Board of Patent Appeals and Interferences
Patent and Trademark Office (P.T.O.)
*1 SUH ET AL.
HOEFLE ET AL.
Interference No. 101,613
April 30, 1991
Final Hearing: November 8, 1990
Application of John T. Suh, Jeffrey N. Barton and John R. Regan, filed March 19, 1981, Serial No. 245,407.
Patent granted to Milton L. Hoefle and Sylvester Klutchko on August 17, 1982, Patent No. 4,344,949 filed February 20, 1981, Serial No. 236,397. Accorded benefit of Serial No. 193,767 filed October 3, 1980.
Gerald Sobel, Gerard F. Diebner and Joseph M. Manak, John F. Scully, Anthony C. Scott, Stephen D. Murphy, Leopold Presser, Peter G. Dilworth, William C. Roch, Ernest B. Lipscomb and Leon E. Tenebaum for Suh et al. Oral argument by Gerald Sobel
Gerald J. Flintoft, Charles Miller, Ann Gisolfi, Thomas Rowan, Albert H. Graddis, Stephen Raines, Stephen I. Miller, Walter Patton and Louis S. Gillow for Hoefle et al. Oral argument by Gerald J. Flintoft
Before Seidleck, Sofocleous and Caroff
This interference involves an application of Suh et al. (Suh), assigned to Rorer Pharmaceutical Corporation, and a patent of Hoefle et al. (Hoefle), assigned to Warner-Lambert Company.
The interference concerns certain substituted acyl derivatives of 1,2,3,4- tetrahydroisoquinoline-3-carboxylic acid. The compounds are useful as antihypertensive agents in the treatment of hypertension. Renin, an enzyme from the kidney, acts upon angiotensinogen, a pseudoglobulin in the blood plasma, to produce angiotensin I, a decapeptide. Angiotensin I is converted by angiotensin converting enzyme to angiotensin II, a potent vasoconstrictive agent which causes hypertension. If the formation of angiotensin II can be prevented, high blood pressure can be controlled. The compounds of this interference inhibit the breakdown of angiotensin I to angiotensin II, thus controlling high blood pressure. The subject matter in issue is defined by count 1 as follows:
A substituted acyl compound of 1,2,3,4-tetrahydroisoquinoline having the formula
TABULAR OR GRAPHIC MATERIAL SET FORTH AT THIS POINT IS NOT DISPLAYABLE
R and R@2 are hydrogen, C@1-C@6 alkyl, or phenyl C@1-C@6 alkyl; R@1, R@4, R@5, R@6 and R@7 are independently hydrogen, C@1-C@6 alkyl, C@2-C@6 alkenyl, C@2 -C@6 alkynyl, C@6-C@10 aryl, fused C@6-C@10 aryl-cyclo C@3-C@7 alkyl, C@6-C@10 aryl C@1-C@6 alkyl, cyclo C@3-C@7 alkyl, or heterocyclic selected from the group consisting of pyridinyl, piperidinyl, morpholinyl, pyrrolyl, pyrrolidinyl, thiamorpholinyl, quinolinyl, isoquinolinyl, tetrahydroquinolinyl, thiazolindinyl, thiazolinyl, thiazolyl, imidazolidinyl, imidazolinyl, imidazolyl, thiophenyl, tetrahydrothiophenyl, furyl and tetrahydrofuryl, wherein the alkyl, alkenyl, and alkynyl groups may carry substituents selected from the group consisting of hydroxy, C@1-C@6 alkoxy, halo, amino, C1-C@6 alkylamino, thio and C@1-C@6 alkylmercapto, the cycloalkyl groups may carry substituents selected from the group consisting of C@1-C@6 alkyl, halo, halo C@1-C@6 alkyl, hydroxy, C@1-C@6 alkylamino, nitro and trifluoromethyl, and the aryl and heterocyclic groups may carry substituents selected from the group consisting of C@1-C@6 alkyl, hydroxy, C@1-C@6 alkoxy, hydroxy C@1-C@6 alkyl, halo, thio, C@1 -C@6 alkylmercapto, thio C@1-C@6 alkyl, halo C@1-C@6 alkyl, amino, C@1-C@6 alkylamino, amino C@1-C@6 alkyl, nitro, methylenedioxy, and trifluoromethyl;
*2 R@3 is hydrogen, C@1-C@6 alkyl, C@2-C@6 alkenyl, C@2 -C@6 alkynyl, nitro, amino, C@1-C@6 alkylamino, di C1-C@6 alkylamino, hydroxy, C@1-C@6 alkoxy, thio, C@1 -C@6 alkoxy, thio, lower alkylthio, lower alkylsulfinyl, C@1-C@6 alkylmercapto, lower alkylsulfonyl, hydroxy C1-C@6 alkyl, thio C1-C@6 alkyl, halogen, halo C@1-C@6 alkyl, amino C@1-C@6 alkyl, C@1-C@6 alkylamino C@1-C@6 alkyl, di C@1-C@6 alkylamino C@1-C@6 alkyl, sulfonamido, methylenedioxy, or trifluoromethyl and, where there is more than one R3 group, the groups may be same or different;
n is an integer from 1 to 4 inclusive; and the pharmaceutically acceptable salts thereof.
