AAPS Journal最新文献_第8页

Correction: Virtual Bioequivalence Assessment of Ritlecitinib Capsules with Incorporation of Observed Clinical Variability Using a Physiologically Based Pharmacokinetic Model. 更正：利用基于生理学的药代动力学模型，结合观察到的临床变异性，对瑞替西替尼胶囊进行虚拟生物等效性评估。

IF 4.5 3区医学

AAPS Journal Pub Date : 2024-02-21 DOI: 10.1208/s12248-024-00895-w

Anas Saadeddin, Vivek Purohit, Yeamin Huh, Mei Wong, Aurelia Maulny, Martin E Dowty, Kazuko Sagawa

引用次数: 0

Characterization of CYP3A5 Selective Inhibitors for Reaction Phenotyping of Drug Candidates. 用于候选药物反应表型分析的 CYP3A5 选择性抑制剂的特征。

IF 4.5 3区医学

AAPS Journal Pub Date : 2024-02-16 DOI: 10.1208/s12248-024-00894-x

Jie Chen, Lloyd Wei Tat Tang, Samantha Jordan, Makayla Harrison, Gabrielle M Gualtieri, Ethan DaSilva, Danial Morris, Gary Bora, Ye Che, Li Di

{"title":"Characterization of CYP3A5 Selective Inhibitors for Reaction Phenotyping of Drug Candidates.","authors":"Jie Chen, Lloyd Wei Tat Tang, Samantha Jordan, Makayla Harrison, Gabrielle M Gualtieri, Ethan DaSilva, Danial Morris, Gary Bora, Ye Che, Li Di","doi":"10.1208/s12248-024-00894-x","DOIUrl":"10.1208/s12248-024-00894-x","url":null,"abstract":"CYP3A is one of the most important classes of enzymes and is involved in the metabolism of over 70% drugs. While several selective CYP3A4 inhibitors have been identified, the search for a selective CYP3A5 inhibitor has turned out to be rather challenging. Recently, several selective CYP3A5 inhibitors have been identified through high-throughput screening of ~ 11,000 compounds and hit expansion using human recombinant enzymes. We set forth to characterize the three most selective CYP3A5 inhibitors in a more physiologically relevant system of human liver microsomes to understand if these inhibitors can be used for reaction phenotyping studies in drug discovery settings. Gomisin A and T-5 were used as selective substrate reactions for CYP3A4 and CYP3A5 to determine IC50 values of the two enzymes. The results showed that clobetasol propionate and loteprednol etabonate were potent and selective CYP3A5 reversible inhibitors with selectivity of 24-fold against CYP3A4 and 39-fold or more against the other major CYPs. The selectivity of difluprednate in HLM is much weaker than that in the recombinant enzymes due to hydrolysis of the acetate group in HLM. Based on the selectivity data, loteprednol etabonate can be utilized as an orthogonal approach, when experimental fraction metabolized of CYP3A5 is greater than 0.5, to understand CYP3A5 contribution to drug metabolism and its clinical significance. Future endeavors to identify even more selective CYP3A5 inhibitors are warranted to enable accurate determination of CYP3A5 contribution to metabolism versus CYP3A4.","PeriodicalId":50934,"journal":{"name":"AAPS Journal","volume":"26 2","pages":"26"},"PeriodicalIF":4.5,"publicationDate":"2024-02-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139747745","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Taurine, a Naturally Occurring Amino Acid, as a Physical Stability Enhancer of Different Monoclonal Antibodies. 天然氨基酸牛磺酸作为不同单克隆抗体的物理稳定性增强剂

