Court Opinion

ID: 9475352
Source: CourtListenerOpinion
Date Created: 2023-08-05 05:24:28.79485+00
Date Added: 2024-06-11T17:44:39.655987
License: Public Domain

BALDWIN, Circuit Judge,
dissenting.
The rejection by the board is flawed because it did not analyze the invention according to the requirement of 35 U.S.C. § 103. The board wrote:
The issue before us in considering the instant claims on their merits for patent-ability is whether the artisan having the requisite skill in the pertinent art area and a knowledge of the available prior art would have been motivated to employ amitriptyline in the treatment of human depression.
That is, whether it would have been obvious to try amitriptyline as an antidepressant. Guided by the disclosure of the applicant, the board pieced together information from various patents, journal articles, and papers, and concluded:
It remains our position that one having ordinary skill in this art are[sic] would have been familiar with the concept of bioisosterism and because of this knowledge would have concluded that the known compound, i.e., amitriptyline, would be potentially useful as an antidepressant. [Emphasis ours.]
That is, it would have been obvious to try amitriptyline as an antidepressant. Obvious-to-try is not the test for patentability under 35 U.S.Q. § 103. This court and its predecessor, the CCPA, have repeatedly rejected that approach. In re Goodwin, 576 F.2d 375, 377, 198 USPQ 1, 3 (CCPA 1978); In re Antonie, 559 F.2d 618, 620, 195 USPQ 6, 8 (CCPA 1977); In re Lindell, 385 F.2d 453, 455, 155 USPQ 521, 523 (CCPA 1967); In re Tomlinson, 363 F.2d 928, 150 USPQ 623 (CCPA 1966); In re Papesch, 315 F.2d 381, 137 USPQ 43 (CCPA 1963); see also In re Grabiak, 769 F.2d 729, 226 USPQ 870 (Fed.Cir.1985).
Congress has also rejected that approach by enacting the second sentence of 35 U.S.C. § 103, which states “[patentability shall not be negatived by the manner in *1100which the invention was made.” The reviser’s note on this sentence states “it is immaterial whether it resulted from long toil and experimentation or from a flash of genius.”
The obvious-to-try analysis is an attack on the method of making an invention that specifically penalizes people in areas of endeavor where advances are won only by great effort and expense. The pharmaceutical field is particularly hard hit because there is an overabundance of structures that are obvious to try. Consider, for example, the Petersen reference which the majority cites to demonstrate the possibility that a nitrogen atom may be replaced by a double-bonded carbon atom. This journal article records an attempt to find drugs useful for the treatment of endogenous psychoses, i.e., tranquilizers. The researchers tested eighteen chemicals with closely related structures. These materials were injected into mice, and compared for their ability to make the mice fall asleep. The results of these tests may be tantalizing and useful, but only as a guide for further research. I agree that, based on this information and the other references cited by the board, the researcher with ordinary skill in the art would be motivated to investigate the possibility of substituting a double-bonded carbon atom for nitrogen. The researcher would also be motivated to test every other structural variation in Petersen, as well as a host of others. Under an obvious-to-try analysis, any of these structures which ultimately is shown to be effective as an antidepressant in human beings would be unpatentable because the researcher dared to follow a logical plan.
The board and the majority also err by reading too much certainty into the teachings of the references. They have not considered the references as a whole. Friedman discusses the phenomenon that compounds with similar chemical structures sometimes behave in a similar fashion in a biological system. Once such a compound has been tested and found to have the same biological activity, it is called “bio-isosteric.” 1
Friedman also teaches that an isosteric compound “may have the same activity as the original, or more usually it may have an antagonistic effect.” (Emphasis added.) Friedman explains that in order to predict biological activity with accuracy, one ideally should know (1) the mechanism by which the original drug acts and (2) what part of the structure of the original drug is critical to the original drug activity.2 That reference also unequivocally states that comparisons should be made in living systems, but such information is not easily available. That reference relies on in vitro testing, and it specifically states that in vitro results may or may not correlate with clinical studies. It also clearly states that, for the purposes of its discussion, biological activities such as absorption, distribution, conjugation (detoxification), taste, odor and side effects of drugs will be ignored. Friedman concludes that compounds with similar structures need not be bio-isosteric.
The Burger reference does discuss bio-isosterism and its usefulness in designing new drugs. Its evaluation of bio-isosterism as a tool for predicting drug activity is as follows:
However, if one can achieve a gradual change of biological behavior and follow it accurately at each step of minor structural alteration, one is bound to enhance one property, suppress another, and ultimately arrive at a drug suitable for therapy. Shortcuts to this disconcertingly tedious process have not been found, and this is probably responsible for the still *1101prevailing opinion that new useful drugs will be discovered most easily by more or less empirical procedures,
at page 369, and
Slight stereochemical or structural changes may alter considerably the biological role of a compound. Patient variation of at least a reasonable number of structures is still the only answer to this question,
at page 370.
The Roche reports contain background information about various pharmacological effects of amitriptyline. The information was derived from testing for its toxicity and tranquilizing effect on animals. This information would be essential to a decision to clinically test the drug. It is not sufficient to show the drug would be useful for treating human beings. Congress gave pragmatic recognition to the difficulty of determining whether a new drug is useful by its enactment of the 1962 amendment to 21 U.S.C. § 321. That action was taken in response to problems caused by another tranquilizer, thalidomide.
Neither these references, nor the other references cited by the board and the majority purport to teach the worker with ordinary skill in the art that amitriptyline is a drug that is useful for treating depression in human beings. That conclusion is steps removed from the information presented by these sources. I would reverse.

. The term “bio-isosteric" therefore is simply a conclusion drawn after testing. The label is properly limited to the system and purpose for which the compounds were tested. For example, two drugs could be bio-isosteric with respect to making mice fall asleep, and not bio-isosteric when tested at a particular dosage level for the treatment of high blood pressure in human beings. The theory of bio-isosterism as used by the board and majority is nothing more or less than an analysis of structural obviousness.

. Neither this reference nor any of the others purport to disclose either piece of information.