scholarly journals Antibody Humanization: Intra and Inter VH-VL Non-bond Energy Sort Best Humanized Antibody

2021 ◽  
Author(s):  
Qiang Zhong ◽  
Jizhong Lou
Keyword(s):  
Crystal Structure ◽  
Bond Energy ◽  
Experimental Dataset ◽  
Humanized Antibody ◽  
Computer Aided ◽  
Antibody Structure ◽  
Cdr Grafting ◽  
Antibody Drug ◽  
Grafting Onto

Antibody humanization of non-human derived antibody reduces immunogenicity of antibody drug. Computer aided antibody humanization has became an efficient and rapid routine process. Our computational humanization pipeline includes CDR grafting onto antibody crystal structure and humanization of CDR grafted antibody structure. Then, intra and inter VH-VL non-bond energy is calculated and sorted for selection best humanized antibody. Compare to experimental dataset, result indicate that intra and inter VH-VL non-bond energy could rank humanized antibody.

scholarly journals Antibody structure and engineering considerations for the design and function of Antibody Drug Conjugates (ADCs)

2017 ◽  
Vol 7 (3) ◽  
pp. e1395127 ◽  
Author(s):  
Ricarda M. Hoffmann ◽  
Ben G. T. Coumbe ◽  
Debra H. Josephs ◽  
Silvia Mele ◽  
Kristina M. Ilieva ◽  
...  
Keyword(s):  
Antibody Drug Conjugates ◽  
Drug Conjugates ◽  
Antibody Structure ◽  
And Function ◽  
Antibody Drug

Studies on the Catalytic Performance of the Nieuwland Catalyst and Anhydrous Catalyst in the Dimerization of Acetylene to Monovinylacetylene

2012 ◽  
Vol 550-553 ◽  
pp. 312-316 ◽  
Author(s):  
Jian Guo Liu ◽  
Ming Han Han ◽  
Zhan Wen Wang
Keyword(s):  
Crystal Structure ◽  
Electron Density ◽  
Bond Energy ◽  
Catalytic Performance ◽  
Similar Crystal Structure

The present work aimed to find reasons for different catalytic ability of the Nieuwland catalyst and anhydrous catalyst in dimerization of acetylene to produce Monovinylacetylene (MVA). The results showed the catalytic ions in the Nieuwland catalyst and the anhydrous catalyst were CuCl-2 and Cu2Cl-3 respectively by studies on the Cu-containing crystals recovered from corresponding catalyst. CuCl-2 in crystal A and Cu2Cl-3 in crystal B has similar crystal structure, however, Cu(Ι) in Cu2Cl-3 has higher electron density due to stronger bond energy of Cu(Ι)-Cl, which may contribute to the higher activity of the anhydrous catalyst than that of Nieuwland catalyst.

scholarly journals Multiplex LC-MS/MS Assays for Clinical Bioanalysis of MEDI4276, an Antibody-Drug Conjugate of Tubulysin Analogue Attached via Cleavable Linker to a Biparatopic Humanized Antibody against HER-2

Antibodies ◽  
2019 ◽  
Vol 8 (1) ◽  
pp. 11 ◽  
Author(s):  
Morse Faria ◽  
Marlking Peay ◽  
Brandon Lam ◽  
Eric Ma ◽  
Moucun Yuan ◽  
...  
Keyword(s):  
Bioanalytical Methods ◽  
Antibody Drug Conjugate ◽  
Humanized Antibody ◽  
Drug Conjugates ◽  
Additional Stability ◽  
Her 2 ◽  
High Concentrations ◽  
Cleavable Peptide ◽  
Drug Antibody Ratio ◽  
Antibody Drug

Bioanalysis of complex biotherapeutics, such as antibody-drug conjugates (ADCs), is challenging and requires multiple assays to describe their pharmacokinetic (PK) profiles. To enable exposure-safety and exposure-efficacy analyses, as well as to understand the metabolism of ADC therapeutics, three bioanalytical methods are typically employed: Total Antibody, Antibody Conjugated Toxin or Total ADC and Unconjugated Toxin. MEDI4276 is an ADC comprised of biparatopic humanized antibody attached via a protease-cleavable peptide-based maleimidocaproyl linker to a tubulysin toxin (AZ13599185) with an approximate average drug-antibody ratio of 4. The conjugated payload of MEDI4276 can undergo ester hydrolysis to produce the conjugated payload AZ13687308, leading to the formation of MEDI1498 (de-acetylated MEDI4276). In this report, we describe the development, validation and application of three novel multiplex bioanalytical methods. The first ligand-binding liquid chromatography coupled with tandem mass spectrometry (LBA-LC-MS/MS) method was developed and validated for simultaneous measurement of total antibody and total ADC (antibody-conjugated AZ13599185) from MEDI4276. The second LBA-LC-MS/MS assay quantified total ADC (antibody-conjugated AZ13687308) from MEDI1498. The third multiplex LC-MS/MS assay was used for simultaneous quantification of unconjugated AZ13599185 and AZ13687308. Additional stability experiments confirmed that quantification of the released warhead in the presence of high concentrations of MEDI4276 was acceptable. Subsequently, the assays were employed in support of a first-in-human clinical trial (NCT02576548).

Computer-Aided Design of Compounds with Crystal Structure of Melilites

2020 ◽  
Vol 11 (4) ◽  
pp. 787-794
Author(s):  
N. N. Kiselyova ◽  
V. A. Dudarev ◽  
V. V. Ryazanov ◽  
O. V. Sen’ko ◽  
A. A. Dokukin
Keyword(s):  
Crystal Structure ◽  
Computer Aided Design ◽  
Computer Aided ◽  
Aided Design
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