John R. Inge Gaikoku-Jimu-Bengoshi Jimusho

(Sughrue, Mion, Zinn, Macpeak & Seas)

The USPTO on July 14, 1995 issued a final version of its guidelines and supporting legal analysis, initially proposed last December, to assist patent office personnel in their review of patent applications for compliance with the utility requirements of 35 USC §101 and §112, first paragraph.^{1 2}

Among other things, the guidelines clarify how the USPTO will interpret the "specific utility" requirement of §101.³ That is, an applicant must provide only one credible assertion of specific utility for any claimed invention to satisfy the utility requirement. Furthermore, an assertion of specific utility in the patent specification creates a presumption of utility.⁴ To overcome this presumption, the examiner must establish that it is more likely than not that one of ordinary skill would doubt (i.e., question) the truth of the statement of utility.

Thus, if the applicant asserts that the claimed invention is useful for any particular purpose (i.e., a specific utility), and that assertion would be considered credible by a person of ordinary skill, the examiner is not to impose a rejection based on lack of utility. Furthermore, if the invention has a well established utility, regardless of any assertion made by the applicant, the examiner is not to impose a rejection based on lack of utility.

On the other hand, if the utility asserted by the applicant is not credible (more particularly, if no assertion of specific utility for the claimed invention is credible), and the claimed invention does not have a well established utility, the examiner is to

(1) reject the claims under 35 USC §101 on the grounds that the invention as claimed lacks utility, and

(2) reject the claims under 35 USC §112, first paragraph, on the basis that the disclosure fails to teach how to use the invention as claimed.

More particularly, the burden is initially on the examiner to make a prima facie showing that the claimed invention lacks utility, and to provide a sufficient evidentiary basis for factual assumptions relied on in establishing the prima facie case.

If a proper rejection under 35 USC §101 has been made, the burden then shifts to the applicant to rebut the prima facie case. After a response is filed, the examiner must again review the complete record to determine whether to maintain the rejection. If the record as a whole would make it more likely than not that the asserted utility for the claimed invention would be considered credible by a person of ordinary skill, the rejection under 35 USC §101 should be removed.

With respect to biological inventions, the USPTO legal analysis emphasizes that evidence of pharmacological or other biological activity of a compound will be relevant to an asserted therapeutic use if there is a reasonable correlation between the activity in question and the asserted utility. Statistical certainty is not required. Also, there is not requirement for the applicant to provide evidence of success in treating humans even where such a utility is asserted.

The USPTO legal analysis also emphasizes that any combination of evidence from in vitro or in vivo testing can be sufficient to establish the credibility of an asserted utility. More particularly, if reasonably correlated to the particular therapeutic or pharmacological utility, data generated using in vitro assays, or from testing in an animal model or a combination thereof, should be sufficient to establish utility.

The USPTO legal analysis also emphasizes that evidence of structural similarity to known useful compounds should be given appropriate weight in determining whether one skilled in the art would find the asserted utility credible. Furthermore, while an applicant may be required to provide evidence to show that an invention will work as claimed, it is improper for an examiner to request evidence of safety in the treatment of humans or the degree of effectiveness when used to treat humans.

The decision of In re Brana concerns pharmaceutical inventions, and more particularly is concerned with correlation of the in vivo and in vitro activity of a claimed compound to its asserted therapeutic use in order to satisfy the practical utility requirement of 35 USC §101. Furthermore, the decision illustrates the initial burden that is placed on the examiner to make a prima facie showing to support a rejection for lack of utility. Many of the issues addressed in the In re Brana decision are also set forth in the USPTO utility guidelines.⁵

On June 30, 1988, Brana et al. filed a patent application directed to non-symmetrically substituted 5-nitrobenzo-isoquinoline-1, 3-dione compounds for use as antitumor substances.

The specification stated that non-symmetrical substitutions provide compounds with "a better action and a better action spectrum as antitumor substances" than known benzo-isoquinolines. More particularly, the specification compared the effectiveness of the claimed compounds with structurally similar symmetrically substituted compounds disclosed in the prior art (the Paull reference). ⁶

Furthermore, the specification illustrated the cytotoxicity of the claimed compounds against human tumor cells in vitro, and concluded that these tests "had a good action".

The examiner initially rejected the claims as obvious over U.S. Patent 4,614,820 to Zee-Cheng et al. This reference was cited as disclosing structurally similar symmetrically substituted compounds for use as antitumor agents.

