The decision in In re Albrecht results from an appeal from the USPTO to the CCPA where the applicants’ eight claims directed to bis-esters and bis-amides of carbazoles were rejected. Claim 1 of the invention, directed to a Markush genus of compounds is reproduced in its entirety from the opinion and shown in Figure below.The additional rejected claims, 2–8, were directed to additional, presumably narrower embodiments of claim 1. In rejecting claims 1–8 for alleged obviousness, the USPTO examiner (and majority of the USPTO Board that upheld the rejection) relied on a single piece of prior art from the chemical literature. The cited art related to a study of the local anesthetic properties of certain carbazoles, dibenzofurans, and dibenzothiophene derivatives. There were no bis-basic esters of carbazoles disclosed (only mono-basic esters), but there was one bis-basic ester of a dibenzofuran that was disclosed, having the structure shown in Figure below.
The bis-basic ester of the dibenzofuran from the cited art is structurally similar to the Markush genus disclosed in Albrecht’s application but does not fall within it since the core structure is a dibenzofuran and that of Albrecht is a carbazole. This

bis-basic ester of a dibenzofuran

Figure : Claim 1 from In re Albrecht.

Claim 1 from In re Albrecht.

Figure :Prior art dibenzofuran.

is an important point because if the core structure of the prior art example shown in Figure above was a carbazole instead of a dibenzofuran, the compound would fall within
Albrecht’s genus and thus would have anticipated the genus, and it would have been game over for Albrecht, at least for the compounds of claim 1.28
In rejecting claims 1–8 of Albrecht’s application, the examiner noted that certain mono-basic esters of carbazole were reported to have “powerful” local anesthetic activity, whereas the corresponding dibenzofuran compounds were less effective. The further disclosure of the bis-basic dibenzofuran as having some minimal anestheticactivity was sufficient, the examiner alleged, to motivate a PHOSITA to make the bisbasicesters of the carbazole compounds like those claimed in Albrecht’s application,since the prediction would be that the bis-basic ester of the carbazole would be a more effective anesthetic than the disclosed bis-basic dibenzofuran. It would, therefore, be obvious to make these compounds, and the claims should be rejected.

The applicant appealed and in its opinion, the CCPA note the cited reference also indicated that the disclosed compounds were highly irritating to the skin and could not be considered as useful for anesthetic purposes. Due to this feature, the court found that one of ordinary skill in the art would not have been motivated to modify the prior art compounds because those prior art structures did not have an overall interesting activity. So despite the structural similarities of the compounds of claims1–8 of the Albrecht et al. application and those of the prior art reference, the CCPA reversed the USPTO’s rejection. In driving home its logic for reversal, the CCPA quoted from its own earlier decision:
How can there be obviousness of structure, or particularly of the subject matter as a whole, when no apparent purpose or result is to be achieved, no reason or motivation to be satisfied, upon modifying the reference compounds structure? Where the priorart reference neither discloses nor suggests a utility for certain described compounds,why should it be said that a reference makes obvious to one of ordinary skill in the art an isomer, homolog or analog of related structure, when that mythical, but intensely practical, person knows of no “practical” reason to make the reference compounds, much less any structurally related compounds?
The compounds from the prior art reference cited against the Albrecht application possessed utility in that they were active as local anesthetics, but they lacked overall utility in that their irritant qualities would exceed their usefulness as local anesthetics.It appeared to the CCPA that a chemist of skill in the art, reading the cited reference for all that it disclosed, would not have been motivated to make additional close analogues based on the likelihood that they too would be irritants and thus have no practical utility.
What if the prior art would motivate one of ordinary skill in the art to make the applicant’s claimed invention but for a different reason than that relied on by the applicant? Should it matter? The following example, taken from a CAFC opinion decided this exact question. The named petitioner, Dillon, was an assignor of the invention to Union Oil Company, whose application for patent was rejected in the USPTO. After unsuccessfully appealing to the USPTO Board of Appeals, the petitioner appealed to the CAFC and the rejection of the patent ability of the claims was affirmed. The subject matter of the relevant claims was directed to compositions containing tetra-orthoesters in hydrocarbon fuels and methods of reducing particulate emissions using those tetra-orthoesters in hydrocarbon fuel. To clarify the subject

Prior art dibenzofuran.

