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The reverse engineering and rapid prototyping technology are used to analyze and improve the car interior handle. Digital information of the selected car interior handle are collected and sorted by hand-held laser scanner due to its structural characteristics. By the reverse design idea, the reconstruction of the inner handle surface and the 3D solid modeling are completed based on Imageware and SolidWorks software Finally, the car interior handle is obtained through rapid prototyping technology. The application of reverse engineering and rapid prototyping technology can greatly shorten the design and development cycle and effectively improve the design efficiency of products.

By taking desulfurization of liquid fuels as a demonstrative example, a bottom-up selection was performed to find the metal-organic frameworks (MOF)-type adsorbents with highly efficient adsorption performance of large molecules. Through carefully analyzing the adsorption mechanism for typical S-heterocyclic compounds like dibenzothiophene (DBT), PCN-10 was selected in consideration of the simultaneous inclusion of several kinds of interactions in the framework. Experimental results demonstrate that this MOF exhibits extraordinary high DBT adsorption capacity (75.24 mg S g−1), showing record uptake among all the reported porous materials for the removal of thiophenicsulfur from fuels (below 1000 ppmwS), to the best of our knowledge. Moreover, the removal rate for the low sulfur concentration (50 ppmwS) can reach beyond 99%. This strategy can be conveniently extended to the screening and design of MOFs for the efficient removal of other important large guest molecules. © 2016 American Institute of Chemical Engineers AIChE J, 62: 4491–4496, 2016

Trophoblast cell surface antigen 2 (Trop-2) is overexpressed on many epithelial carcinomas while having low levels of expression on normal tissue. Overexpression of Trop-2 has been correlated with poor prognosis in several solid tumors. Trop-2 is overexpressed in ~60% of gastric cancer, which causes more than 500,000 mortalities every year in China. We have developed a Trop-2 antibody-drug conjugate (ADC), BAT8003, that utilizes an anti-Trop-2 IgG1 antibody, engineered for site-specific conjugation, a novel uncleavable linker, and a potent maytansine derivative as the payload. Site-specific conjugation allows for a more controllable drug-antibody ratio (DAR), resulting in a more homogenous product. BAT8003 also incorporates increased ADCC effects through afucosylation to further enhance potency. Here we show that BAT8003 is internalized in Trop-2 positive cells. It inhibits proliferation of a number of different Trop2-overexpressed tumor cells with IC50s of ~1 nM. In a gastric cancer (NCI-N87) mouse xenograft model, BAT8003 demonstrates strong inhibition activity on tumor growth at doses of 5 mg/kg and 15 mg/kg. A multiple dose toxicity study in monkey reveals that the highest non-severely toxic dose (HNSTD) of BAT8003 is 20 mg/kg when dose once every 3 weeks. The preclinical profile of BAT8003 warrants further clinical development for the treatment of gastric cancer as well as other Trop-2 over-expressing cancers. Citation Format: Weijia Tang, Xingxing Mei, Ziqiang Ou, Jirong Gan, Shengfeng Li, Jin-Chen Yu. Development of a potent Trop-2 antibody-drug conjugate, BAT8003, for the treatment of Trop-2 positive gastric tumors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 4821.

T-DM1, an antibody drug conjugate (ADC), has been approved by FDA for patients with HER2-positive, metastatic breast cancer who previously received trastuzumab and a taxane. DM1 is released because it is connected to the linker of T-DM1 by a thio-ether bond, which can be broken via retro-Michael addition. To improve the antibody-drug stability, we created an anti-HER2 ADC (BAT8001) which used a novel uncleavable linker to connect trastuzumab and a payload of maytansine derivative. BAT8001 exhibits similar level of potency against proliferation of HER2-overexpressed cells as T-DM1 and demonstrates strong inhibition activity on tumor growth in both cell-line and patient-derived xenograft models. Pharmacokinetics (PK) study in monkey reveals BAT8001 has similar level of exposure, half-life, and Cmax as T-DM1. BAT8001 Ph1 clinical trial in patients with HER2+ late-stage breast cancer recently was completed. The clinical study used standard “3+3” multiple-dose escalation method, evaluated BAT8001 safety, PK and explored the efficacy. Twenty-nine subjects were randomized and 27 subjects received the treatment with escalated dose 1.2mg/kg, 2.4mg/kg,3.6mg/kg, 4.8mg/kg and 6.0mg/kg. Two subjects died during the screening time without treatment due to disease progression. Nineteen (79.2%) subjects completed at least 4-cycle treatment. The PK parameter (Cmax and AUC(0-t)) values demonstrated dose-dependent linear relationship. In the safety evaluation, the incidences of AE and AE with CTCAE >=3 increased when dose escalated. The platelet count decrease and AST elevation were found to be the most common and severe AEs. Three subjects had serious adverse events (SAE) of bone destruction which were considered to be not investigated-drug related by the PI. Among those 3 subjects, 2 subjects withdrew from the study due to the SAE and 1 subject continued the treatment. The preliminary efficacy assessment after 10 months treatment found that 1 (3.7%) patient exhibited the complete response (CR), 5 (18.5%) patients exhibited the partial responses (PR), and 5(18.5%) patients exhibited the stable diseases. Based on the information above, the dose of 3.6mg/kg achieved target drug exposure and was found to be the effective and well-tolerated, which was selected to be the dose in the confirmatory clinical trial. Currently, a Phase 3, multicenter, randomized, open-label, controlled trial evaluating the efficacy and safety of BAT8001 has been initiated in patients with HER2+ metastatic breast cancer who previously received trastuzumab separately or in combination with taxanes. The trial is designed to compare BAT8001 versus lapatinib combined with capecitabine which is 2nd-line standard of care for metastatic breast cancer patients in China. This Phase 3 trial plans to recruit approximately 410 patients and by Jan 2019 more than 130 patients have received the treatment of BAT8001. The BAT8001 benefit-risk profile continues to support further development and the clinical results will be revealed by early 2020. Citation Format: Shusen Wang, Fei Xu, Ruoxi Hong, Wen Xia, Jin-Chen Yu, Weijia Tang, Jin Wei, ShuQiang Song, Zhaohe Wang, Li Zhang, Shengfeng Li. BAT8001, a potent anti-HER2 antibody drug conjugate with a novel uncleavable linker to reduce toxicity for patients with HER2-positive tumor [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr CT053.