In response, the applicants submitted declaration evidence showing that the claimed non-symmetrically substituted compounds were far more effective as antitumor agents than the symmetrically substituted compounds disclosed by Zee-Cheng et al. Furthermore, the applicants urged that even though the differences in structure were slight, there was no suggestion in the art that the improved results would have been expected.

The examiner withdrew the rejection over prior art, but finally rejected the claims on other grounds.

The claims were finally rejected under 35 USC §112, first paragraph. The basis for rejection was that the specification failed to describe any specific disease against which the claimed compounds were active. The examiner also concluded that the prior art tests performed by Paull (in vivo murine models) and the tests disclosed in the specification (activity against human tumor cells in vitro) were not sufficient to establish a reasonable expectation that the claimed compounds had a practical utility (i.e., antitumor activity in humans). The examiner further noted that a rejection also could have been made under 35 USC §101 for failure to disclose a practical utility.

During prosecution of the application, the applicants submitted a declaration under 37 C.F.R. §1.132 of Michael Kluge showing the antitumor activity of several compounds within the scope of the claims against a standard murine tumor model in vivo. Based thereon, Kluge concluded that these compounds would likely be clinically useful as anti-cancer agents.⁷

The applicants appealed the final rejection to the Board of Appeals.

The Board affirmed the rejection in a decision dated March 19, 1993. The bases for the Board's decision were as follows:

1. The applicants' specification failed to disclose a specific disease against which the claimed compounds are useful, and therefore, absent undue experimentation, one of ordinary skill in the art was precluded from using the invention.

2. Even if the specification did allege a specific use, the applicants failed to prove that the claimed compounds are useful. More particularly, the Board found that the tests offered by the applicants to prove utility were inadequate to convince one of ordinary skill in the art that the claimed compounds are useful as antitumor substances.

The applicants then appealed the decision of the Board to the Court of Appeals for the Federal Circuit.

F. DECISION OF THE FEDERAL CIRCUIT⁸

The court found that the applicants' favorable comparison (in the specification) to Paull's symmetrically substituted compounds implicitly asserts that the claimed compounds are highly effective (i.e., useful) against lymphocytic leukemia.⁹ Based thereon, the court held that in light of the explicit reference to Paull, the specification does allege a sufficiently specific use.¹⁰

The court pointed out that the initial burden is on the PTO to make a prima facie showing that the claimed invention lacks utility.

The PTO has the initial burden of challenging the applicants' presumptively correct assertion of utility in the disclosure of the specification. Only after the PTO provides evidence showing that one of ordinary skill in the art would reasonably doubt the asserted utility does the burden shift to the applicant to provide rebuttal evidence sufficient to convince such a person of the invention's asserted utility.

The court found that the PTO failed to meet its initial burden. Namely, the court found that the references cited by the examiner in support of the rejection did not question the usefulness of any compound as an antitumor agent or provide any other evidence to cause one of ordinary skill in the art to question the asserted utility of the applicants' compounds.¹¹

The court also noted that the purpose of treating cancer with chemical compounds does not suggest an inherently unbelievable undertaking.

Taking these facts into consideration (the nature of the invention and the PTO's proffered evidence), the court concluded that one skilled in the art would be without basis to reasonably doubt the applicants' asserted utility on its face. Furthermore, the court held that the PTO did not satisfy its initial burden and that the applicants should not have been required to substantiate their presumptively correct disclosure to avoid a rejection under 35 USC §112, first paragraph.

The court furthermore found that even if the PTO had met its initial burden thereby shifting the burden to the applicants to offer rebuttal evidence (i.e., even if one skilled in the art would have reasonably questioned the asserted utility), the applicants submitted sufficient evidence to convince one of ordinary skill in the art of the asserted utility.

Namely, the court was of the opinion that the in vivo test results presented in the Kluge declaration (showing that several compounds within the scope of the claims exhibited significant antitumor activity in a standard murine tumor model) alone would have been sufficient to rebut a prima facie case of lack of utility.

Furthermore, the court was also of the opinion that the prior art (which disclosed structurally similar compounds proven to be effective as chemotherapeutic agents in vivo against various tumor models) further supported the conclusion that one skilled in the art would be convinced of the applicants' asserted utility.

The Commissioner took the position that such in vivo tests in animals are only preclinical tests to determine whether a compound is suitable for testing in humans, and that these tests are not reasonably predictive of the success of the claimed compounds for treating cancer in humans.

