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  1. Article ; Online: Enhancing Selectivity of Protein Biopharmaceuticals in Ion Exchange Chromatography through Addition of Organic Modifiers.

    Duivelshof, Bastiaan Laurens / Bouvarel, Thomas / Pirner, Sebastian / Larraillet, Vincent / Knaupp, Alexander / Koll, Hans / D'Atri, Valentina / Guillarme, Davy

    International journal of molecular sciences

    2023  Volume 24, Issue 23

    Abstract: Charge heterogeneity among therapeutic monoclonal antibodies (mAbs) is considered an important critical quality attribute and requires careful characterization to ensure safe and efficacious drug products. The charge heterogeneity among mAbs is the ... ...

    Abstract Charge heterogeneity among therapeutic monoclonal antibodies (mAbs) is considered an important critical quality attribute and requires careful characterization to ensure safe and efficacious drug products. The charge heterogeneity among mAbs is the result of chemical and enzymatic post-translational modifications and leads to the formation of acidic and basic variants that can be characterized using cation exchange chromatography (CEX). Recently, the use of mass spectrometry-compatible salt-mediated pH gradients has gained increased attention to elute the proteins from the charged stationary phase material. However, with the increasing antibody product complexity, more and more selectivity is required. Therefore, in this study, we set out to improve the selectivity by using a solvent-enriched mobile phase composition for the analysis of a variety of mAbs and bispecific antibody products. It was found that the addition of the solvents to the mobile phase appeared to modify the hydrate shell surrounding the protein and alter the retention behavior of the studied proteins. Therefore, this work demonstrates that the use of solvent-enriched mobile phase composition could be an attractive additional method parameter during method development in CEX.
    MeSH term(s) Hydrogen-Ion Concentration ; Biological Products ; Antibodies, Monoclonal/chemistry ; Solvents ; Indicators and Reagents ; Chromatography, Ion Exchange/methods
    Chemical Substances Biological Products ; Antibodies, Monoclonal ; Solvents ; Indicators and Reagents
    Language English
    Publishing date 2023-11-22
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2019364-6
    ISSN 1422-0067 ; 1422-0067 ; 1661-6596
    ISSN (online) 1422-0067
    ISSN 1422-0067 ; 1661-6596
    DOI 10.3390/ijms242316623
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Detection of a phosphorylated glycine-serine linker in an IgG-based fusion protein.

    Tyshchuk, Oksana / Völger, Hans Rainer / Ferrara, Claudia / Bulau, Patrick / Koll, Hans / Mølhøj, Michael

    mAbs

    2017  Volume 9, Issue 1, Page(s) 94–103

    Abstract: Molecular mass determination by electrospray ionization mass spectrometry of a recombinant IgG-based fusion protein (mAb1-F) produced in human embryonic kidney (HEK) cells demonstrated the presence of a dominant +79 Da product variant. Using LC-MS ... ...

    Abstract Molecular mass determination by electrospray ionization mass spectrometry of a recombinant IgG-based fusion protein (mAb1-F) produced in human embryonic kidney (HEK) cells demonstrated the presence of a dominant +79 Da product variant. Using LC-MS tryptic peptide mapping analysis and collision-induced dissociation (CID) and electron-transfer/higher-energy collision dissociation fragmentations, the modification was localized to the C-terminal serine residue of a glycine-serine linker [(G
    Language English
    Publishing date 2017-01
    Publishing country United States
    Document type Journal Article
    ISSN 1942-0870
    ISSN (online) 1942-0870
    DOI 10.1080/19420862.2016.1236165
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article: Zur Handhabung und Übertragung Tiefgefrorener Rinderembryonen

    Koll, Hans

    veterinär spiegel

    2003  Volume 13, Issue 02, Page(s) 119–123

    Language German
    Publishing date 2003-02-01
    Publisher Georg Thieme Verlag, Stuttgart
    Publishing place Stuttgart ; New York
    Document type Article
    ISSN 1868-0437 ; 0940-8711
    ISSN (online) 1868-0437
    ISSN 0940-8711
    DOI 10.1055/s-0029-1239413
    Database Thieme publisher's database

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  4. Article ; Online: Developability assessment during the selection of novel therapeutic antibodies.

