There is a so-called "meta" team that is optimized to fight Osh, built around Isaac. The team is chosen such that they enhance each other's capabilities and can cause a lot of damage when levelled up.

Here is the team composition:

Isaac (pet: Oliver)

Jhu (pet: Fenris)

Nebula (pet: Cain)

Sebastian (pet: Albus)

Martha (pet: Axel)

Team Pet: Albus (until about level 160 where you may need Axel in order to stay alive until the end).

NOTE: Do NOT, under any circumstances, increase Isaac's Magic Defense glyph and do not get/upgrade his Magic Defense skin, this will get in the way of his ult which you need to fight Osh.