Objective: To screen monoclonal antibody against protein drugs bound with plasma protein in blood samples. Methods: After coated with rabbit anti-K102 polyclonal antibody purified by affinity chromatography adding K102 antigen diluted with PBS containing 10% monkey plasma PBS and the supernatant of hybridoma and HRP-goat anti-mouse IgG are added to screen positive hybridoma lines which might produce monoclonal antibodies. Results: In use of the method of double-antibody sandwich ELISA screening, the six hybridoma lines are successfully screened to be capable of screening stably the antibody against K102, named as 1C9, 2D7, 3E2, 5F4, 5F6, 6B9. The monoclonal antibodies could detect K102 concentration in the blood samples. Conclusion: The improved double-antibody sandwich ELISA can be used to screening hybridoma cell lines of monoclonal antibodies against biodrugs bound with plasma protein.