    Jarasch, Alexander / Koll, Hans / Regula, Joerg T / Bader, Martin / Papadimitriou, Apollon / Kettenberger, Hubert

    Journal of pharmaceutical sciences

    2015  Volume 104, Issue 6, Page(s) 1885–1898

    Abstract: Therapeutic antibodies and antibody derivatives comprise the majority of today's biotherapeutics. Routine methods to generate novel antibodies, such as immunization and phage-display, often give rise to several candidates with desired functional ... ...

    Abstract Therapeutic antibodies and antibody derivatives comprise the majority of today's biotherapeutics. Routine methods to generate novel antibodies, such as immunization and phage-display, often give rise to several candidates with desired functional properties. On the contrary, resource-intense steps such as the development of a cell line, a manufacturing process, or a formulation, are typically carried out for only one candidate. Therefore, "developability," that is, the likelihood for the successful development of a lead candidate into a stable, manufacturable, safe, and efficacious drug, may be used as an additional selection criterion. Employing a set of small-scale, fast, and predictive tests addressing biochemical and biophysical features, as well as in vivo fate can help to identify a clinical candidate molecule with promising properties at an early stage of drug development. This article gives an overview of existing methods for developability testing and shows how these assays can be interlaced in the lead selection process.
    MeSH term(s) Animals ; Antibodies, Monoclonal/chemistry ; Antibodies, Monoclonal/immunology ; Antibodies, Monoclonal/pharmacology ; Drug Discovery/methods ; Glycosylation ; Humans ; Models, Molecular ; Protein Conformation ; Protein Stability
    Chemical Substances Antibodies, Monoclonal
    Language English
    Publishing date 2015-06
    Publishing country United States
    Document type Journal Article ; Review
    ZDB-ID 3151-3
    ISSN 1520-6017 ; 0022-3549
    ISSN (online) 1520-6017
    ISSN 0022-3549
    DOI 10.1002/jps.24430
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    Uf I Zs.50: Show issues Location:
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  5. Book ; Thesis: Laparoskopie in der Regio epigastrica des Rindes

    Koll, Hans

    1995  

    Author's details von Hans Koll
    Language German
    Size 1 Mikrofiche, 24x
    Edition [Mikrofilm-Ausg., Printing Master]
    Document type Book ; Thesis
    Thesis / German Habilitation thesis @Hannover, Tierärztl. Hochsch., Diss., 1930
    Database Special collection on veterinary medicine and general parasitology

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  6. Article ; Online: Determination of antibody glycosylation by mass spectrometry.

    Jäger, Christiane / Ferrara, Claudia / Umaña, Pablo / Zeck, Anne / Regula, Jörg Thomas / Koll, Hans

    Methods in molecular biology (Clifton, N.J.)

    2012  Volume 901, Page(s) 195–208

    Abstract: Immunoglobulin (Ig) G is formed by two antigen-binding moieties termed Fabs and a conserved Fc -portion, which interacts with components of the immune systems. Within the Fc, N-linked carbohydrates are attached to each conserved asparagine residue at ... ...

    Abstract Immunoglobulin (Ig) G is formed by two antigen-binding moieties termed Fabs and a conserved Fc -portion, which interacts with components of the immune systems. Within the Fc, N-linked carbohydrates are attached to each conserved asparagine residue at position 297 within the CH2 domain. These oligosaccharide moieties introduce a higher degree of heterogeneity within the molecule, by influencing stability of the antibody and its mediated effector functions, such as antibody-dependent cellular cytotoxicity and complement-dependent cytotoxicity (CDC). The carbohydrate moieties can vary strongly depending on the production host and can be manipulated by different fermentation conditions, thereby influencing the function of the antibody. Therefore it is necessary to carefully monitor changes in the carbohydrate composition during cell line development and production processes. This chapter describes two different mass spectrometry based methods used for analyses of the carbohydrate moieties attached to the Fc-part of human IgG1. In the first approach, the glycans are released from the antibody by endoglycosidase (Peptide N Glycosidase F) digestion and monitored by matrix-assisted laser desorption ionization-time-of-flight mass spectrometry (MS), whereas in the second method the carbohydrate structures, still attached to an enzymatically produced Fc-fragment, are analyzed by electrospray ionization mass spectrometry.
    MeSH term(s) Animals ; Antibodies/metabolism ; Glycosylation ; Humans ; Mass Spectrometry/methods ; Spectrometry, Mass, Electrospray Ionization ; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
    Chemical Substances Antibodies
    Language English
    Publishing date 2012
    Publishing country United States
    Document type Journal Article
    ISSN 1940-6029
    ISSN (online) 1940-6029
    DOI 10.1007/978-1-61779-931-0_13
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Book ; Thesis: Untersuchungen zum Mechanismus der konservativen intramitochondrialen Sortierung von Proteinen des Intermembranraums

