Shanghai, China
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The present invention provides a mutated antibody of the fully humanized HER2 antibody GB235-019, wherein the amino acid sequence of the heavy chain variable region and the amino acid sequence of the light chain variable region of the mutated antibody are respectively SEQ ID NO: 10, SEQ ID NO: 2; SEQ ID NO: 11, SEQ ID NO: 2; or SEQ ID NO:12, SEQ ID NO:2. The mutated antibody has the ability to specifically bind to human HER2 antigen, similar to the GB235-019 antibody. They can also be used in combination with additional HER2 positive tumor therapeutic agents for treating HER2 positive tumor, weakly positive tumor or negative tumor.


Patent
Genor Biopharma Co. | Date: 2017-01-11

The present invention provides a mutated antibody of the fully humanized HER2 antibody GB235-019, wherein the amino acid sequence of the heavy chain variable region and the amino acid sequence of the light chain variable region of the mutated antibody are respectively SEQ ID NO: 10, SEQ ID NO: 2; SEQ ID NO: 1 1, SEQ ID NO: 2; or SEQ ID NO:12, SEQ ID NO:2. The mutated antibody has the ability to specifically bind to human HER2 antigen, similar to the GB235-019 antibody. They can also be used in combination with additional HER2 positive tumor therapeutic agents for treating HER2 positive tumor, weakly positive tumor or negative tumor.


Xue J.-H.,Genor Biopharma Co. | Huang X.-Y.,Genor Biopharma Co. | Xu S.-Q.,Genor Biopharma Co.
Chinese Journal of Biologicals | Year: 2015

Objective: To develop a real-time quantitative PCR method for determination of copy number of light chain and heavy chain genes of foreign antibody in transgenic CHO cells. Methods: The standard curves of light and heavy chain genes were generated with the standard plasmids containing light and heavy chain genes respectively. The genomic DNA of CHO cells transfected with light chain and heavy chain genes were extracted and analyzed by real-time quantitative PCR. According to the number of single copy gene in 10 ng CHO genomic DNA, the copy number of light chain and heavy chain genes were calculated by the standard curve. Results: The standard curves for copy numbers of light and heavy chain genes were generated respectively, of which the correlation coefficients were more than 0. 99. The amplification efficiencies of light and heavy chain genes were 91. 6% and 91. 8% respectively, indicating good specificities of the curves. The copy numbers of light chain and heavy chain genes decreased simultaneously with the increasing passage of cultured cells. Conclusion: A real-time quantitative PCR method for determination of copy numbers of light and heavy chain genes was developed successfully, which might be used for the study on genetic stability of foreign antibody genes in CHO cells, and provided a test method for obtaining the cell lines for high expression.


Lin J.,Genor Biopharma Co. | Tan Q.,Genor Biopharma Co. | Wang S.,Genor Biopharma Co.
Journal of Separation Science | Year: 2011

Capillary isoelectric focusing (CIEF) is a common choice for separation and analysis of the charge variants and impurities of therapeutic proteins. In this study, we developed a sensitive CIEF analysis method for determining the charge heterogeneity of therapeutic monoclonal antibody (mAb) using Beckman PA800 plus platform. The mixture of 5% Pharmalyte 8-10.5 and 1% Pharmalyte 3-10 was used to overcome the limitation of using single Pharmalyte 3-10 in detecting charge heterogeneity of basic mAb. This approach largely improved the resolution of the heterogeneous peaks. In addition, 3 M urea and 50 mM arginine (Arg) were used to improve the separation as solubilizer and cathodic stabilizer, respectively. Under optimized condition, both acidic and basic peaks of the mAb were separated well. Method qualification results showed good specificity, precision, and linearity within the concentration range of 0.03-0.20 mg/mL for mAb R1. The method was then used for C-terminal lysine (Lys) variants characterization and glycosylation profiles analysis. Furthermore, it also had a wide application in the clone screening process. The highly sensitive and repeatable results highlighted the wide application prospects of this method in biopharmaceutical industry. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.


Xu Z.,Genor Biopharma Co. | Li J.,Genor Biopharma Co. | Zhou J.X.,Genor Biopharma Co.
Preparative Biochemistry and Biotechnology | Year: 2012

Aggregate removal is one of the most important aspects in monoclonal antibody (mAb) purification. Cation-exchange chromatography (CEX), a widely used polishing step in mAb purification, is able to clear both process-related impurities and product-related impurities. In this study, with the implementation of quality by design (QbD), a process development approach for robust removal of aggregates using CEX is described. First, resin screening studies were performed and a suitable CEX resin was chosen because of its relatively better selectivity and higher dynamic binding capacity. Second, a pH-conductivity hybrid gradient elution method for the CEX was established, and the risk assessment for the process was carried out. Third, a process characterization study was used to evaluate the impact of the potentially important process parameters on the process performance with respect to aggregate removal. Accordingly, a process design space was established. Aggregate level in load is the critical parameter. Its operating range is set at 0-3% and the acceptable range is set at 0-5%. Equilibration buffer is the key parameter. Its operating range is set at 40±5mM acetate, pH 5.0±0.1, and acceptable range is set at 40±10mM acetate, pH 5.0±0.2. Elution buffer, load mass, and gradient elution volume are non-key parameters; their operating ranges and acceptable ranges are equally set at 250±10mM acetate, pH 6.0±0.2, 45±10g/L resin, and 10±20% CV respectively. Finally, the process was scaled up 80 times and the impurities removal profiles were revealed. Three scaled-up runs showed that the size-exclusion chromatography (SEC) purity of the CEX pool was 99.8% or above and the step yield was above 92%, thereby proving that the process is both consistent and robust. © 2012 Taylor and Francis Group, LLC.


