Board of Patent Appeals and Interferences
Patent and Trademark Office (P.T.O.)
*1 HOFFMAN ET AL.
KLAUS ET AL.
Patent Interference No. 101,437
January 7, 1988
Application of William W. Hoffman and Allen R. Kraska filed July 5, 1983, Serial No. 511,037.
Application of Michael Klaus and Peter Loeliger filed May 5, 1983, Serial No. 491,618.
Knuth, Frost, Spiegel, Richardson, Monroe, Lumb, Akers, McManus, Thomas, Bloom, Cantey, Blackwood, Ordway, Connolly, Bakalar, Bower, Hutz, Pezzner, Fairchild, Beck, Crawford and Foster for Hoffman et al. Oral Argument by Rudolf E. Hutz
Saxe, Leon, Gould, Epstein and Isgro for Klaus et al. Oral argument by William H. Epstein
Before Torchin, Smith and Skinner
The Klaus et al. (Klaus) application is assigned to Hoffman-LaRoche, Inc. (Hoffman-LaRoche), and the Hoffman et al. (Hoffman) application to Pfizer, Inc. (Pfizer). Both parties filed briefs and appeared, through counsel at final hearing.
The subject matter in issue is defined by the following single count:
TABULAR OR GRAPHIC MATERIAL SET FORTH AT THIS POINT IS NOT DISPLAYABLE
X is O, S, SO or SO@2;
R@1 and R@2 are independently H or CH@3;
Z is H or F, with the proviso that Z is F
only when R@2 is CH@3;
Z@1 is H, OH, OCH@3 or F;
n is 0 or 1;
Y is OH, OR@3 wherein R@3 is alkyl or aryl,
or NR@4R@5 wherein R@4 is H, alkyl or aryl and R@5 is H, alkyl, aryl or 5-tetrazolyl, the alkyl groups
being optionally substituted by an OH or alkoxy, and the R@4 and R5 aryl groups being optionally substituted by an OH, alkyl, hydroxyalkyl or alkoxy;
or a pharmaceutically acceptable salt thereof.
Corresponding to the count are claims 1-14 of Hoffman and claims 46-53, 60, 62- 73 and 82-85 of Klaus.
Hoffman has taken testimony, pursuant to 37 CFR 1.672(b), in the form of affidavits (HR), accompanied by exhibits (HX), in an attempt to establish he was the first to invent. Klaus has taken testimony, also in the form of affidavits (KR), in rebuttal.
The facts are adequately set forth at pages 2-8 of Hoffman's brief, Facts Nos. 1-9. We adopt them as our own findings of fact and incorporate them here by reference. [FN1]
Klaus does not question that by August 19, 1980, Hoffman had prepared a compound, identified in the Hoffman record as "CP-57,850", within the scope of the count. Rather, he urges that there was no prior reduction to practice because Hoffman had not established utility for the compound prior to Klaus' effective filing date. Thus, the sole issue before us is whether Hoffman's evidence demonstrates a utility for CP-57,850 sufficient to establish a complete reduction to practice. [FN2]
As is apparent, the count sets forth no utility for the compounds. Thus, evidence establishing a substantial utility for any purpose is sufficient to show reduction to practice. Rey-Bellet v. Englehardt, 493 F.2d 1380, 181 USPQ 453 (CCPA 1974). According to Hoffman's disclosure, the compounds "are useful for inhibiting degradation of articular cartilage when administered to a mammalian subject afflicted with an arthritic disease." (Specification, p. 1). The utility alleged by Hoffman with respect to his reduction to practice concerns the property of collagenase inhibition.
*2 Briefly, compounds under consideration as collagenase inhibitor candidates were tested with a then standard Pfizer procedure known as "PROC 168-A." (Fact No. 6). The testing procedure was entitled "Anti-Collagenase Screen 168-A," the details of which appear in HX I and II. (Fact No. 7). It is an in vitro test procedure which measures the ability of chemical substances to inhibit the production of collagenase in synovial cell cultures from arthritic rabbits. The test included a control, with comparisons being made with indomethacin and dexamethsone, two commercially available analgesics and anti-inflammatory agents. For each of the concentrations at which CP-57,850 was tested, as well as for indomethacin and for dexamethasone, the amounts of collagenase produced were less than 0.50 units/million cells, whereas significant amounts were produced in the control experiment. (HX II, VII, and the testimony related thereto).