    Koll, Hans

    1991  

    Author's details von Hans Koll
    Language Undetermined
    Size VI, 163 S, graph. Darst, 21 cm
    Document type Book ; Thesis
    Thesis / German Habilitation thesis @München, Univ., Diss. : 1992
    Database Former special subject collection: coastal and deep sea fishing

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  8. Book ; Thesis: Untersuchungen zum Mechanismus der konservativen intramitochondrialen Sortierung von Proteinen des Intermembranraums

    Koll, Hans

    1991  

    Author's details von Hans Koll
    Language Undetermined
    Size VI, 163 S, graph. Darst, 21 cm
    Document type Book ; Thesis
    Thesis / German Habilitation thesis @München, Univ., Diss. : 1992
    Database Library catalogue of the German National Library of Science and Technology (TIB), Hannover

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  9. Article ; Online: CD25-T

    Solomon, Isabelle / Amann, Maria / Goubier, Anne / Arce Vargas, Frederick / Zervas, Dimitrios / Qing, Chen / Henry, Jake Y / Ghorani, Ehsan / Akarca, Ayse U / Marafioti, Teresa / Śledzińska, Anna / Werner Sunderland, Mariana / Franz Demane, Dafne / Clancy, Joanne Ruth / Georgiou, Andrew / Salimu, Josephine / Merchiers, Pascal / Brown, Mark Adrian / Flury, Reto /
    Eckmann, Jan / Murgia, Claudio / Sam, Johannes / Jacobsen, Bjoern / Marrer-Berger, Estelle / Boetsch, Christophe / Belli, Sara / Leibrock, Lea / Benz, Joerg / Koll, Hans / Sutmuller, Roger / Peggs, Karl S / Quezada, Sergio A

    Nature cancer

    2020  Volume 1, Issue 12, Page(s) 1153–1166

    Abstract: Intratumoral regulatory T cell (Treg) abundance associates with diminished anti-tumor immunity and poor prognosis in human cancers. Recent work demonstrates that CD25, the high affinity receptor subunit for IL-2, is a selective target for Treg depletion ... ...

    Abstract Intratumoral regulatory T cell (Treg) abundance associates with diminished anti-tumor immunity and poor prognosis in human cancers. Recent work demonstrates that CD25, the high affinity receptor subunit for IL-2, is a selective target for Treg depletion in mouse and human malignancies; however, anti-human CD25 antibodies have failed to deliver clinical responses against solid tumors due to bystander IL-2 receptor signaling blockade on effector T cells, which limits their anti-tumor activity. Here we demonstrate potent single-agent activity of anti-CD25 antibodies optimized to deplete Tregs whilst preserving IL-2-STAT5 signaling on effector T cells, and demonstrate synergy with immune checkpoint blockade in vivo. Pre-clinical evaluation of an anti-human CD25 (RG6292) antibody with equivalent features demonstrates, in both non-human primates and humanized mouse models, efficient Treg depletion with no overt immune-related toxicities. Our data supports the clinical development of RG6292 and evaluation of novel combination therapies incorporating non-IL-2 blocking anti-CD25 antibodies in clinical studies.
    MeSH term(s) Animals ; Antibodies, Monoclonal/pharmacology ; Interleukin-2/pharmacology ; Mice ; Neoplasms ; Signal Transduction ; T-Lymphocytes, Regulatory
    Chemical Substances Antibodies, Monoclonal ; Interleukin-2
    Language English
    Publishing date 2020-11-09
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ISSN 2662-1347
    ISSN (online) 2662-1347
    DOI 10.1038/s43018-020-00133-0
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article ; Online: A novel approach to investigate the effect of methionine oxidation on pharmacokinetic properties of therapeutic antibodies.

