Chengdu Kanghong Biotechnology Inc.

Chengdu, China

Chengdu Kanghong Biotechnology Inc.

Chengdu, China
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Qu J.,Peking University | Cheng Y.,Peking University | Li X.,Peking University | Yu L.,Chengdu Kanghong Biotechnology Inc | Ke X.,Chengdu Kanghong Biotechnology Inc
Retina | Year: 2016

Purpose: To evaluate the efficacy of different doses of conbercept in patients with polypoidal choroidal vasculopathy in the AURORA study. Methods: Retrospective subgroup analyses of 12-month data from the AURORA study. Fifty-three patients (32 in 0.5-mg group and 21 in 2.0-mg group) diagnosed with polypoidal choroidal vasculopathy in AURORA study were retrospectively evaluated. Efficacy outcomes were compared between the two dosage groups. Results: At Month 12, mean changes in best-corrected visual acuity from baseline were 14.4 ± 14.1 letter scores for the 0.5-mg group and 14.2 ± 21.0 letter scores for the 2.0-mg group; mean central retinal thickness decreased by 104.5 ± 127.3 m in the 0.5-mg group and 140.7 ± 127.9 m in the 2.0-mg group; mean total macular volume decreased by 0.9 ± 2.3 mm 3 and 1.0 ± 1.2 mm 3 in the 0.5-mg and 2.0-mg groups, respectively. The mean subretinal fluid thickness decreased by 111.9 ± 122.5 m and 76.3 ± 112.6 m in the 0.5-mg and 2.0-mg groups, respectively. The mean pigment epithelial detachment height decreased by 79.3 ± 217.8 m and 61.3 ± 161.5 m in the 0.5-mg and 2.0-mg groups, respectively. The mean area of polyps decreased by 0.46 ± 0.76 mm 2 and 0.55 ± 1.34 mm 2 in the 0.5-mg and 2.0-mg groups, respectively. The mean total lesion area decreased by 2.51 ± 5.94 mm 2 (P 0.088) and 4.62 ± 5.51 mm 2 in the 0.5-mg group and 2.0-mg groups, respectively. Complete regression of polyps was observed in 56.5% of patients in the 0.5-mg group and 52.9% of those in the 2.0-mg group, whereas partial regression was observed in 26.1% and 35.3% of patients in the 0.5-mg and 2.0-mg groups, respectively. Conclusion: Intravitreal injection of conbercept appears to significantly improve visual acuity and anatomical outcomes in patients with polypoidal choroidal vasculopathy. © Copyright by Ophthalmic Communications Society, Inc.

Wu Z.,Chengdu Kanghong Biotechnology Inc. | Zhou P.,University of Electronic Science and Technology of China | Li X.,Peking University | Wang H.,Beijing Institute of Microbiology and Epidemiology | And 4 more authors.
PLoS ONE | Year: 2013

Conbercept is a genetically engineered homodimeric protein for the treatment of wet age-related macular degeneration (wet AMD) that functions by blocking VEGF-family proteins. Its huge, highly variable architecture makes characterization and development of a functional assay difficult. In this study, the primary structure, number of disulfide linkages and glycosylation state of conbercept were characterized by high-performance liquid chromatography, mass spectrometry, and capillary electrophoresis. Molecular modeling was then applied to obtain the spatial structural model of the conbercept-VEGF-A complex, and to study its inter-atomic interactions and dynamic behavior. This work was incorporated into a platform useful for studying the structure of conbercept and its ligand binding functions. © 2013 Wu et al.

Li X.,Peking University | Xu G.,Fudan University | Wang Y.,Xijing University | Xu X.,Shanghai First Peoples Hospital | And 8 more authors.
Ophthalmology | Year: 2014

