A sick cat is vulnerable to predators. Since cats live in colonies is the wild, attracting a predator to their colony is not a good thing. So the healthy cats will often gang up on the sick one so it leaves the colony to go die elsewhere, or in some cases kill it themselves.
There isn't any way to really stop it, the Feliway may help, you could try putting the aggressor on medication to chill him out. But of that doesn't work, the only real way to deal with it is to separate them.
Why do I know all this? I had the problem with Kobi when Callie had IBD/lymphoma. They were separated when I wasn't home to supervise for the last 6 months of Callie's life and then completely separated for the last 3 months. I played musical rooms with cats several times a day. I did this on the advice of a friend who is in charge of the medical treatment at the local shelter. She warned me that since Kobi was 18+ pounds and Callie was 7 pounds and still losing, that he could very well kill her.
I also want to add that the OP's issue could be a case of re-directed aggression. If the male cat and the female he's picking on were together when an issue arose with a cat outside, he could be reacting to that and not picking on the other cat because she may not have been around when the incident occurred. So if there are stray cats hanging around outside the house, that could be another possibility. If that's the case, separating them and going through a formal re-introduction process may be needed.
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Holly, Misty & their friend, Jake, the dog.
Onyx, Callie May, Maggie & Kobi forever in my heart.
Yes, I know I need a new signature pic...someday...