Liu M.,Beijing Institute of Biotechnology | Liu M.,East China University of Science and Technology | Liu M.,Genor Biopharma Co. | Wang S.,Beijing Institute of Biotechnology | And 5 more authors.
PLoS ONE | Year: 2012

Amylosucrase (AS) is a kind of glucosyltransferases (E.C. 2.4.1.4) belonging to the Glycoside Hydrolase (GH) Family 13. In the presence of an activator polymer, in vitro, AS is able to catalyze the synthesis of an amylose-like polysaccharide composed of only α-1,4-linkages using sucrose as the only energy source. Unlike AS, other enzymes responsible for the synthesis of such amylose-like polymers require the addition of expensive nucleotide-activated sugars. These properties make AS an interesting enzyme for industrial applications. In this work, the structures and topology of the two AS were thoroughly investigated for the sake of explaining the reason why Deinococcus geothermalis amylosucrase (DgAS) is more stable than Neisseria polysaccharea amylosucrase (NpAS). Based on our results, there are two main factors that contribute to the superior thermostability of DgAS. On the one hand, DgAS holds some good structural features that may make positive contributions to the thermostability. On the other hand, the contacts among residues of DgAS are thought to be topologically more compact than those of NpAS. Furthermore, the dynamics and unfolding properties of the two AS were also explored by the gauss network model (GNM) and the anisotropic network model (ANM). According to the results of GNM and ANM, we have found that the two AS could exhibit a shear-like motion, which is probably associated with their functions. What is more, with the discovery of the unfolding pathway of the two AS, we can focus on the weak regions, and hence designing more appropriate mutations for the sake of thermostability engineering. Taking the results on structure, dynamics and unfolding properties of the two AS into consideration, we have predicted some novel mutants whose thermostability is possibly elevated, and hopefully these discoveries can be used as guides for our future work on rational design. © 2012 Liu et al.


An anti-human RANKL antibody, a humanized antibody for the anti-human RANKL antibody, a pharmaceutical composition and a use thereof are provided. The anti-human RANKL antibody is capable of bonding specifically with an amino acid sequence of SEQ ID NO.1, a heavy chain of the anti-human RANKL antibody includes a variable region in one of amino acid sequences of SEQ ID NO.2-9, and a light chain of the anti-human RANKL antibody includes a variable region in one of amino acid sequences of SEQ ID NO.10-17. The humanized antibody is capable of bonding specifically with human RANKL, a variable region in a heavy chain of the humanized antibody is selected from amino acid sequences of SEQ ID NO.6, NO.23, NO.25, NO.27 or NO.29, and a variable region in a light chain of the humanized antibody is selected from amino acid sequences of SEQ ID NO.14, NO.31, NO.33, NO.35, NO.37 or NO.39.


A humanized the anti-human RANKL antibody, a pharmaceutical composition and a use thereof are provided. The humanized antibody is capable of bonding specifically with human RANKL, a variable region in a heavy chain of the humanized antibody is selected from amino acid sequences of SEQ ID NO: 6, NO: 23, NO: 25, NO: 27 or NO: 29, and a variable region in a light chain of the humanized antibody is selected from amino acid sequences of SEQ ID NO: 14, NO: 31, NO: 33, NO: 35, NO: 37 or NO: 39. Preferably, a complete heavy chain of the humanized antibody is selected from an amino acid sequence of one of SEQ ID NO: 46-50, and/or a complete light chain of the humanized antibody is selected from an amino acid sequence of one of SEQ ID NO: 51-56. The humanized antibody may be used for preparing a medication for the treatment of bone loss diseases.


Patent
Genor Biopharma Co. | Date: 2014-07-02

The present invention provides an anthropogenic glucagon-like peptide-1 (GLP-1) recombinant protein molecule fused with an anthropogenic immunoglobulin subtype (IgG2) Fc section and a preparation method and purpose thereof. The fusion protein has the biological activity of GLP-1, and also has a significantly prolonged half-life in vivo. The fusion protein can be used to treat type II diabetes, obesity, and other diseases that are treated by decreasing serum glucose, suppressing gastrointestinal motility, and emptying or suppressing food intake.


An anti-human RANKL antibody, a humanized antibody for the anti-human RANKL antibody, a pharmaceutical composition and a use thereof are provided. The anti-human RANKL antibody is capable of bonding specifically with an amino acid sequence of SEQ ID NO.1, a heavy chain of the anti-human RANKL antibody includes a variable region in one of amino acid sequences of SEQ ID NO.2-9, and a light chain of the anti-human RANKL antibody includes a variable region in one of amino acid sequences of SEQ ID NO.10-17. The humanized antibody is capable of bonding specifically with human RANKL, a variable region in a heavy chain of the humanized antibody is selected from amino acid sequences of SEQ ID NO.6, NO.23, NO.25, NO.27 or NO.29, and a variable region in a light chain of the humanized antibody is selected from amino acid sequences of SEQ ID NO.14, NO.31, NO.33, NO.35, NO.37 or NO.39.

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