2107.03 Special Considerations for Asserted Therapeutic or Pharmacological Utilities [R-08.2012]
The federal courts have consistently reversed rejections by the Office asserting a lack of utility for inventions claiming a pharmacological or therapeutic utility where an applicant has provided evidence that reasonably supports such a utility. In view of this, Office personnel should be particularly careful in their review of evidence provided in support of an asserted therapeutic or pharmacological utility.
I. A REASONABLE CORRELATION BETWEEN THE EVIDENCE AND THE ASSERTED UTILITY IS SUFFICIENT
As a general matter, 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. Crossv. Iizuka, 753 F.2d 1040, 224 USPQ 739 (Fed. Cir. 1985); In re Jolles, 628 F.2d 1322, 206 USPQ 885 (CCPA 1980); Nelsonv.Bowler, 626 F.2d 853, 206 USPQ 881 (CCPA 1980). An applicant can establish this reasonable correlation by relying on statistically relevant data documenting the activity of a compound or composition, arguments or reasoning, documentary evidence (e.g., articles in scientific journals), or any combination thereof. The applicant does not have to prove that a correlation exists between a particular activity and an asserted therapeutic use of a compound as a matter of statistical certainty, nor does he or she have to provide actual evidence of success in treating humans where such a utility is asserted. Instead, as the courts have repeatedly held, all that is required is a reasonable correlation between the activity and the asserted use. Nelsonv.Bowler, 626 F.2d 853, 857, 206 USPQ 881, 884 (CCPA 1980).
II. STRUCTURAL SIMILARITY TO COMPOUNDS WITH ESTABLISHED UTILITY
Courts have routinely found evidence of structural similarity to a compound known to have a particular therapeutic or pharmacological utility as being supportive of an assertion of therapeutic utility for a new compound. In In re Jolles, 628 F.2d 1322, 206 USPQ 885 (CCPA 1980), the claimed compounds were found to have utility based on a finding of a close structural relationship to daunorubicin and doxorubicin and shared pharmacological activity with those compounds, both of which were known to be useful in cancer chemotherapy. The evidence of close structural similarity with the known compounds was presented in conjunction with evidence demonstrating substantial activity of the claimed compounds in animals customarily employed for screening anticancer agents. Such evidence should be given appropriate weight in determining whether one skilled in the art would find the asserted utility credible. Office personnel should evaluate not only the existence of the structural relationship, but also the reasoning used by the applicant or a declarant to explain why that structural similarity is believed to be relevant to the applicant’s assertion of utility.
III. DATA FROM IN VITRO OR ANIMAL TESTING IS GENERALLY SUFFICIENT TO SUPPORT THERAPEUTIC UTILITY
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 almost invariably will be sufficient to establish therapeutic or pharmacological utility for a compound, composition or process. A cursory review of cases involving therapeutic inventions where 35 U.S.C. 101 was the dispositive issue illustrates the fact that the federal courts are not particularly receptive to rejections under 35 U.S.C. 101 based on inoperability. Most striking is the fact that in those cases where an applicant supplied a reasonable evidentiary showing supporting an asserted therapeutic utility, almost uniformly the 35 U.S.C. 101-based rejection was reversed. See, e.g., In re Brana, 51 F.3d 1560, 34 USPQ 1436 (Fed. Cir. 1995); Crossv. Iizuka, 753 F.2d 1040, 224 USPQ 739 (Fed. Cir. 1985); In re Jolles, 628 F.2d 1322, 206 USPQ 885 (CCPA 1980); Nelsonv.Bowler, 626 F.2d 853, 856, 206 USPQ 881, 883 (CCPA 1980); In re Malachowski, 530 F.2d 1402, 189 USPQ 432 (CCPA 1976); In re Gaubert, 530 F.2d 1402, 189 USPQ 432 (CCPA 1975); In re Gazave, 379 F.2d 973, 154 USPQ 92 (CCPA 1967); In re Hartop, 311 F.2d 249, 135 USPQ 419 (CCPA 1962); In re Krimmel, 292 F.2d 948, 130 USPQ 215 (CCPA 1961). Only in those cases where the applicant was unable to come forward with any relevant evidence to rebut a finding by the Office that the claimed invention was inoperative was a 35 U.S.C. 101 rejection affirmed by the court. In re Citron, 325 F.2d 248, 253, 139 USPQ 516, 520 (CCPA 1963) (therapeutic utility for an uncharacterized biological extract not supported or scientifically credible); In re Buting, 418 F.2d 540, 543, 163 USPQ 689, 690 (CCPA 1969) (record did not establish a credible basis for the assertion that the single class of compounds in question would be useful in treating disparate types of cancers); In re Novak, 306 F.2d 924, 134 USPQ 335 (CCPA 1962) (claimed compounds did not have capacity to effect physiological activity upon which utility claim based). Contrast, however, In re Buting to In re Gardner, 475 F.2d 1389, 177 USPQ 396 (CCPA 1973), reh’g denied, 480 F.2d 879 (CCPA 1973), in which the court held that utility for a genus was found to be supported through a showing of utility for one species. In no case has a federal court required an applicant to support an asserted utility with data from human clinical trials.
