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Isn't it the same like any other one? Usualy you have GND=0V and let say VDD=5V in your case GND=-3V and VDD=1V
SO the refernece node is still the same on die. Just different potential
Depends on available characterized protection structures. If floating (in N-well) zener diodes with BV=5...8V are available then back-to-back diodes can be used. Mirrored SCR can also be used to provide bipolar protection.
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