You may think of the typing library as a specification on how to declare certain types. If something is not defined in that specification then it’s always better assume it to be an undefined behavior.
However in the particular case of Python and typing we have a kind-of-reference static type checker which is mypy. So in order to get an answer for your question, or just programmatically check types, we may use it and see if it shows any warnings.
Here’s an example:
$ cat check_optional.py
import typing
def fn(x: typing.Optional[int, str]):
pass
$ mypy check_optional.py
check_optional.py:3: error: Optional[...] must have exactly one type argument
So no, Optional[T, U] is not possible in terms of mypy even if there’s no trouble declaring it within the typing library.
Besides from “functional programming” perspective both Optional and Union are two distinct but well-known and well defined monads. A combination of two monads (Union[T, U, None]) is another monad, which however behaves differently than Optional and thus should not be named so. In other words, Union[T, U, None] is isomorphic to (=same as) Optional[Union[T, U]], but not to a general Optional[X].