Board of Patent Appeals and Interferences
Patent and Trademark Office (P.T.O.)
*1 FISHER ET AL.
v.
BOUZARD ET AL.
Patent Interference No. 101,067
January 12, 1987
Final Hearing January 16, 1986
The Crystalline Gluconate Salt of m-AMSA and Compositions Containing Same
Application of James R. Fisher and Charles P. Kulier filed September 16, 1981, Serial No. 302,944 Accorded Benefit of Serial No. 129,503 filed March 11, 1980.
Patent granted to Daniel Bouzard, Claude Perol, Jacques Stemer, Abraham Weber and Edmund S. Granatek on March 30, 1982, Patent No. 4,322,424 filed October 17, 1980, Serial No. 194,350 Accorded Benefit of Serial No. 114,809 filed January 24, 1980.
Graddis, Raines, S. Miller, Patton, Gillow, Flintoft, C. Miller, Ranalli and Friebel for Fisher et al.
Taylor, Jr., Morse, Lloyd, Uloth and Berdo for Bouzard et al.
Before Torchin, Smith and Sofocleous
Examiners-in-Chief
Smith
Examiner-in-Chief
This interference involves an application of Fisher et al. (hereinafter Fisher), Serial No. 302,944, filed September 16, 1981 and assigned to Warner-Lambert Co. and a patent of Bouzard et al. (hereinafter Bouzard), Patent No. 4,322,424, which is assigned to Bristol-Myers Company.
The subject matter at issue relates to the gluconate salt of m-AMSA and water-soluble compositions containing the gluconate salt of m-AMSA. The compositions possess antitumor activity and are suitable for intravenous administration to human patients. The counts at issue, Counts 2-9, read as follows:
Count 2
The gluconate salt of m-AMSA.
Count 3
A stable, solid, water-soluble composition for reconstitution with water or aqueous vehicle as a stable solution of m-AMSA, said composition comprising a mixture of about one mole of m-AMSA gluconate salt per 0.2 to 10 moles of an organic acid selected from the group consisting of gluconic acid, gluconolactone and mixtures thereof.
Count 4
The composition according to count 3 having about one mole of m-AMSA gluconate salt per about 1 to about 10 moles of organic acid.
Count 5
A stable, solid, water-soluble composition for reconstitution with water or aqueous vehicle as a stable solution of m-AMSA, said composition being produced by the steps of
(1) forming an aqueous solution of m-AMSA and an organic acid selected from the group consisting of gluconic acid, gluconolactone and mixtures thereof, the molar ratio of the organic acid to m-AMSA being from about 1.2:1 to about 11:1; and
(2) lyophilizing the so-produced aqueous solution.
Count 6
The composition according to count 5 wherein about 2 to about 11 moles of organic acid are used per mole of m-AMSA.
Count 7
The composition according to count 5 wherein the organic acid is selected from the group consisting of gluconic acid and gluconolactone.
Count 8
The composition according to count 6 wherein the organic acid is selected from the group consisting of gluconic acid and gluconolactone.
Count 9
*2 The composition according to count 5 wherein the aqueous solution of step (1) is formed by reacting about 5 to about 7.85 g. m-AMSA and a sufficient amount of an organic acid selected from the group consisting of gluconic acid and gluconolactone to produce a mole ratio of organic acid to m-AMSA of about 2.75:1 to about 8.5:1 per liter of solution.
The relation of the counts of the interference to the claims of the respective parties is as follows:
Counts Fisher Bouzard
------ ------ -------
2 5 1(m)
3 18(p) 2(p)
4 19(p) 3(p)
5 20(p) 4(p)
6 21(p) 5(p)
7 22(p) 6/4(p)
9 23(p) 7(p)
No issue of interference-in-fact has been raised.
Both parties filed briefs and both parties waived appearance at final hearing for oral argument.
Bouzard is senior party based on the January 24, 1980 filing date of his parent application Serial No. 114,809. Bouzard was accorded the benefit of his parent application when the interference was declared, and Fisher does not contest Bouzard's entitlement to that date. Fisher was accorded the benefit of the March 11, 1980 filing date of his parent application Serial No. 129,503 when the interference was declared and by the primary examiner in his Decision on Motions (Paper No. 35). Bouzard does not contest Fisher's entitlement to that date.