Suh's claims 2 to 26 and Hoefle's claims 1 to 4, 14 and 15 correspond to the count. No question of interference-in-fact or separate patentability of claims in accordance with 37 CFR 1.633(b) and (c)(3) and (4) has been raised.
In the Decision on Preliminary Motions, the examiner-in-chief (EIC) granted, inter alia, Hoefle's preliminary motion under 37 CFR 1.633(c)(4) to designate claims 5 to 13 as not corresponding to the count and Hoefle's preliminary motion under 37 CFR 1.633(f) for benefit of his U.S. parent application. Suh opposed both motions. After rendering the decision, the EIC set times for both parties to present priority testimony. After the close of Hoefle's testimony period, Suh filed motions (Paper Nos. 121 to 123) to compel the testimony of the senior party's inventors and for additional discovery. In the order of March 13, 1989, the EIC denied the motions and a panel of this Board denied Suh's request for reconsideration of the order. Subsequently, Suh presented rebuttal testimony and filed a belated preliminary motion (Paper No. 177) for judgment. Both parties filed records and briefs and appeared, through counsel, at final hearing.
Suh's and Hoefle's Motions to Suppress
Each party filed with its brief a motion [FN1] to suppress portions of its opponent's record. Oppositions and replies were filed with respect to the motions. Each motion will be considered, infra, insofar as it relates to the exhibits and testimony discussed herein.
Hoefle's Motion to Strike Suh's Reply Brief
Before us for consideration is Hoefle's motion (Paper No. 216) to strike certain sections of Suh's reply brief. Suh has filed an opposition thereto.
The motion requests that four sections of Suh's reply brief be stricken or denied consideration.
The first concerns pages 2 to 3, Section II and pages 23 to 28, Section B. The motion states that the reply brief is attempting to alter the facts without addressing any points raised in Hoefle's brief by urging that Suh's conception is for a broad class of dipeptide compounds, an argument which, according to Hoefle, should have been presented in Suh's main brief. In his opposition, Suh states that he has merely amplified an argument appearing on pages 74 to 77 of his main brief.
greatly changed priority case which improperly introduces new positions and arguments which do not refute any points raised in Hoefle's opening brief.
by alleging a successful preparation of a compound within the count by Barton. The motion contends that this is a new position which suggests that Suh possessed a method for synthesizing a compound of the count earlier than alleged. In his opposition, Suh states that this is not a new position because the argument presented here is fully set forth in the opening brief at pages 100, 101, and 107 to 116.
The third concerns pages 6 to 19, Section IV and page 30 to page 38, first paragraph, Section C. The motion states that the reply brief is presenting a new argument to support its conception case
by adopting the teaching in an article by Cushman et al. [appearing in a book entitled, "Angiotensin Converting Enzyme Inhibitors"] as being the mental processes of the inventor, Dr. Suh.
The motion contends that, according to Suh, the book shows the state of the art in May of 1980. In his opposition, Suh states that the publication, which was introduced under 37 CFR 1.682, is properly in evidence and discussed in the main brief at pages 39 to 42.
The fourth concerns pages 38 to 51, entitled "Hoefle's Conception." The motion states that the reply brief raises for the first time an evidentiary (alleged hearsay) issue relating to Hoefle's conception which should have been done in Suh's opening brief. In his opposition, Suh urges that he is entitled to argue any
supportable, factual or legal principal it desires in an effort to refute the conception case proffered by the senior party, which case was presented for the first time by the senior party principal Brief. This is the purpose of a Reply Brief. The fact that Suh, et al. attack the Hoefle, et al. conception on various grounds including evidentiary grounds does not mean that Hoefle, et al. are entitled to present additional argumentation.