Purpose To assess the safety and efficacy of multiple injections of 0.5 and 2.0 mg conbercept using variable dosing regimens in patients with neovascular age-related macular degeneration (AMD). Design Randomized, double-masked, multicenter, controlled-dose, and interval-ranging phase 2 clinical trial divided into a 3-month loading phase followed by a maintenance phase. Participants Patients with choroidal neovascularization secondary to AMD with lesion sizes of 12 disc areas or less and a best-corrected visual acuity (BCVA) letter score of between 73 and 24 were enrolled. Methods Patients were randomized 1:1 to receive either 0.5 or 2.0 mg intravitreal conbercept for 3 consecutive monthly does. After the third dose, each group was reassigned randomly again to monthly (Q1M group) or as-needed (pro re nata [PRN] group) treatment without changing the drug assignment. Main Outcome Measures The primary end point was the mean change in BCVA from baseline to month 3, with secondary end points being the mean change in BCVA, mean change in central retinal thickness (CRT), and safety at month 12. Results We enrolled 122 patients. At the primary end point at month 3, mean improvements in BCVA from baseline in the 0.5- and 2.0-mg groups were 8.97 and 10.43 letters, respectively. At month 12, mean improvements in BCVA from baseline were 14.31, 9.31, 12.42, and 15.43 letters for the 0.5-mg PRN, 0.5-mg Q1M, 2.0-mg PRN, and 2.0-mg Q1M regimens, respectively. At month 12, mean reductions in CRT in the 4 regimens were 119.8, 129.7, 152.1, and 170.8 μm, respectively. There were no significant differences for the pairwise comparisons between all study groups. The difference in the number of injections between the 2 PRN groups was not statistically significant. Treatment with conbercept generally was safe and well tolerated. Conclusions The significant gains in BCVA at 3 months were the same or better at 12 months in all conbercept dosing groups of neovascular AMD patients. During the 12 months, repeated intravitreal injections of conbercept were well tolerated in these patients. Future clinical trials are required to confirm its long-term efficacy and safety. © 2014 by the American Academy of Ophthalmology.

Li H.,Chengdu Medical College | Li H.,Chengdu Kanghong Biotechnology Co. | Lei N.,University of Sichuan | Lei N.,Chengdu University of Technology | And 4 more authors.
Experimental Eye Research | Year: 2012

Conbercept(KH902), a recombinant fusion protein in clinical trial II/III, shows good potential to treat the neovascular age-related macular degeneration (AMD). This investigation evaluated its ocular pharmacokinetics and pharmacodynamic profile in rabbits following intravitreal administration (IVT). Rabbits (n = 120) received single bilateral conbercept IVT administration or single IV administration. Conbercept concentrations in ocular tissues and serum were measured after dosing. VEGF concentration was also measured simultaneously. The results showed that conbercept rapidly distributed from vitreous into targeted tissues and lasted over 81 days. Clearance in ocular tissues was parallel and exhibited a terminal half of 2.5-4.2 days. The drug exposure in the retina was 1/4 to 1/5 of that in vitreous. Serum conbercept concentrations after IVT dosing were low and bioavailability was approximately 44%. And single intravitreal injection induced that ocular VEGF concentration declined over 60 days and serum VEGF concentration decreased for a short time but rebounded to higher level than baseline later. All these indicated conbercept good pharmacokinetic profile in rabbits, with good ocular tropism and systemic tolerance. Combined with the efficacy data from our earlier . in vitro and . in vivo studies, it should have a promising clinical application for AMD treatment. © 2011.

Teng L.-S.,Zhejiang University | Jin K.-T.,Zhejiang University | Jin K.-T.,Zhuji Hospital | He K.-F.,Zhejiang University | And 3 more authors.
Journal of the Chinese Medical Association | Year: 2010

Despite great efforts and resources being devoted to treatment, the incidence and mortality of numerous cancers have not decreased in recent decades. This is a result of the resistance of cancer cells to chemotherapeutic agents and radio-therapy. The development of antiangiogenic agents that target vascular endothelial growth factor (VEGF) provides a new option for treatment of cancer. Major advances have been achieved with cancer therapy based on antiangiogenic VEGF-targeted agents in the past few years, and some of the recently approved therapies are now being used in daily clinical practice. A further challenge is finding a more efficacious combination of antiangiogenic VEGF-targeted therapies and conventional radio- and chemotherapies. This review outlines the current preclinical and clinical cancer treatments using optimized combinations of antiangiogenic VEGF-targeted agents and conventional radiochemotherapy and highlights that better scheduling for the combination of radiochemotherapy and antiangiogenic VEGF-targeted agents should be developed to achieve better treatment outcomes. © 2010 Elsevier.