However, the court admonished the Commissioner not to confuse the requirements for obtaining government approval to market a drug (testing for safety and effectiveness) with the requirements for obtaining a patent. In this regard, the court noted as follows:

Additionally, the court noted that its predecessor court (the CCPA) had long ago determined that proof of an alleged pharmaceutical property for a compound by statistically significant tests with standard laboratory animals is sufficient to establish utility. Namely, one who has taught the public that a compound exhibits some desirable pharmaceutical property in a standard laboratory animal has made a significant and useful contribution to the art, even though it may eventually appear that the compound is without value in the treatment of humans.¹²

Moreover, the court took notice that NCI is of the opinion that the tests are statistically significant because the NCI has explicitly recognized the subject murine tumor models as standard screening tests for determining whether new compounds may be useful as antitumor agents.

For all of the above reasons, the court concluded that the applicants' disclosure complied with the requirements of 35 USC §112, first paragraph, and reversed the Board's decision.

The USPTO guidelines, in general, are consistent with the holding of the court in re Brana. The guidelines clarify what should have been the examining standards on utility. However, more often than not, these standards were not followed by examiners.

The USPTO guidelines and their implementation, including internal controls and uniform training, should be quite beneficial to applicants. However, the effectiveness of the guidelines will depend on how examiners (and the Board) handle the guidelines, and the type of quality control standards that the USPTO may implement.

1) 60 Fed. Reg. 36263 (1995); 50 Pat. Trademark & Copyright J. (BNA) No. 1237, at 295 (July 20, 1995).

2) The requirement that an invention have utility is found in 35 USC §101: "Whoever invents ... any new and useful ... composition of matter ... may obtain a patent therefor..." (emphasis added). It is also implicit in 35 USC §112, first paragraph, which reads: "The specification shall contain a written description of the invention, and of the manner and process of making and using it ... to enable any person skilled in the art ... to make and use the same ... " (emphasis added). The specification cannot enable use of an invention if the claimed invention does not have utility.

3) The utility requirement means that the claimed invention must have a specific "usefulness" with "real world" value.

4) A specification disclosure which contains a teaching of the manner and process of making and using the invention in terms which correspond in scope to those used in describing and defining the subject matter sought to be patented must be taken as in compliance with the enabling requirement of the first paragraph of §112 unless there is reason to doubt the objective truth of the statements contained therein which must be relied on for enabling support. In re Brana, 34 USPQ2d at 1441 (Fed. Cir. 1995). In re Langer, 183 USPQ 288 (CCPA 1974).

5) In re Brana is repeatedly cited in the USPTO legal analysis.

7) The specification must be enabling as of the filing date of the application. Although submitted after the filing date, the Kluge declaration could be used to substantiate any doubts as to the asserted utility because this pertains to the accuracy of a statement already in the specification. Namely, the declaration was submitted to prove that the disclosure was enabling when filed.

8) The case was heard before circuit judges Plager, Lourie and Rader and decided on March 30, 1995. The decision is reported at 34 USPQ2d 1437 (Fed. Cir. 1995).

9) However, in the absence of such a comparison, the court noted that the applicants' general assertion of "antitumor activity" would not have been a sufficient disclosure of specific utility. In the decision of In re Kirk, 153 USPQ 48 (CCPA 1967), the applicants claimed a new class of steroid compounds. One of the alleged utilities disclosed in the specification was that the compounds possessed "high biological activity". The specification, however, failed to disclose which biological properties made the compounds useful. For these reasons (and others), the court concluded that the alleged use was too obscure to enable one skilled in the art to use the claimed invention.

10) The court disagreed with the Commissioner's position that the reference to Paull did not provide a specific disease against which the claimed compounds can be used. More particularly, the Commissioner argued that the murine tumor models employed by Paull were not diseases because the only way that an animal could get sick is by direct injection of the cell line. In this regard, the court noted that the subject cell lines were originally derived from lymphocytic leukemias in mice, and that it would be unreasonable to require the applicants to wait until an animal naturally developed this specific tumor before testing the effectiveness of a compound.

11) More particularly, the court characterized these references as discussing the therapeutic predictive value of in vivo murine tests. This reference would be relevant only if the applicants had to prove the value of the asserted utility in humans.

12) In re Krimmel, 130 USPQ 215 (CCPA 1961).