IF 4.5 3区医学

AAPS Journal Pub Date : 2024-02-14 DOI: 10.1208/s12248-024-00893-y

Shravan Sreenivasan, Anurag S Rathore

{"title":"Taurine, a Naturally Occurring Amino Acid, as a Physical Stability Enhancer of Different Monoclonal Antibodies.","authors":"Shravan Sreenivasan, Anurag S Rathore","doi":"10.1208/s12248-024-00893-y","DOIUrl":"10.1208/s12248-024-00893-y","url":null,"abstract":"Degradation of therapeutic monoclonal antibodies (mAbs) is a major concern as it affects efficacy, shelf-life, and safety of the product. Taurine, a naturally occurring amino acid, is investigated in this study as a potential mAb stabilizer with an extensive analytical characterization to monitor product degradation. Forced degradation of trastuzumab biosimilar (mAb1)-containing samples by thermal stress for 30 min resulted in high-molecular-weight species by more than 65% in sample without taurine compared to the sample with taurine. Samples containing mAb1 without taurine also resulted in higher Z-average diameter, altered protein structure, higher hydrophobicity, and lower melting temperature compared to samples with taurine. The stabilizing effect of taurine was retained at different mAb and taurine concentrations, time, temperatures, and buffers, and at the presence of polysorbate 80 (PS80). Even the lowest taurine concentration (10 mM) considered in this study, which is in the range of taurine levels in amino acid injections, resulted in enhanced mAb stability. Taurine-containing samples resulted in 90% less hemolysis than samples containing PS80. Additionally, mAb in the presence of taurine showed enhanced stability upon subjecting to stress with light of 365 nm wavelength, combination of light and H2O2, and combination of Fe2+ and H2O2, as samples containing mAb without taurine resulted in increased degradation products by more than 50% compared to samples with taurine upon subjecting to these stresses for 60 min. In conclusion, the presence of taurine enhanced physical stability of mAb by preventing aggregate formation, and the industry can consider it as a new mAb stabilizer.","PeriodicalId":50934,"journal":{"name":"AAPS Journal","volume":"26 1","pages":"25"},"PeriodicalIF":4.5,"publicationDate":"2024-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139736602","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Recommendations for Method Development and Validation of qPCR and dPCR Assays in Support of Cell and Gene Therapy Drug Development. 支持细胞和基因治疗药物开发的 qPCR 和 dPCR 检测方法开发和验证建议。

IF 4.5 3区医学

AAPS Journal Pub Date : 2024-02-05 DOI: 10.1208/s12248-023-00880-9

Amanda Hays, Mark Wissel, Kelly Colletti, Russell Soon, Mitra Azadeh, Justin Smith, Rajitha Doddareddy, Melanie Chalfant, Wendy Adamowicz, Swarna Suba Ramaswamy, Sanjay L Dholakiya, Sebastian Guelman, Bryan Gullick, Jennifer Durham, Keith Rennier, Pruthvi Nagilla, Anamica Muruganandham, Manisha Diaz, Cassandra Tierney, Kaarthik John, Jenny Valentine, Timothy Lockman, Hsing-Yin Liu, Benjamin Moritz, Jean Paul Ouedraogo, Marie-Soleil Piche, Muriel Smet, Jacqueline Murphy, Kaylyn Koenig, Agnes Zybura, Carrie Vyhlidal, Jonathan Mercier, Niketa Jani, Mikael Kubista, Donald Birch, Karlin Morse, Oskar Johansson

{"title":"Recommendations for Method Development and Validation of qPCR and dPCR Assays in Support of Cell and Gene Therapy Drug Development.","authors":"Amanda Hays, Mark Wissel, Kelly Colletti, Russell Soon, Mitra Azadeh, Justin Smith, Rajitha Doddareddy, Melanie Chalfant, Wendy Adamowicz, Swarna Suba Ramaswamy, Sanjay L Dholakiya, Sebastian Guelman, Bryan Gullick, Jennifer Durham, Keith Rennier, Pruthvi Nagilla, Anamica Muruganandham, Manisha Diaz, Cassandra Tierney, Kaarthik John, Jenny Valentine, Timothy Lockman, Hsing-Yin Liu, Benjamin Moritz, Jean Paul Ouedraogo, Marie-Soleil Piche, Muriel Smet, Jacqueline Murphy, Kaylyn Koenig, Agnes Zybura, Carrie Vyhlidal, Jonathan Mercier, Niketa Jani, Mikael Kubista, Donald Birch, Karlin Morse, Oskar Johansson","doi":"10.1208/s12248-023-00880-9","DOIUrl":"10.1208/s12248-023-00880-9","url":null,"abstract":"The emerging use of qPCR and dPCR in regulated bioanalysis and absence of regulatory guidance on assay validations for these platforms has resulted in discussions on lack of harmonization on assay design and appropriate acceptance criteria for these assays. Both qPCR and dPCR are extensively used to answer bioanalytical questions for novel modalities such as cell and gene therapies. Following cross-industry conversations on the lack of information and guidelines for these assays, an American Association of Pharmaceutical Scientists working group was formed to address these gaps by bringing together 37 industry experts from 24 organizations to discuss best practices to gain a better understanding in the industry and facilitate filings to health authorities. Herein, this team provides considerations on assay design, development, and validation testing for PCR assays that are used in cell and gene therapies including (1) biodistribution; (2) transgene expression; (3) viral shedding; (4) and persistence or cellular kinetics of cell therapies.","PeriodicalId":50934,"journal":{"name":"AAPS Journal","volume":"26 1","pages":"24"},"PeriodicalIF":4.5,"publicationDate":"2024-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139693516","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