In accordance with a stipulation between the parties under 37 CFR 1.272(c) dated November 27, 1984, both parties submitted evidence in support of their case for prior invention in the form of a stipulation of facts and testimony in the form of affidavits (FR ix-xi). [FN1] Objections to evidence were reserved pursuant to an additional stipulation (FR xii).
The issue presented for our determination is priority of invention of the subject matter of the involved counts. Bouzard does not contest in his brief the evidence relied on by Fisher in support of the Fisher case for prior invention. Rather, Bouzard indicates on page 4 of his brief that the principal issues involved in this interference may be stated as follows:
1. Whether Bouzard et al. have established a reduction to practice of the subject matter of Count 2, i.e., the gluconate salt of m-AMSA, in this country prior to the earliest date alleged by Fisher et al.
2. Whether Bouzard et al. have proved a conception of the invention of the subject matter defined by Counts 5-9 prior to the earliest date which Fisher et al. are entitled to as to the subject matter of these counts and proved diligence from that date to the Bouzard et al. constructive reduction to practice.
*3 On page 12 of his brief Bouzard concedes priority as to the subject matter of Counts 3 and 4.
Motion To Deny Consideration
On September 27, 1986 Bouzard filed a paper entitled MOTION TO DENY CONSIDERATION OF PORTIONS OF JUNIOR PARTY'S REPLY BRIEF (Paper No. 73). The Bouzard motion was opposed by Fisher (Paper No. 74) and deferred to Final Hearing (Paper No. 75).
In his motion Bouzard asks the Board to deny consideration of certain portions of the Fisher reply brief because it 'contains new material not discussed in the junior party's main brief.' Bouzard notes that the portions of the Fisher brief with which the motion is concerned deal with affidavits in the record of Bouzard by Kaplan and Bradner and with rebuttal affidavits of Elslager and Mehta presented by Fisher. Bouzard urges that the Fisher main brief is devoid of a discussion of any of these affidavits, thereby failing to comply with the requirements of 37 CFR 1.254. [FN2]
As noted by Fisher in his opposition to the motion, the parties to this interference met and agreed on certain facts to be stipulated under 37 CFR 1.272(c) (FR ix-xi) and identified the proposed facts as to which they would not stipulate. Thereafter, according to the stipulation each party presented affidavit evidence as to facts to which the other party would not stipulate and the other party then filed rebuttal affidavits (FR ix-x). Fisher presented the rebuttal affidavits of Elslager and Mehta expressly stating facts and conclusions opposing those of Kaplan and Bradner. Both Elslager and Mehta aver that they have read the affidavits of Kaplan and Bradner and they present facts and reasoning in support of their conclusions contrary to those of Kaplan and Bradner.
Fisher urges that there was nothing 'new' or 'surprising' in the Fisher reply brief. He contends that his main brief is in compliance with 37 CFR 1.254 because it does present a statement of the questions involved, including his position with respect to the priority evidence of Bouzard. Fisher notes that his main brief offered his record, which included the rebuttal affidavits of Elslager and Mehta, into evidence on page 45 thereof and offered objections to the Kaplan and Bradner affidavits on page A-5. The Fisher main brief discusses the experience and credentials of affiants Elslager and Mehta on pages 8 and 9. It is Fisher's position that the material to which Bouzard objects is nothing more than a discussion of the facts set forth in the Elslager and Mehta affidavits in support of the positions taken in the main brief. Fisher urges that 37 CFR 1.254 does not require that the junior party present in his main brief all facts in support of his positions on the senior party's priority case. Rather, the junior party must, to the extent he is then able from the record, set forth the issues and his position respecting them. The detailed facts in support of those positions may be presented after the senior party provides his priority case.
*4 In determining whether the Fisher main brief complies with 37 CFR 1.254 we have considered the purpose of the rule as stated in Moller v. Harding, 214 USPQ 730 (Bd. Pat. Int. 1982), i.e., 'to provide the senior party opportunity to present his views on all grounds.' We believe that in the circumstances presented here, given the short record, the refusal to stipulate to certain facts creating specific factual issues, the presentation of the rebuttal affidavits of Elslager and Mehta with explicit references to the Kaplan and Bradner affidavits and the disputed 'facts' contained therein and Fisher's statement of the issues and his position in the main brief, Bouzard had opportunity to present his views on all of the Fisher positions. Accordingly, we are constrained to deny the motion to deny consideration to certain portions of the Fisher reply brief.