    Stracke, Jan / Emrich, Thomas / Rueger, Petra / Schlothauer, Tilman / Kling, Lothar / Knaupp, Alexander / Hertenberger, Hubert / Wolfert, Andreas / Spick, Christian / Lau, Wilma / Drabner, Georg / Reiff, Ulrike / Koll, Hans / Papadimitriou, Apollon

    mAbs

    2014  Volume 6, Issue 5, Page(s) 1229–1242

    Abstract: Preserving the chemical and structural integrity of therapeutic antibodies during manufacturing and storage is a major challenge during pharmaceutical development. Oxidation of Fc methionines Met252 and Met428 is frequently observed, which leads to ... ...

    Abstract Preserving the chemical and structural integrity of therapeutic antibodies during manufacturing and storage is a major challenge during pharmaceutical development. Oxidation of Fc methionines Met252 and Met428 is frequently observed, which leads to reduced affinity to FcRn and faster plasma clearance if present at high levels. Because oxidation occurs in both positions simultaneously, their individual contribution to the concomitant changes in pharmacokinetic properties has not been clearly established. A novel pH-gradient FcRn affinity chromatography method was applied to isolate three antibody oxidation variants from an oxidized IgG1 preparation based on their FcRn binding properties. Physico-chemical characterization revealed that the three oxidation variants differed predominantly in the number of oxMet252 per IgG (0, 1, or 2), but not significantly in the content of oxMet428. Corresponding to the increase in oxMet252 content, stepwise reduction of FcRn affinity in vitro, as well as faster clearance and shorter terminal half-life, in huFcRn-transgenic mice were observed. A single Met252 oxidation per antibody had no significant effect on pharmacokinetics (PK) compared with unmodified IgG. Importantly, only molecules with both heavy chains oxidized at Met252 exhibited significantly faster clearance. In contrast, Met428 oxidation had no apparent negative effect on PK and even led to somewhat improved FcRn binding and slower clearance. This minor effect, however, seemed to be abrogated by the dominant effect of Met252 oxidation. The novel approach of functional chromatographic separation of IgG oxidation variants followed by physico-chemical and biological characterization has yielded the first experimentally-backed explanation for the unaltered PK properties of antibody preparations containing relatively high Met252 and Met428 oxidation levels.
    MeSH term(s) Animals ; Antibodies, Monoclonal/metabolism ; Antibodies, Monoclonal/pharmacokinetics ; Antibodies, Monoclonal/therapeutic use ; Antibody Affinity ; Chromatography, Affinity ; Female ; Histocompatibility Antigens Class I/genetics ; Histocompatibility Antigens Class I/metabolism ; Humans ; Hydrogen-Ion Concentration ; Immunoglobulin Fc Fragments/blood ; Immunoglobulin Fc Fragments/metabolism ; Immunoglobulin Fc Fragments/therapeutic use ; Metabolic Clearance Rate ; Methionine/metabolism ; Mice, Inbred C57BL ; Mice, Knockout ; Mice, Transgenic ; Oxidation-Reduction/drug effects ; Protein Binding ; Receptors, Fc/genetics ; Receptors, Fc/metabolism ; Spectrometry, Mass, Electrospray Ionization
    Chemical Substances Antibodies, Monoclonal ; Fc receptor, neonatal ; Histocompatibility Antigens Class I ; Immunoglobulin Fc Fragments ; Receptors, Fc ; Methionine (AE28F7PNPL)
    Language English
    Publishing date 2014
    Publishing country United States
    Document type Journal Article
    ISSN 1942-0870
    ISSN (online) 1942-0870
    DOI 10.4161/mabs.29601
    Database MEDical Literature Analysis and Retrieval System OnLINE

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