What is not clear is whether these modifications are an over optimization over "the original". For each patient the cost/benefit calculation will be different and based on many variables.

I'm not an expert and I can't comment on specifics. But I'm of the opinion that a small enhancement is not the same as an invention of a drug and it doesn't come anywhere close to extending the life of the patent - unless that tiny change actually makes a big different in effectiveness.

Any good patent system should find a good balance between the two seemingly conflicting goals of incentivizing companies to innovate and keeping the price down for patients.

"[The authors] describe the history of insulin as an example of “evergreening,” in which pharmaceutical companies make a series of improvements to important medications that extend their patents for many decades. This keeps older versions off the generic market, the authors say, because generic manufacturers have less incentive to make a version of insulin that doctors perceived as obsolete. Newer versions are somewhat better for patients who can afford them, say the authors, but those who can’t suffer painful, costly complications."

This isn't really a story about patents, it's about marketing and a chicken-and-egg problem. You could buy dirt cheap generic insulin if anyone made it, but they don't, because nobody wants to buy it, probably because nobody makes it.

[1]: http://www.hopkinsmedicine.org/news/media/releases/why_peopl...