Wang Q.,Beijing Institute of Microbiology and Epidemiology | Li T.,Beijing Institute of Microbiology and Epidemiology | Wu Z.,Chengdu Kanghong Biotechnology Co. | Wu Q.,Chengdu Kanghong Biotechnology Co. | And 3 more authors.
PLoS ONE | Year: 2013

VEGF family factors are known to be the principal stimulators of abnormal angiogenesis, which play a fundamental role in tumor and various ocular diseases. Inhibition of VEGF is widely applied in antiangiogenic therapy. Conbercept is a novel decoy receptor protein constructed by fusing VEGF receptor 1 and VEGF receptor 2 extracellular domains with the Fc region of human immunoglobulin. In this study, we systematically evaluated the binding affinity of conbercept with VEGF isoforms and PlGF by using anti-VEGF antibody (Avastin) as reference. BIACORE and ELISA assay results indicated that conbercept could bind different VEGF-A isoforms with higher affinity than reference. Furthermore, conbercept could also bind VEGF-B and PlGF, whereas Avastin showed no binding. Oxygen-induced retinopathy model showed that conbercept could inhibit the formation of neovasularizations. In tumor-bearing nude mice, conbercept could also suppress tumor growth very effectively in vivo. Overall, our study have demonstrated that conbercept could bind with high affinity to multiple VEGF isoforms and consequently provide remarkable anti-angiogenic effect, suggesting the possibility to treat angiogenesis-related diseases such as cancer and wet AMD etc. © 2013 Wang et al.

Huang J.,Sun Yat Sen University | Li X.,Southern Medical University | Li M.,Sun Yat Sen University | Li S.,Sun Yat Sen University | And 7 more authors.
Diabetes, Obesity and Metabolism | Year: 2012

Aims: KH902 is a fusion protein that can bind vascular endothelial growth factor (VEGF) and placental growth factor (PlGF) through its binding ligand taken from the domains of VEGF receptor 1 and VEGF receptor 2 (VEGFR2). This study was to investigate the effects of intravitreal injection of KH902 on the retinas of streptozotocin-induced diabetic rats. Methods: Two weeks after induction of diabetes, the left eyes of diabetic rats in each group received an intravitreal injection of phosphate-buffered saline (PBS), Avastin or KH902 solution, respectively. Four weeks after intravitreal injection, retinal electrophysiological function and the integrity of inner blood retinal barrier (iBRB) were measured by electroretinogram and Evans blue perfusion. The protein levels of VEGF signal pathway were assayed by western blot. The expression and distribution of claudin-5 and occludin were analysed by double immunofluorescent staining under confocal microscope. The expression of VEGFR2 and PlGF was measured by immunohistochemistry. Results: Four weeks after intravitreal injection, KH902-treated rats had better retinal electrophysiological function, less retinal vessel leakage and lower levels of VEGFR2, PI3K, AKT, p-AKT, p-ERK and p-SRC than PBS or Avastin-treated rats. The distribution of claudin-5 and occludin in the retinal vessels of diabetic rats treated by KH902 was smoother and more uniform than those of diabetic rats treated by PBS or Avastin. The expression of PlGF and VEGFR2 in KH902-treated rats was decreased compared with those in PBS or Avastin-treated rats. Conclusions: KH902 could improve retinal electrophysiological function and inhibit the breakdown of iBRB by inhibiting the expression of VEGFR2, PlGF and PI3K, and the activation of SRC, AKT and ERK. © 2012 Blackwell Publishing Ltd.

Chen X.,Sun Yat Sen University | Li J.,Shandong University | Li M.,Sun Yat Sen University | Zeng M.,Sun Yat Sen University | And 8 more authors.
Diabetes, Obesity and Metabolism | Year: 2013