Bouzard's Case for Priority re Count 2
Bouzard notes in his brief that the earliest date that Fisher relies on in his brief for a conception of Count 2 is in June, 1979 (Fisher Brief, page 11). Bouzard does not contest the Fisher evidence of conception of Count 2 in June, 1979, nor does Bouzard contest the Fisher evidence of reduction to practice of the invention of Count 2 in July-August, 1979. Rather, Bouzard relies on evidence of certain activity on behalf of Bouzard in March, 1979 which is urged to establish a reduction to practice of the invention of Count 2 by Bouzard more than two months earlier than the earliest date relied on by Fisher.
Count 2 is directed to the 'gluconate salt of m-AMSA'. The stipulated facts establish that a sample of m-AMSA gluconate salt was prepared in France and sent on March 5, 1979 by D. Bouzard, one of the inventors, to Dr. Charles M. Combs of the Mead-Johnson Analytical Chemistry Department in Evansville, Indiana. According to the stipulated facts, the sample arrived in Evansville on March 14, 1979, accompanied by a structure sheet (BX B) giving the compound name and structure, molecular formula, molecular weight, color, analysis number, lab record number and sequence number and a cover sheet identifying the material by analysis number. It was further stipulated that the sample compound was analyzed by Dr. Combs (elemental, Karl Fisher H2O, NMR and mass spectrum) and the analytical data was consistent for the assigned structure of m-AMSA gluconate (BR 4).
In addition to the foregoing stipulated evidence of the importation of m-AMSA gluconate into this country in March, 1979 and the analytical testing performed by Dr. Combs, Bouzard relies on the affidavit opinions of Kaplanand Bradner in support of his position that the utility of the gluconate salt of m-AMSA was obvious as of March 14, 1979 and a method for making m-AMSA gluconate, though not required for a reduction to practice, would have been obvious as of March 14, 1979 in any event. It is Bouzard's position that the foregoing evidence is sufficient to establish a reduction to practice in this country in March, 1979 for the invention of Count 2.
Fisher's Position re Bouzard's Case for Priority-Count 2
*5 Fisher contends that the Bouzard evidence is insufficient to establish either a conception or a reduction to practice in this country in March, 1979. Fisher urges that the Bouzard evidence does not establish conception because, inter alia, a complete conception of a chemical compound requires an operative method of making the compound. Fisher notes that the documents imported into the United States on behalf of Bouzard do not include a method for making m-AMSA gluconate and Fisher argues that such a method would not have been obvious in March, 1979. Further, it is Fisher's position that the Bouzard evidence fails to establish an actual reduction to practice because Bouzard failed to demonstrate a practical utility for m-AMSA gluconate in March, 1979 and, indeed, did not even demonstrate the high water-solubility of m-AMSA gluconate. Moreover, Fisher urges that a practical utility would not have been obvious in March, 1979.
Fisher also sets forth in Appendix A of his main brief certain 'Objections to Record of the Party Bouzard'. In this connection we note that it is well settled that when a party intends to rely on objections to an opponent's testimony, he must file a motion to suppress or strike the allegedly improper testimony. Cf. III Rivise and Caesar, Interference Law and Practice, §§ 452- 454 (Michie Co. 1947) and Photis v. Lunkenheimer, 225 USPQ 948 (Bd. Pat. Int. 1984). The mere listing of objections in an appendix does not, in our view, provide an adequate briefing of the issues as is contemplated by the requirement for a motion to suppress. [FN3] Moreover, since Fisher has stipulated pursuant to 37 CFR 1.272(c) to certain facts which are included in the Bouzard record and has stipulated that Bouzard may present additional evidence in the form of affidavits of witnesses in lieu of testimony, Fisher is in no position to object to the admissibility of those facts and affidavits. III Rivise and Caesar, Interference Law and Practice, § 452 (Michie Co. 1947). Accordingly, we have considered the Fisher 'objections', to the extent that we can understand them in the absence of an adequate briefing, only as they relate to the weight and sufficiency of the Bouzard evidence.