FIGURE :Claimed tetra-orthoester from Dillon.

matter of the dispute, the broadest claim from the patent application is shown in Figure above

As a preliminary matter, the CAFC noted that the tetra-orthoesters were a known class of compounds but that their combination with a hydrocarbon fuel was undisputedly novel and therefore, that their use to reduce particulate emissions from combustion of hydrocarbon fuel was not shown or suggested in the prior art. Nevertheless,the CAFC found the claims obvious based upon the combined teachings of several U.S. patents. One patent (U.S. 4,395,267) described hydrocarbon fuels containing various additives for de watering, including tri-orthoesters, and another patent (U.S. 4,395,267) described tri-orthoesters for use in hydrocarbon fuel to prevent phase separation between a hydrocarbon fuel and alcohol.33 The CAFC also listed some U.S. patents as secondary references that disclosed both tri- and tetraorthoesters for use as water scavengers in hydraulic (non hydrocarbon) fluids. The CAFC held that one of ordinary skill in the art would have been motivated to addtetra-orthoesters to a hydrocarbon fuel to remove water and, moreover, that there was reasonable expectation that such a compound would reduce water in the fuel sincetri- and tetra-orthoesters had been shown to work in other fluids (brake fluids), thus establishing equivalent activity between tri- and tetra-orthoesters for purposes of water removal. Furthermore, there was a sufficiently close structural relationship between the two compounds to expect at least similar results for reduction of articulate emissions.
Although the CAFC had already acknowledged that there was nothing in the art to specifically suggest that a tetra-orthoester in fuel would act to reduce particulate composition, the court found that there was sufficient motivation in the prior art to make a hydrocarbon fuel composition that contained a tetra-orthoester since the priorart already disclosed a tri-orthoester in fuel as a water-reducing agent and the priorart also disclosed that a tetra-orthoester would be predicted to behave the same way.In so finding, the CAFC introduced the broader principle that to make a prima facie case of obviousness, it is not necessary that the claimed compound will be expected by one of ordinary skill in the art to have the same or even a similar utility as the utility disclosed by the applicant; it just needs to have sufficient overall utility to motivate one to make and try structurally similar compounds.
One way of thinking about this finding is to appreciate that the Dillon application claims a composition, not a reason for making that composition. If all of the limitations of that claim are suggested or taught in the prior art, then that claim is non patentable.According to the court’s reasoning, it does not matter why one of skill in the art would have been motivated to make Dillon’s composition, only that they would have been motivated.
In the context of ANDA litigation on pharmaceutical compound claims, a company challenging the innovator’s patent will often allege that the claimed compound is obvious in view of one or more similar structures that have been disclosed in the prior art. The case of Yamanouchi Pharmaceutical Co., Ltd. v. Danbury Pharmacal,Inc. is representative of the federal courts’ handling of compound composition claims covering novel drug substances that are at least somewhat similar to prior art structures. H2-receptor antagonists work to prevent acid indigestion by inhibiting histamine action on H2-receptors on the basolateral membrane of parietal cells in the stomach. Yamanouchi was the assignee of a patent (U.S. 4,283,408) that claimed,inter alia, the structure of the H2-receptor antagonist famotidine (sold in the United States as Pepcid_R ). In January 1997, the generic drug manufacturers Danbury (a division of Sche in) and Marsam (herein after collectively referred to as Danbury) filed an ANDA with the FDA, seeking approval to bring generic famotidine to market. In their certification to the FDA, the generic defendants alleged that claim4 (specifically covering famotidine) of the patent was invalid (Figure above).Yamanouchi filed suit against Danbury for infringement, and the case was heard in the Federal District Court of the Southern District of New York, where Yamanouchip revailed. Danbury appealed to the CAFC, still alleging that claim4of U.S. 4,283,408was obvious in view of a combination of references. In its assertions, Danbury cited

Claimed tetra-orthoester from Dillon.

FIGURE :Claim to genus and species covering famotidine.

a compound from a prior art patent awarded to Yamanouchi (example 44 in U.S.4,252,819) and the prior art H2-antagonist tiotidine (both structures are compared to famotidine in Figure above=).

Claim to genus and species covering famotidine.

FIGURE :Structures of famotidine and prior art.

Structures of famotidine and prior art.

FIGURE :Danbury’s obviousness argument.

and then make a bioisosteric substitution of the carbamoyl (CONH2) group in the intermediate compound with a sulfamoyl group (SO2NH2) (see Figure above).In its affirmation of the District Court’s holding that rejected Danbury’s obviousness argument, the CAFC asserted that Danbury failed to provide motivation for selecting compound example 44 to pursue as a lead. The court pointed out that there were more potent compounds than example 44 known in the art, and thus contrary to Danbury’s assertion, the simple potency of example 44 was not motivation enough to select it for further modification. Beyond this, Danbury failed to explain what would have motivated one to use the polar tail from compound example 44 in combination with the heterocycle of tiotidine and then substitute the carbamoyl group with the sulfamoyl group. If Yamanouchi had not performed all of these steps, the end result would not have been nearly so successful. For example, if the sulfamoyl group had been substituted for the carbamoyl group on example 44 without substituting the heterocyclering of tiotidine, then the resulting compound would have had approximately1/4000 the potency of famotidine.The CAFC also commented on the absence of a reasonable expectation of success.
In this particular instant, the CAFC rejected Danbury’s reasoning that an expectation of success merely required an expectation of minimal activity. Rather, the CAFC held that the success of discovering famotidine was not the expectation of discovering one of the “tens of thousands of compounds that exhibit baseline H2 antagonist activity”but “was the finding of a compound that had high activity, few side effects, and lacked toxicity.”

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