An Explanation of Why Dose-Corrected Area Under the Curve for Alternate Administration Routes Can Be Greater than for Intravenous Dosing. 替代给药途径的剂量校正曲线下面积可能大于静脉给药的原因解析。

IF 4.5 3区医学

AAPS Journal Pub Date : 2024-01-30 DOI: 10.1208/s12248-024-00887-w

Hirokazu Wakuda, Yue Xiang, Jasleen K Sodhi, Naoto Uemura, Leslie Z Benet

{"title":"An Explanation of Why Dose-Corrected Area Under the Curve for Alternate Administration Routes Can Be Greater than for Intravenous Dosing.","authors":"Hirokazu Wakuda, Yue Xiang, Jasleen K Sodhi, Naoto Uemura, Leslie Z Benet","doi":"10.1208/s12248-024-00887-w","DOIUrl":"10.1208/s12248-024-00887-w","url":null,"abstract":"It is generally believed that bioavailability (F) calculated based on systemic concentration area under the curve (AUC) measurements cannot exceed 1.0, yet some published studies report this inconsistency. We teach and believe, based on differential equation derivations, that rate of absorption has no influence on measured systemic clearance following an oral dose, i.e., determined as available dose divided by AUC. Previously, it was thought that any difference in calculating F from urine data versus that from systemic concentration AUC data was due to the inability to accurately measure urine data. A PubMed literature search for drugs exhibiting F > 1.0 and studies for which F was measured using both AUC and urinary excretion dose-corrected analyses yielded data for 35 drugs. We show and explain, using Kirchhoff's Laws, that these universally held concepts concerning bioavailability may not be valid in all situations. Bioavailability, determined using systemic concentration measurements, for many drugs may be overestimated since AUC reflects not only systemic elimination but also absorption rate characteristics, which is most easily seen for renal clearance measures. Clearance of drug from the absorption site must be significantly greater than clearance following an iv bolus dose for F(AUC) to correctly correspond with F(urine). The primary purpose of this paper is to demonstrate that studies resulting in F > 1.0 and/or greater systemic vs urine bioavailability predictions may be accurate. Importantly, these explications have no significant impact on current regulatory guidance for bioequivalence testing, nor on the use of exposure (AUC) measures in making drug dosing decisions.","PeriodicalId":50934,"journal":{"name":"AAPS Journal","volume":"26 1","pages":"22"},"PeriodicalIF":4.5,"publicationDate":"2024-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139643303","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Successful Development of Nonclinical Anti-Drug Antibody Assays to Support Zinpentraxin Alfa Reproductive Toxicology Studies. 成功开发非临床抗药抗体测定，支持 Zinpentraxin Alfa 生殖毒理学研究。

IF 4.5 3区医学

AAPS Journal Pub Date : 2024-01-24 DOI: 10.1208/s12248-024-00891-0

Audrey Arjomandi, Ketevan Siradze, Melissa Cheu, Teresa Davancaze, Rajbharan Yadav, Gautham K Rao, Lisa Wong, Saloumeh K Fischer

{"title":"Successful Development of Nonclinical Anti-Drug Antibody Assays to Support Zinpentraxin Alfa Reproductive Toxicology Studies.","authors":"Audrey Arjomandi, Ketevan Siradze, Melissa Cheu, Teresa Davancaze, Rajbharan Yadav, Gautham K Rao, Lisa Wong, Saloumeh K Fischer","doi":"10.1208/s12248-024-00891-0","DOIUrl":"10.1208/s12248-024-00891-0","url":null,"abstract":"Immunogenicity assessment is an essential part of biotherapeutic drug development. While the immune response in animals is not always representative of the human immune response, immunogenicity data obtained in animal models is still informative for the evaluation of drug exposure and safety. The most common assay format used for the detection of anti-drug antibodies (ADAs) in preclinical and clinical studies is the bridging format. The advantage of this method is that it can detect all antibody isotypes generated against the therapeutic. However, the method development can be time-consuming and labor-intensive, due to the need for labeling of the drug which is used both as capture and detection. Various generic ADA assays have been successfully implemented to overcome these disadvantages and to enable faster assay development timelines to support nonclinical toxicology studies. Here, we describe the challenges in the development of an assay to detect antibodies to zinpentraxin alfa, a recombinant human pentraxin-2, in rabbit and rat toxicology studies. Our initial efforts to develop a bridging assay failed, prompting us to develop a method adapted from generic assay formats to detect anti-zinpentraxin alfa antibodies in the serum of different species with minimal optimization. However, while the general assay format remained similar, assay reagents were adapted between the different species, resulting in the development of two distinct assays for the detection of ADAs in rat and rabbit. Here, we share the final development/validation data and the immunogenicity study results. Our work highlights the need for the evaluation of alternate assay formats when evaluating novel drug modalities.","PeriodicalId":50934,"journal":{"name":"AAPS Journal","volume":"26 1","pages":"16"},"PeriodicalIF":4.5,"publicationDate":"2024-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139547650","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Virtual Bioequivalence Assessment of Ritlecitinib Capsules with Incorporation of Observed Clinical Variability Using a Physiologically Based Pharmacokinetic Model. 利用基于生理学的药代动力学模型，结合观察到的临床变异性对瑞替西替尼胶囊进行虚拟生物等效性评估