Opinion re Bouzard's Case for Priority-Count 2
We hold that Bouzard has failed to prove a reduction to practice of the invention of Count 2 in March, 1979 or at any time prior to the dates relied on by Fisher.
We agree with Fisher that Bouzard must establish that the compound introduced into this country was accompanied by an enabling disclosure of how to prepare the compound in order to be credited with either conception or actual reduction to practice of the compound. Breuer v. DeMarinis, 558 F.2d 22, 194 USPQ 308 (CCPA 1977); Thomas v. Eicken, 219 USPQ 900 (Bd. Pat. Int. 1983) and Broadhead v. McCracken, 167 USPQ 179 (Bd. Pat. Int. 1970). Note also I Rivise and Caesar, Interference Law and Practice, §§ 111 and 132 (Michie Co. 1940) for the prerequisites of conception and of actual reduction to practice. An actual reduction to practice must include 'every essential feature of the invention as defined in the count of the interference' and where the count is drawn to a chemical compound it is well settled that an essential feature of the invention is a method for preparing the compound.
*6 Bouzard acknowledges that the importation of m-AMSA gluconate in March, 1979 was not accompanied by a method for the preparation of the compound, but argues that such a method would have been obvious in March, 1979. In support of his argument Bouzard relies on the affidavit of Kaplan. Kaplan refers to an article by Cain et al. in the Journal of Medicinal Chemistry and avers that at page 129 of the article there is disclosed a procedure by which m-AMSA free base is suspended in anhydrous methanol and methane sulfonic acid was added to form the methane sulfonate salt. Kaplan states that from the teachings of the article and from his general knowledge of the formation of salts from free bases, he is of the opinion that 'as of March 14, 1979, a worker skilled in the art would expect that some amount of the gluconate salt of m-AMSA could be prepared by substituting gluconic acid and/or gluconolactone for the methane sulfonic acid in the procedure set forth on page 929 of this article' (BR 12- 13).
In their rebuttal affidavits, Elslager and Mehta, conclude that it would not have been obvious to prepare m-AMSA gluconate following the procedure of Cain et al. They both aver that the Cain et al. article does not even describe m- AMSA, but rather describes various substituted acridylmethanesulfonanilides. Both Elslager and Mehta opine that it would not have been obvious to substitute gluconic acid, a weak acid, for methanesulfonic acid, a strong acid, in any case. Further, both Mehta and Elslager opine that it would not have been obvious to utilize anhydrous methanol solvent, as taught by the Cain et al. article, to react m-AMSA with gluconic acid because m-AMSA free base and D-gluconic acid are only slightly soluble in anhydrous methanol. (FR 85-90, 99- 101).
Bouzard, as the proponent of an actual reduction to practice in March, 1979, has the burden of proof by a preponderance of the evidence. We have carefully considered the evidence relied on by Bouzard and the rebuttal evidence submitted by Fisher. In our opinion Bouzard has not met his burden of proof on the issue of whether a method for preparing m-AMSA gluconate would have been obvious to one skilled in the art in March, 1979. Accordingly, we hold that Bouzard has not established that a method for preparing m-AMSA gluconate would have been obvious in March, 1979.
Bouzard's case for actual reduction to practice also fails, in our view, because Bouzard did not establish a practical utility for m-AMSA gluconate in March, 1979. It is well settled that a practical utility must be established for a novel compound before it can be said to have been reduced to practice. Kawai v. Metlesics, 480 F.2d 880, 178 USPQ 158 (CCPA 1973) and Rebstock v. Flouret, 191 USPQ 342 (Bd. Pat. Int. 1975). As noted, supra, Bouzard conducted no tests in March, 1979 to establish the practical utility of m-AMSA; rather, Bouzard urges that the utility of m-AMSA gluconate was obvious as of March, 1979, based on the affidavit opinions of Kaplan and Bradner.
*7 There is some precedent for obvious utility of a compound based on its properties or similarity to known compounds. For example, in Breen v. Miller, 52 CCPA 1539, 347 F.2d 623, 146 USPQ 127 (1965) the Court held that:
The filament in question so closely resembles previously known filaments of organic polymers, i.e., nylon, that it obviously would be useful for the same purpose as such filaments.