From those experiments, the inventors concluded that the compound was active as an inhibitor for production of collagenase. (HR 8, 12). Dr. Hoffman, one of the coinventors, testified (HR 8):
Based on the results shown in [HX II], I concluded that on or somewhat before August 9, 1980 that CP-57,850, a compound of the count of Interference No. 101,437, is active as an inhibitor of the production of collagenase. From this I concluded that CP-57,850 would inhibit the degradation of articular cartilage in mammal subjects.
In rebuttal, Klaus submitted testimony from Drs. Rhymer and Salvador, two qualified experts and employees of Hoffman-LaRoche. According to their testimony, there is no pharmaceutical marketed with the approved indication that it is useful for inhibiting collagenase production, and that it was, and still is, not known if the property of inhibiting collagenase production can be translated into a pharmaceutical useful in the treatment of arthritis, or for any other purpose. See, e.g., KR 1-3. Both experts specifically contradicted Dr. Hoffman's conclusion regarding the inhibition of the degradation of articular cartilage. (KR 4, 23).
Dr. Salvador had for a five year period conducted studies with regard to compounds and formulations preventing the degradation of collagen to determine the applicability of this property to their use in the treatment of arthritis in mammals. (KR 22). He testified that based upon the results of the simple in vitro tests of Hoffman (KR 23) ...
one could not predict if CP 57,850 would be active to inhibit the production of collagenase in vivo in mammalian subjects much less conclude that CP-57,850 would act in vivo in mammalian subjects to inhibit the degradation of articular cartilage.
Dr. Salvador further testified (KR 26-7)) that though both indomethacin and dexamethasone are anti-inflammatory agents, they are not marketed with an indication for use in inhibiting the production of collagenase or for inhibiting the degradation of articular cartilage in mammals. Therefore, he concluded (KR 27), the results obtained with CP-57,850 ...
*3 can not be correlated with known drugs which have been indicated as being useful as an inhibitor for the production of collagenase much less indicated as inhibiting the degradation of articular cartilage in mammals.
We find that Hoffman has not established the necessary practical utility for a complete prior actual reduction to practice.
Both parties discuss the leading case of Nelson v. Bowler, 626 F.2d 853, 206 USPQ 881 (CCPA 1980). In support of his position Hoffman points to the following (206 USPQ at 883):
Even though Nelson now admits that antifertility activity such as luteolysis is not proven by these tests, the board erred in not recognizing that tests evidencing pharmacological activity many manifest a practical utility even though they may not establish a specific therapeutic use.
"Practical utility" is a shorthand way of attributing "real-world" value to claimed subject matter. In other words, one skilled in the art can use a claimed discovery in a manner which provides some immediate benefit to the public.
Knowledge of the pharmacological activity of any compound is obviously beneficial to the public. It is inherently faster and easier to combat illnesses and alleviate symptoms when the medical profession is armed with an arsenal of chemicals having known pharmacological activities. Since it is crucial to provide researchers with an incentive to disclose pharmacological activities in as many compounds as possible, we conclude that adequate proof of any such activity constitutes a showing of practical utility.
However, we do not agree with Hoffman that Nelson permits the screening tests shown here to qualify as a "practical utility." In the paragraph immediately subsequent to the quotation, supra, relied upon by Hoffman, the court pointed out that "[A] rigorous correlation is not necessary where the test for pharmacological activity is reasonably indicative of the desired response." (Emphasis added). The court went on the distinguish the facts there from those in Rey-Bellet v. Englehart, supra, which decision, in our view, is clearly apposite to the facts before us here.
The court in Nelson noted with respect to Rey-Bellet that while Engelhardt advocated that pupil dilation evidenced anti-cholinergic activity, adequate correlation between them was not evidenced. Nor, in Rey-Bellet, was correlation between the "tetrabenaziene antagonism" test and antidepressant activity evidenced. Concluded the court in Nelson (206 USPQ at 884 emphasis added):
We find Rey-Bellet to be distinguishable on its facts. According to the present evidence, specific pharmaclological activities, i.e., smooth muscle stimulation and blood pressure modulation, were recognized as practical utilities. These activities were directly measured by dispositive tests. In other words, one skilled in the art at the time the tests were performed would have been reasonably certain that 16-phenoxy PG's had practical utility.