If an applicant provides data, whether from in vitro assays or animal tests or both, to support an asserted utility, and an explanation of why that data supports the asserted utility, the Office will determine if the data and the explanation would be viewed by one skilled in the art as being reasonably predictive of the asserted utility. See, e.g., Ex parte Maas, 9 USPQ2d 1746 (Bd. Pat. App. & Inter. 1987); Ex parte Balzarini, 21 USPQ2d 1892 (Bd. Pat. App. & Inter. 1991). Office personnel must be careful to evaluate all factors that might influence the conclusions of a person of ordinary skill in the art as to this question, including the test parameters, choice of animal, relationship of the activity to the particular disorder to be treated, characteristics of the compound or composition, relative significance of the data provided and, most importantly, the explanation offered by the applicant as to why the information provided is believed to support the asserted utility. If the data supplied is consistent with the asserted utility, the Office cannot maintain a rejection under 35 U.S.C. 101.
Evidence does not have to be in the form of data from an art-recognized animal model for the particular disease or disease condition to which the asserted utility relates. Data from any test that the applicant reasonably correlates to the asserted utility should be evaluated substantively. Thus, an applicant may provide data generated using a particular animal model with an appropriate explanation as to why that data supports the asserted utility. The absence of a certification that the test in question is an industry-accepted model is not dispositive of whether data from an animal model is in fact relevant to the asserted utility. Thus, if one skilled in the art would accept the animal tests as being reasonably predictive of utility in humans, evidence from those tests should be considered sufficient to support the credibility of the asserted utility. In re Hartop, 311 F.2d 249, 135 USPQ 419 (CCPA 1962); In re Krimmel, 292 F.2d 948, 953, 130 USPQ 215, 219 (CCPA 1961); Ex parte Krepelka, 231 USPQ 746 (Bd. Pat. App. & Inter. 1986). Office personnel should be careful not to find evidence unpersuasive simply because no animal model for the human disease condition had been established prior to the filing of the application. See In re Chilowsky, 229 F.2d 457, 461, 108 USPQ 321, 325 (CCPA 1956) (“The mere fact that something has not previously been done clearly is not, in itself, a sufficient basis for rejecting all applications purporting to disclose how to do it.”); In re Wooddy, 331 F.2d 636, 639, 141 USPQ 518, 520 (CCPA 1964) (“It appears that no one on earth is certain as of the present whether the process claimed will operate in the manner claimed. Yet absolute certainty is not required by the law. The mere fact that something has not previously been done clearly is not, in itself, a sufficient basis for rejecting all applications purporting to disclose how to do it.”).
IV. HUMAN CLINICAL DATA
Office personnel should not impose on applicants the unnecessary burden of providing evidence from human clinical trials. There is no decisional law that requires an applicant to provide data from human clinical trials to establish utility for an invention related to treatment of human disorders (see In re Isaacs, 347 F.2d 889, 146 USPQ 193 (CCPA 1963); In re Langer, 503 F.2d 1380, 183 USPQ 288 (CCPA 1974)), even with respect to situations where no art-recognized animal models existed for the human disease encompassed by the claims. Ex parte Balzarini, 21 USPQ2d 1892 (Bd. Pat. App. & Inter. 1991) (human clinical data is not required to demonstrate the utility of the claimed invention, even though those skilled in the art might not accept other evidence to establish the efficacy of the claimed therapeutic compositions and the operativeness of the claimed methods of treating humans). Before a drug can enter human clinical trials, the sponsor, often the applicant, must provide a convincing rationale to those especially skilled in the art (e.g., the Food and Drug Administration (FDA)) that the investigation may be successful. Such a rationale would provide a basis for the sponsor’s expectation that the investigation may be successful. In order to determine a protocol for phase I testing, the first phase of clinical investigation, some credible rationale of how the drug might be effective or could be effective would be necessary. Thus, as a general rule, if an applicant has initiated human clinical trials for a therapeutic product or process, Office personnel should presume that the applicant has established that the subject matter of that trial is reasonably predictive of having the asserted therapeutic utility.
