Furthermore, we used the molecular fingerprint method to depict the specific characteristics of the novelty of the molecules generated by O 2 -GEN. As shown in Figure .d, the average fingerprint similarity between the most similar molecules in the original dataset is 0.93, while the similarity between the molecules we generated and the most similar molecule pairs in the original dataset is only 0.17. This indicates that our framework has the ability to generate novel large-scale OOMs in a broader chemical space.