*4 The court in Nelson also distinguished over another one of their decisions, Knapp v. Anderson, 477 F.2d 588, 177 USPQ 688 (CCPA 1973). In that case, a claimed amine was alleged to be useful as an ashless dispersant in lubricants for internal combustion engines. The court in Knapp found that one skilled in the art would not find a practical utility solely in the results of a test for sludge dispersancy. One could not reasonably predict a practical utility therefrom, the court noted in Nelson (206 USPQ at 885), because the "losing party failed to establish a correlation between performance in the bench test and that within an engine." Concluded the Nelson court (ibid.),
Here, however, a correlation between test results and pharmacological activities has been established. The BP test inherently was of such a nature since it is performed in vivo and directly evidences the claimed activity. While the GC-SMS test is in vitro, both parties admit that it adequately simulates in vivo colon smooth muscle stimulation.
We find no evidence before us here that one skilled in the art at the time the tests were performed would have been reasonably certain that merely because CP-57,850 inhibited the production of collagenase in the in vitro test, it had practical utility. There is no evidence that there was a correlation between the tests and the treatment of arthritis or for any other useful purpose.
Indeed, the evidence adduced by Klaus is to the contrary. Klaus' experts make it clear that such compounds were not known to have the necessary correlation required in Nelson, Rey-Bellett and Knapp. The conclusions of Drs. Rhymer and Salvador have not been rebutted, or seriously questioned, by Hoffman. Though Dr. Hoffman testified that he concluded the compound would inhibit the degradation of articular cartilage, there is no supporting evidence for his conclusion vis-a-vis the art. Nor does Hoffman explain in his brief why we should accept Dr. Hoffman's testimony in face of the unrebutted testimony submitted by Klaus' witnesses.
We do not agree with Hoffman (reply brief, p. 2) that, under the circumstances of this case, the testimony of Drs. Rhymer and Salvator should be given "minimal weight due to the interested nature of the witnesses." In the absence of rebutting evidence, or an explanation as to why the conclusions reached in the testimony might be unreasonable, we find no reason to reduce the weight of the testimony. The correctness of Klaus' witnesses is seemingly demonstrated by the absence of argument in the Hoffman briefs directed to establishing a contrary view. Cf. Cislak v. Wagner, 215 F.2d 273, 103 USPQ 39, 41 (CCPA 1954).
Nor do we agree with Hoffman that his position is supported by the holding in Cross v. Iizuka, 753 F.2d 1040, 224 USPQ 739 (Fed.Cir.1985). The issue was whether there was a constructive reduction to practice in the Japanese benefit application. Though a specific therapeutic use may not have been established for certain, the disclosure did make a correlation between the use--"treatment of inflammation, thrombus, hypertension, cerebral apoplex, asthma, etc." (224 USPQ at 742)--and the tests. The correlation was held to be reasonable because of the structural similarity between the compounds of the count and those known to have the utility. The court noted (224 USPQ at 746), "Cross has failed to proffer sufficient evidence or present any persuasive arguments going to the question of significant structural dissimilarites...." Here, no such correlation was established and Hoffman did indeed present evidence to the contrary.
*5 As the court noted in Nelson (206 USPQ at 885), "[E]very utility question arising in an interference must be decided on its own facts." The facts before us convince us that the necessary correlation has not been made.
In view of the foregoing, JUDGMENT is hereby awarded to Michael Klaus and Peter Loeliger the senior party.
Accordingly, based on the present record,
(1) Klaus et al. are entitled to a patent containing claims 46-53, 60, 62-73 and 82-85 corresponding to the count.
(2) Hoffman et al. are not entitled to a patent containing claims 1-14 and 24 corresponding to the count.
BOARD OF PATENT APPEALS AND INTERFERENCES
Norman G. Torchin
Ronald H. Smith
FN1. "Klaus agrees in principle with the statement of facts as set forth in Hoffman's with respect to ... preparing and idenfiying a compound falling within the count ... CP-57,850." (Klaus brief, p. 5).
FN2. Another issue raised by Klaus in his brief--abandonment supression or concealment by Hoffman--was withdrawn during oral argument. Klaus had not complied with 37 CFR 1.632. See § 1.654(c).