Also, in Kyrides v. Bruson, 26 CCPA 986, 102 F.2d 416, 41 USPQ 107 (1939) the Court held that tests of the particular composition of matter involved were not necessary, but that holding was based on the ground that the composition was 'of admitted utility' and that 'If the ester was formed, it was known to have utility as a plasticizer.' In Blicke v. Treves, 44 CCPA 753, 241 F.2d 718, 112 USPQ 472 (1957) the Court distinguished the situation it faced with that in Kyrides, supra, and held that tests were required as follows:
It is evident that, while the antispasmodic properties of a new meterial might be reasonably deduced from its similarity to known antispasmodics, they could not be foretold with certainty; and that fact is apparent from the record here which shows that appellant and his associates subjected the new material to very extensive tests.
The situation here is analagous to that in Blicke, in our opinion, i.e., it is not sufficient to establish a reduction to practice for an expert to assert an opinion that he would have expected the gluconate salt of m-AMSA to have some antitumor activity. The compound involved here is a new compound and it has not been shown that the antitumor activity could have been foretold with certainty; indeed, Bouzard has not even addressed this issue. Accordingly, we hold that the instant compound was not reduced to practice by the mere importation of the compound; rather, sufficient testing to establish the practical utility of the compound is required. [FN4]
Bouzard urges on pages 7 and 8 of his brief that the situation here is similar to that in Silvestri v. Grant, 496 F.2d 593, 181 USPQ 706 (CCPA 1974), where the Court held that the utility of a new crystalline form of ampicillin would have been obvious since 'There is no reason to believe that the crystal structure and absence or presence of bound water would affect the pharmacological properties of ampicillin'. We agree with Fisher that the holding in Silvestri is inapplicable here. In Silvestri the Court emphasized in reaching its decision that a new compound was not involved, rather a new form of an old one, i.e., ampicillin. In contrast, the situation here involves a new compound and the reasoning in Silvestri is therefore not controlling.
Bouzard's Case for Priority re Counts 5-9
*8 Bouzard urges that he is entitled to an award of priority as to Counts 5-9 if he has established (1) that he was the first to conceive the invention and (2) that he was diligent in reducing the invention to practice from a time just prior to the time Fisher entered the field, i.e., his conception date, to the time of Bouzard's constructive reduction to practice. Bouzard contends that he is entitled to a date of conception for Counts 5-9 of October 22, 1979 when a complete description of the subject matter of these counts was received in this country from one of the senior party co-inventors; that this date is prior to any date to which Fisher is entitled as to these counts; and that his attorney, David M. Morse, was diligent in the preparation of the patent application up to the time of its filing in the Patent and Trademark Office on January 24, 1980.
Bouzard rests his case for prior conception, based on his October 22, 1979 date, on an interpretation of Fisher's preliminary statement. Bouzard notes that Fisher made the following allegations in his preliminary statement:
The invention of Counts 5-8 was first disclosed to another person or persons on or about November 5, 1979 or shortly thereafter, but no later than November 12, 1979.
The invention of Count 9 was first disclosed to another person or persons on or about January 7, 1980 but no later than February 7, 1980.
Based on these allegations, Bouzard urges that the earliest dates which can be accorded Fisher for conception are those alleged for disclosure to another person (November 12, 1979 for Counts 5-8 and February 7, 1980 for Count 9) and that if Fisher proves any date earlier than those dates alleged in their preliminary statement, such proof will establish the dates so alleged and none earlier. 37 CFR 1.223(b).