V. SAFETY AND EFFICACY CONSIDERATIONS
The Office must confine its review of patent applications to the statutory requirements of the patent law. Other agencies of the government have been assigned the responsibility of ensuring conformance to standards established by statute for the advertisement, use, sale or distribution of drugs. The FDA pursues a two-prong test to provide approval for testing. Under that test, a sponsor must show that the investigation does not pose an unreasonable and significant risk of illness or injury and that there is an acceptable rationale for the study. As a review matter, there must be a rationale for believing that the compound could be effective. If the use reviewed by the FDA is not set forth in the specification, FDA review may not satisfy 35 U.S.C. 101. However, if the reviewed use is one set forth in the specification, Office personnel must be extremely hesitant to challenge utility. In such a situation, experts at the FDA have assessed the rationale for the drug or research study upon which an asserted utility is based and found it satisfactory. Thus, in challenging utility, Office personnel must be able to carry their burden that there is no sound rationale for the asserted utility even though experts designated by Congress to decide the issue have come to an opposite conclusion. “FDA approval, however, is not a prerequisite for finding a compound useful within the meaning of the patent laws.” In re Brana, 51 F.3d 1560, 34 USPQ2d 1436 (Fed. Cir. 1995) (citing Scottv.Finney, 34 F.3d 1058, 1063, 32 USPQ2d 1115, 1120 (Fed. Cir. 1994)).
Thus, while an applicant may on occasion need to provide evidence to show that an invention will work as claimed, it is improper for Office personnel to request evidence of safety in the treatment of humans, or regarding the degree of effectiveness. See In re Sichert, 566 F.2d 1154, 196 USPQ 209 (CCPA 1977); In re Hartop, 311 F.2d 249, 135 USPQ 419 (CCPA 1962); In re Anthony, 414 F.2d 1383, 162 USPQ 594 (CCPA 1969); In re Watson, 517 F.2d 465, 186 USPQ 11 (CCPA 1975); In re Krimmel, 292 F.2d 948, 130 USPQ 215 (CCPA 1961); Ex parte Jovanovics, 211 USPQ 907 (Bd. Pat. App. & Inter. 1981).
VI. TREATMENT OF SPECIFIC DISEASE CONDITIONS
Claims directed to a method of treating or curing a disease for which there have been no previously successful treatments or cures warrant careful review for compliance with 35 U.S.C. 101. The credibility of an asserted utility for treating a human disorder may be more difficult to establish where current scientific understanding suggests that such a task would be impossible. Such a determination has always required a good understanding of the state of the art as of the time that the invention was made. For example, prior to the 1980’s, there were a number of cases where an asserted use in treating cancer in humans was viewed as “incredible.” In re Jolles, 628 F.2d 1322, 206 USPQ 885 (CCPA 1980); In re Buting, 418 F.2d 540, 163 USPQ 689 (CCPA 1969); Ex parte Stevens, 16 USPQ2d 1379 (Bd. Pat. App. & Inter. 1990); Ex parte Busse, 1 USPQ2d 1908 (Bd. Pat. App. & Inter. 1986); Ex parte Krepelka, 231 USPQ 746 (Bd. Pat. App. & Inter. 1986); Ex parte Jovanovics, 211 USPQ 907 (Bd. Pat. App. & Inter. 1981). The fact that there is no known cure for a disease, however, cannot serve as the basis for a conclusion that such an invention lacks utility. Rather, Office personnel must determine if the asserted utility for the invention is credible based on the information disclosed in the application. Only those claims for which an asserted utility is not credible should be rejected. In such cases, the Office should carefully review what is being claimed by the applicant. An assertion that the claimed invention is useful in treating a symptom of an incurable disease may be considered credible by a person of ordinary skill in the art on the basis of a fairly modest amount of evidence or support. In contrast, an assertion that the claimed invention will be useful in “curing” the disease may require a significantly greater amount of evidentiary support to be considered credible by a person of ordinary skill in the art. In re Sichert, 566 F.2d 1154, 196 USPQ 209 (CCPA 1977); In re Jolles, 628 F.2d 1322, 206 USPQ 885 (CCPA 1980). See also Ex parte Ferguson, 117 USPQ 229 (Bd. Pat. App. & Inter. 1957).
In these cases, it is important to note that the Food and Drug Administration has promulgated regulations that enable a party to conduct clinical trials for drugs used to treat life threatening and severely-debilitating illnesses, even where no alternative therapy exists. See 21 CFR 312.80-88 (1994). Implicit in these regulations is the recognition that experts qualified to evaluate the effectiveness of therapeutics can and often do find a sufficient basis to conduct clinical trials of drugs for incurable or previously untreatable illnesses. Thus, affidavit evidence from experts in the art indicating that there is a reasonable expectation of success, supported by sound reasoning, usually should be sufficient to establish that such a utility is credible.