Aims: Vascular endothelial growth factor (VEGF) and placental growth factor (PlGF) are upregulated in many ocular neovascular diseases such as diabetic retinopathy (DR). KH902 is a recombinant fusion protein with its binding ligand taken from the domains of VEGF receptor-1 (VEGFR-1) and VEGF receptor-2 (VEGFR-2) and can bind all VEGF-A isoforms and PlGF. The aim of this study was to investigate the underlying mechanisms of anti-angiogenic effects of KH902. Methods: The toxic effect of KH902 on cultured human retinal endothelial cells (HRECs) was measured by Annexin V/PI staining and MTT assay. The concentrations of secreted VEGF and PlGF were measured by ELISA. The migration of HRECs was assessed by scratch wound and transwell assay. The sprouting of HRECs was determined by tube formation assay. The protein levels of Src, p-Src, PI3K, Akt1, p-Akt1, Erk1/2 and p-Erk1/2 were measured by Western blot. Results: KH902 at the concentrations from 100ng/ml to 100μg/ml had no cytotoxicity to cultured HRECs. KH902 bound not only VEGF165, but also PlGF that were secreted by HRECs under high glucose condition. A 500ng/ml of KH902 significantly suppressed high glucose-induced migration and sprouting of HRECs through downregulating the expression of PI3K and inhibiting the activation of Src, Akt1 and Erk1/2. Conclusion: Our study indicates that KH902 suppresses high glucose-induced migration and sprouting of HRECs through not only binding VEGF, but also PlGF to inhibit the activation of Src-Akt1-Erk1/2 pathway. KH902 is a drug that potentially inhibits angiogenic pathways involving in DR or other ocular neovascular diseases. © 2012 Blackwell Publishing Ltd.

Li T.,Sun Yat Sen University | Hu A.,Sun Yat Sen University | Li S.,Sun Yat Sen University | Luo Y.,Sun Yat Sen University | And 8 more authors.
Molecular Vision | Year: 2011

Purpose: The purpose of the current study was to investigate the effect of topical administration of KH906 on corneal neovascularization (NV). Methods: To induce corneal neovascularization, chemical cauterization of the corneas of the right eyes of forty-eight New Zealand white rabbits was performed by touching the central cornea with an 8-mm-diameter NaOH-soaked Whatman filter paper for 60 s. On the next day after modeling, the rabbits were randomly and equally divided into six groups: PBS control group, 0.1% dexamethasone group, 10 mg/ml Avastin group, 5 mg/ml KH906 group, 10 mg/ml KH906 group, and 20 mg/ml KH906 group. The rabbits in the six groups received topical administration of 50 μl of the different solutions on the cornea four times per day for 14 days. Corneal neovascularization was analyzed by slit-lamp biomicroscopy 10 and 14 days after chemical cauterization. Corneal fluorescein staining was performed to evaluate the extent of corneal epithelial defect on the 7th, 10th, and 14th days. The VEGF level of the cornea was evaluated by ELISA assay. Results: On the 10th and 14th days after chemical cauterization, the length of the longest new vessel and the areas of corneal neovascularization in all KH906-treated groups were significantly reduced compared to those of the PBS-treated group (p<0.05). The VEGF level of the cornea in all KH906-treated groups was significantly decreased compared to that of the PBS-treated group (p<0.05). Corneal fluorescein staining showed that KH906 had no effect on corneal epithelial healing. Conclusions: Topical administration of KH906 significantly inhibited alkali burn-induced corneal neovascularization in rabbits. The new eye drops of KH906 may have a broad application for human corneal neovascularization in the near future. © 2011 Molecular Vision.

Bai H.,Chengdu Kanghong Biotechnology Co. | Wen B.-X.,Chengdu Kanghong Biotechnology Co. | Zhu W.-L.,Chengdu Kanghong Biotechnology Co. | Ke X.,Chengdu Kanghong Biotechnology Co.
Chinese Journal of New Drugs | Year: 2016

Objective: To develop an ELISA method for assessing immunogenicity of conbercept in Rhesus monkey. Methods: An ELISA method was developed using conbercept and goat-anti-human HRP-IgG Kappa light chain as capture and detector protein, respectively. Validation of precision and specialization of the method were conducted then. To further characterize anti-conbercept antibodies, positive serum were analyzed by cell proliferation assay. Results: The best coating concentration was 5 μg·mL-1, and the optimal dilution ratio of the detected antibody was 1∶2 500. The cut point of screening was 0.162, and inter- and intra-batch coefficient variations were less than 15%. Conbercept concentration of 10 μg·mL-1 or less had no effect on detection. Anti-conbercept antibody was positively detected in 15 out of the 24 serum samples(62.5%). HUVEC cell proliferation assay indicated that all the positive serum can not neutralize conbercept. Conclusion: The method for analyzing anti-conbercept antibody is validated; it is valuable for pre-clinical and clinical applications. © 2016, Chinese Journal of New Drugs Co. Ltd. All right reserved.

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