Opinion re Bouzard's Case for Priority-Counts 5-9
We disagree with the contentions of Bouzard that the earliest dates that can be accorded Fisher for conception are November 12, 1979 for Counts 5-8 and February 7, 1980 for Count 9. Bouzard has overlooked the following allegations made by Fisher in his preliminary statement:
Counts 5 through 8
4) The date of the first act or acts susceptible of proof (other than making a drawing or written description or disclosing the invention to another person) which, if proven, would establish conception of the invention were on or about June 21, 1979, on which date the m-AMSA gluconate salt was actually reduced to practice;
***
Count 9
4) The date of the first act or acts susceptible of proof (other than making a drawing or written description or disclosing the invention to another person) which, if proven, would establish conception of the invention were on or about June 21, 1979, on which date the m-AMSA gluconate salt was actually reduced to practice;
The foregoing allegations by Fisher in his preliminary statement provide an adequate basis for Fisher to present evidence of acts which, if proven, would establish conception by Fisher as early as June 21, 1979. To hold otherwise would render the rule [FN5] a nullity. We know of no authority that would restrict the dates that may be accorded a party for conception to the dates alleged for the first disclosure to another person, when that party has alleged an earlier date for conception based on earlier acts which would establish conception, if proven. Moreover, it would be manifestly inequitable to ignore Fisher's allegations and evidence of earlier acts which, if proven, would establish conception.
*9 An examination of the Fisher record and the Fisher main brief indicates that Fisher has presented evidence of acts relied on to establish conception of the subject matter of Counts 5-9 prior to the October 22, 1979 date of Bouzard's purported conception. Fisher presented corroborated evidence of the preparation of m-AMSA gluconate in June, 1979 (FR 4-5). Fisher presented corroborated evidence of the conception and reduction to practice of the composition of Counts 3 and 4 during the period of July through September, 1979 (cf. Fisher Brief, pages 19-24), and Bouzard has conceded priority as to those counts. Counts 5-9 add to the requirements of Counts 3 and 4 that the m-AMSA gluconate-containing composition is prepared by lyophilization, i.e., by freeze drying, rather than the normal evaporation utilized by Fisher and his coworkers in the reduction to practice of Counts 3 and 4. Fisher testified that he conceived of the preparation of the m-AMSA gluconate composition by lyophilization at least by August 17, 1979, when he requested that the Product Development Group conduct formulation studies on m-AMSA gluconate (FR 27-30). He knew that the standard procedures used in formulation studies would include lyophilization. The request for formulation studies and the fact that such studies include lyophilization are corroborated in the Fisher record. Fisher has also presented evidence of three corroborated actual reductions to practice of the invention of Counts 5-9 prior to Bouzard's constructive reduction to practice (cf. Fisher Brief, pages 28-31).
We have carefully reviewed all the evidence submitted by Fisher. We agree with Fisher that the evidence is adequate to meet his burden of proof as to conception of Counts 5-9 prior to the October 22, 1979 date asserted by Bouzard and as to actual reduction to practice of Counts 5-9 prior to Bouzard's constructive reduction to practice on January 24, 1980. The evidence has not been challenged in any way by Bouzard, except that Bouzard has contended that Fisher is limited for conception to the date alleged in his preliminary statement for first disclosure to another, and we have indicated our disagreement with that contention, supra.
JUDGMENT
For the foregoing reasons, priority of invention of the subject matter of Counts 2-9 is awarded to James R. Fisher and Charles P. Kulier, the junior party.
BOARD OF PATENT AAPPEALS AND INTERFERENCES
Norman G. Torchin
Examiner-in-Chief
Ronald H. Smith
Michael Sofocleous
Examiner-in-Chief
FN1. References to the Fisher record will be designated FR and references to the Bouzard record will be designated BR. Similarly, Fisher's exhibits will be designated FX and Bouzard's exhibits will be designated BX.
FN2. 37 CFR 1.254 provides, inter alia, as follows: The brief for the junior party shall present a full, fair statement of the questions involved, including his position with respect to priority evidence on behalf of other parties, and a clear statement of the points of law or fact upon which he relies.
FN3. Note the requirements of 37 CFR 1.243 for motions before the Board of Patent Interferences that such motions '. . . shall contain a full statement of the action sought and the grounds therefor . . .' and 'Briefs or memoranda in support of such motions shall accompany the motion.'
FN4. Moreover, even assuming, arguendo, that this was a situation where an obvious utility would have been sufficient for a reduction to practice, it is our view after evaluating the conflicting evidence that Bouzard has not met his burden of proof on the issue of whether a utility for m-AMSA gluconate would have been obvious to one skilled in the art.
FN5. 37 CFR 1.216 requires that preliminary statements contain an allegation of the first acts which, if proven, would establish conception.
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