates for treating inflammation
US9877965B2 (en) 2007-06-25 2018-01-30 Endocyte, Inc. Vitamin receptor drug delivery conjugates for treating inflammation
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US8907058B2 (en) 2007-08-17 2014-12-09 Purdue Research Foundation PSMA binding ligand-linker conjugates and methods for using
US10046054B2 (en) 2007-08-17 2018-08-14 Purdue Research Foundation PSMA binding ligand-linker conjugates and methods for using
US9193763B2 (en) 2007-08-17 2015-11-24 Purdue Research Foundation PSMA binding ligand-linker conjugates and methods for using
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US10406240B2 (en) 2007-08-17 2019-09-10 Purdue Research Foundation PSMA binding ligand-linker conjugates and methods for using
US11369590B2 (en) 2007-08-17 2022-06-28 Purdue Research Foundation PSMA binding ligand-linker conjugates and methods for using
US10624970B2 (en) 2007-08-17 2020-04-21 Purdue Research Foundation PSMA binding ligand-linker conjugates and methods for using
US10485878B2 (en) 2007-08-17 2019-11-26 Purdue Research Foundation PSMA binding ligand-linker conjugates and methods for using
US10624971B2 (en) 2007-08-17 2020-04-21 Purdue Research Foundation PSMA binding ligand-linker conjugates and methods for using
US10517956B2 (en) 2007-08-17 2019-12-31 Purdue Research Foundation PSMA binding ligand-linker conjugates and methods for using
US11298341B2 (en) 2007-08-17 2022-04-12 Purdue Research Foundation PSMA binding ligand-linker conjugates and methods for using
US10624969B2 (en) 2007-08-17 2020-04-21 Purdue Research Foundation PSMA binding ligand-linker conjugates and methods for using
US9187521B2 (en) 2007-10-25 2015-11-17 Endocyte, Inc. Tubulysins and processes for preparing
US9745341B2 (en) 2007-10-25 2017-08-29 Endocyte, Inc. Tubulysins and processes for preparing
US11155800B2 (en) 2010-02-25 2021-10-26 Purdue Research Foundation PSMA binding ligand-linker conjugates and methods for using
US9951324B2 (en) 2010-02-25 2018-04-24 Purdue Research Foundation PSMA binding ligand-linker conjugates and methods for using
US10557128B2 (en) 2010-02-25 2020-02-11 Purdue Research Foundation PSMA binding ligand-linker conjugates and methods for using
US9958456B2 (en) 2011-10-07 2018-05-01 Baxalta Incorporated OxMIF as a diagnostic marker
US10080805B2 (en) 2012-02-24 2018-09-25 Purdue Research Foundation Cholecystokinin B receptor targeting for imaging and therapy
US10765756B2 (en) 2012-02-24 2020-09-08 Purdue Research Foundation Cholecystokinin B receptor targeting for imaging and therapy
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US9505747B2 (en) 2012-03-29 2016-11-29 Endocyte, Inc. Processes for preparing tubulysin derivatives and conjugates thereof
US9662402B2 (en) 2012-10-16 2017-05-30 Endocyte, Inc. Drug delivery conjugates containing unnatural amino acids and methods for using
US9636413B2 (en) 2012-11-15 2017-05-02 Endocyte, Inc. Conjugates for treating diseases caused by PSMA expressing cells
US10912840B2 (en) 2012-11-15 2021-02-09 Endocyte, Inc. Conjugates for treating diseases caused by PSMA expressing cells
US9782493B2 (en) 2012-11-15 2017-10-10 Endocyte, Inc. Conjugates for treating diseases caused by PSMA expressing cells
US10471160B2 (en) 2013-10-18 2019-11-12 Deutsches Krebsforschungszentrum Labeled inhibitors of prostate specific membrane antigen (PSMA), their use as imaging agents and pharmaceutical agents for the treatment of prostate cancer
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US10398791B2 (en) 2013-10-18 2019-09-03 Deutsches Krebsforschungszentrum Labeled inhibitors of prostate specific membrane antigen (PSMA), their use as imaging agents and pharmaceutical agents for the treatment of prostate cancer
US11931430B2 (en) 2013-10-18 2024-03-19 Novartis Ag Labeled inhibitors of prostate specific membrane antigen (PSMA) as agents for the treatment of prostate cancer
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US10898596B2 (en) 2015-01-07 2021-01-26 Endocyte, Inc. Conjugates for imaging
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WO2022219569A1 (en) 2021-04-16 2022-10-20 Novartis Ag Folate receptor-targeted radiotherapeutic agents and their use

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KR910009284A (ko) 1991-06-28
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JPH03206886A (ja) 1991-09-10
CA2044590A1 (en) 1991-05-14

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