Special problems can arise in chemical cases where a question often arises as to whether a compound having a minor difference in structure to a prior compound is obvious. The leading case ( In re Papesch )[171] held that in such cases, if the new compound possesses properties that are surprising and unexpected then the mere fact that the change in structure is a minor one does not render the new compound obvious. In determining questions of obviousness, one must consider the compound as a whole, and that includes both its structure and its properties.

In the case of In re Dillon ,[172] the Court of Appeals of the Federal Circuit with 12 judges sitting en banc reversed a previous decision of a panel of three of its members to effect what may be a significant change in the tests of obviousness applied to patent claims directed to novel chemical compounds and compositions.

In its en banc decision, the Federal Circuit decided that structural similarity was sufficient for finding of prima facie obviousness in respect of a claim for a new compound or composition if there is something in the prior art that gives reasons or motivation to make that new compound or composition, even if these are totally unrelated to its newly discovered surprising properties. The Court indicated that the evidence of surprising properties could still be used to rebut the presumption of obviousness rising from the structural similarity commenting:

The Court was, however, emphatic that in order to establish prima facie obviousness it was not necessary that there should be a suggestion in the prior art "[t]hat the claimed compound or composition will have the same utility as one newly discovered by the applicant." Additionally it is important to note that when referring to unexpected improved properties the court required that these were “properties that the prior art does not have” not simply properties that the prior art was not known to have. That is where the structural similarity is close and one wishes to rely on the properties of a new compound to overcome an obviousness argument, there must be some actual difference in the properties of the new compound from the prior art and not merely some newly discovered property that is common to both of them before one can obtain compound per se protection for the new compound.

In the area of biotechnology the degree of unpredictability resulting from the degeneracy of the genetic code has led to decisions holding that knowing "the amino acid sequence of a protein does not necessarily render particular DNA molecules encoding the protein obvious.” [173]