IF 4.5 3区医学

AAPS Journal Pub Date : 2024-01-24 DOI: 10.1208/s12248-024-00888-9

Anas Saadeddin, Vivek Purohit, Yeamin Huh, Mei Wong, Aurelia Maulny, Martin E Dowty, Kazuko Sagawa

{"title":"Virtual Bioequivalence Assessment of Ritlecitinib Capsules with Incorporation of Observed Clinical Variability Using a Physiologically Based Pharmacokinetic Model.","authors":"Anas Saadeddin, Vivek Purohit, Yeamin Huh, Mei Wong, Aurelia Maulny, Martin E Dowty, Kazuko Sagawa","doi":"10.1208/s12248-024-00888-9","DOIUrl":"10.1208/s12248-024-00888-9","url":null,"abstract":"Ritlecitinib, an orally available Janus kinase 3 and tyrosine kinase inhibitor being developed for the treatment of alopecia areata (AA), is highly soluble across the physiological pH range at the therapeutic dose. As such, it is expected to dissolve rapidly in any in vitro dissolution conditions. However, in vitro dissolution data showed slower dissolution for 100-mg capsules, used for the clinical bioequivalence (BE) study, compared with proposed commercial 50-mg capsules. Hence, a biowaiver for the lower 50-mg strength using comparable multimedia dissolution based on the f2 similarity factor was not possible. The in vivo relevance of this observed in vitro dissolution profile was evaluated with a physiologically based pharmacokinetic (PBPK) model. This report describes the development, verification, and application of the ritlecitinib PBPK model to translate observed in vitro dissolution data to an in vivo PK profile for ritlecitinib capsule formulations. Virtual BE (VBE) trials were conducted using the Simcyp VBE module, including the model-predicted within-subject variability or intra-subject coefficient of variation (ICV). The results showed the predicted ICV was predicted to be smaller than observed clinical ICV, resulting in a more optimistic BE risk assessment. Additional VBE assessment was conducted by incorporating clinically observed ICV. The VBE trial results including clinically observed ICV demonstrated that proposed commercial 50-mg capsules vs clinical 100-mg capsules were bioequivalent, with > 90% probability of success. This study demonstrates a PBPK model-based biowaiver for a clinical BE study while introducing a novel method to integrate clinically observed ICV into VBE trials with PBPK models. Trial registration: NCT02309827, NCT02684760, NCT04004663, NCT04390776, NCT05040295, NCT05128058.","PeriodicalId":50934,"journal":{"name":"AAPS Journal","volume":"26 1","pages":"17"},"PeriodicalIF":4.5,"publicationDate":"2024-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139547656","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Connexin-Containing Vesicles for Drug Delivery. 用于药物输送的含连接蛋白的囊泡

IF 4.5 3区医学

AAPS Journal Pub Date : 2024-01-24 DOI: 10.1208/s12248-024-00889-8

Mahmoud S Hanafy, Zhengrong Cui

引用次数: 0

Using Mechanistic Modeling Approaches to Support Bioequivalence Assessments for Oral Products. 使用机理建模方法支持口服产品的生物等效性评估。

IF 4.5 3区医学

AAPS Journal Pub Date : 2024-01-24 DOI: 10.1208/s12248-024-00886-x

Fang Wu, Youssef Mousa, Rebeka Jereb, Hannah Batchelor, Sumon Chakraborty, Tycho Heimbach, Ethan Stier, Filippos Kesisoglou, Sivacharan Kollipara, Lei Zhang, Liang Zhao

{"title":"Using Mechanistic Modeling Approaches to Support Bioequivalence Assessments for Oral Products.","authors":"Fang Wu, Youssef Mousa, Rebeka Jereb, Hannah Batchelor, Sumon Chakraborty, Tycho Heimbach, Ethan Stier, Filippos Kesisoglou, Sivacharan Kollipara, Lei Zhang, Liang Zhao","doi":"10.1208/s12248-024-00886-x","DOIUrl":"10.1208/s12248-024-00886-x","url":null,"abstract":"This report summarizes the proceedings for Day 1 Session 3 of the 2-day public workshop entitled \"Best Practices for Utilizing Modeling Approaches to Support Generic Product Development,\" a jointly sponsored workshop by the US Food and Drug Administration (FDA) and the Center for Research on Complex Generics (CRCG) in the year 2022. The aims of this workshop were to discuss how to modernize approaches for efficiently demonstrating bioequivalence (BE), to establish their role in modern paradigms of generic drug development, and to explore and develop best practices for the use of modeling and simulation approaches in regulatory submissions and approval. The theme of this session is mechanistic modeling approaches supporting BE assessments for oral drug products. As a summary, with more successful cases of PBPK absorption modeling being developed and shared, the general strategies/frameworks on using PBPK for oral products are being formed; this will help further evolvement of this area. In addition, the early communications between the industry and the agency through appropriate pathways (e.g., pre-abbreviated new drug applications (pre-ANDA) meetings) are encouraged, and this will speed up the successful development and utility of PBPK modeling for oral products.","PeriodicalId":50934,"journal":{"name":"AAPS Journal","volume":"26 1","pages":"19"},"PeriodicalIF":4.5,"publicationDate":"2024-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139547653","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Screening Non-neutralizing Anti-idiotype Antibodies Against a Drug Candidate for Total Pharmacokinetic and Target Engagement Assay. 筛选针对候选药物的非中和抗原型抗体，用于总药效学和靶点参与测定。

IF 4.5 3区医学

AAPS Journal Pub Date : 2024-01-24 DOI: 10.1208/s12248-024-00892-z

Veronica Liu, Kelly McGrath, Josh Albert, Andrew P Mayer, Maria Busz, Mary Birchler, Huaping Tang, Yong Jiang

{"title":"Screening Non-neutralizing Anti-idiotype Antibodies Against a Drug Candidate for Total Pharmacokinetic and Target Engagement Assay.","authors":"Veronica Liu, Kelly McGrath, Josh Albert, Andrew P Mayer, Maria Busz, Mary Birchler, Huaping Tang, Yong Jiang","doi":"10.1208/s12248-024-00892-z","DOIUrl":"10.1208/s12248-024-00892-z","url":null,"abstract":"Non-neutralizing anti-idiotype antibodies against a therapeutic monoclonal antibody (mAb) play a crucial role in the creation of total pharmacokinetic (PK) assays and total target engagement (TE) assays during both pre-clinical and clinical development. The development of these anti-idiotype antibodies is challenging. In this study, we utilized a hybridoma platform to produce a variety of anti-idiotype antibodies against GSK2857914, a humanized IgG1 anti-BCMA monoclonal antibody. The candidate clones were evaluated using surface plasmon resonance (SPR) and bio-layer interferometry (BLI) for binding affinity, binding profiling, matrix interference, and antibody pairing determination. We discovered that three anti-idiotype antibodies did not prevent BCMA from binding to GSK2857914. All three candidates demonstrated high binding affinities. One of the three exhibited minimal matrix inference and could pair with the other two candidates. Additionally, one of the three clones was biotinylated as a capture reagent for the total PK assay, and another was labeled with ruthenium as a detection reagent for both the total PK assay and total TE assay. The assay results clearly show that these reagents are genuine non-neutralizing anti-idiotypic antibodies and are suitable for total PK and TE assay development. Based on this and similar studies, we conclude that the hybridoma platform has a high success rate for generating non-neutralizing anti-idiotype antibodies. Our methodology for developing and characterizing non-neutralizing anti-idiotype antibodies to therapeutic antibodies can be generally applied to any antibody-based drug candidate's total PK and total TE assay development.","PeriodicalId":50934,"journal":{"name":"AAPS Journal","volume":"26 1","pages":"18"},"PeriodicalIF":4.5,"publicationDate":"2024-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139547647","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0