Opinion re: Hoefle's Motion
Pursuant to 37 CFR 1.656(b), the opening brief of the junior party must contain a statement of the issues presented for decision, a statement of the facts relevant to the issues and an argument which shall contain the contentions of the party with respect to the issues and the reasons therefor. The purpose of the rule is to provide the senior party an opportunity to present his views on all grounds. Cf. Fisher v. Bouzard, 3 USPQ2d 1677 (BPAI 1987); Moller v. Harding, 214 USPQ 730 (Bd.Pat.Int.1982).
Bearing this principle in mind, we agree with Hoefle that the objection to the fourth section, i.e., pages 38 to 51 of the reply brief, is well taken. In this section, Suh raises for the first time a hearsay issue with respect to Hoefle's case for conception. This issue should have been presented earlier in Suh's opening brief in accordance with 37 CFR 1.656(b). Nowhere in his opposition does Suh contend that this issue was so presented in his opening brief. Since new material does not belong in the reply brief, see, inter alia, Photis v. Lunkenheimer, 225 USPQ 948 (Bd.Pat.Int.1984), the motion is granted to the extent that we will not consider the issue.
*4 With respect to the objections to the first three sections, the motion is denied. Since we find support for these sections in Suh's opening brief, we do not agree with Hoefle that new arguments are being presented. Accordingly, these sections of the reply brief are entitled to consideration.
During oral argument, Suh withdrew the request in his brief that we review the EIC's decision concerning the designation of Hoefle's claims 5 to 13 as not corresponding to the count. Accordingly, we will not consider the issue.
The Hoefle brief raises an issue of inequitable conduct, which we will not consider. It is the policy [FN2] of the PTO not to consider such an issue. See the Commissioner's Notice, dated September 8, 1988, 1095 O.G. 16, as clarified in his Notice, dated October 17, 1988, 1096 O.G. 196.
Accordingly, the following issues raised in the briefs are before us:
1. Whether Hoefle's claims corresponding to the count are unpatentable as urged in Suh's belated preliminary motion for judgment?
2. Whether Hoefle is not entitled to the benefit of his U.S. parent application as urged in Suh's opposition to the Hoefle preliminary motion to be accorded benefit?
3. Whether the EIC improperly denied Suh's motions to compel testimony and for additional discovery as urged in Suh's brief?
4. Whether Suh's record establishes a prior conception coupled with diligence just prior to Hoefle's entry into the field up to Suh's reduction to practice (actual or constructive)?
Suh's Belated Preliminary Motion for Judgment
On August 17, 1989, approximately 34 months after the close of the preliminary motions period, Suh filed a preliminary motion (Paper No. 177) under 37 CFR 1.633(a) for judgment urging that Hoefle's claims 1 to 4, 14 and 15 corresponding to the count are unpatentable. An opposition and a reply thereto have been filed.
Pursuant to 37 CFR 1.655(b)(3), a party in the same position as Suh is not entitled to raise for consideration at final hearing a matter which could have been properly raised by motion unless the party shows good cause why the issue was not so timely raised. Accompanying the preliminary motion is a miscellaneous motion (Paper No. 178) under 37 CFR 1.635 and § 1.646(b) wherein Suh attempts to show such good cause.
The miscellaneous motion states that the preliminary motion (Paper No. 177) could not have been filed earlier because it is based upon the testimony of the Hoefle inventors. However, the preliminary motion is not based entirely on testimony because it urges the unpatentability of Hoefle's claims because of (1) certain prior arts patents, (2) interference estoppel resulting from Hoefle's loss of a prior interference to Suh and (3) a public disclosure by Merck at a Medicinal Chemistry Symposium held at Rensselaer Polytechnic Institute on June 18, 1980. Suh states that the Hoefle inventors through their testimony admitted that it would have been obvious to one skilled in the art to combine the prior art patents in order to obtain compounds which would render obvious the Hoefle claims, even though the prior art patents provide no motivation for their combination.
*5 We agree with Hoefle that Suh has not shown good cause within the meaning of 37 CFR 1.655(b)(3) to excuse his failure to timely raise the issue of patentability by preliminary motion. In our view, Suh was aware of, or should have been aware of, the prior art patents, the interference estoppel argument and the public disclosure at the time preliminary motions were due. Thus, it appears that this belated preliminary motion was filed because of a change of opinion or purpose, which does not constitute good cause for excusing the belatedness of a motion. See 2 Rivise and Caesar, Interference Law and Practice, § 270 The Michie Co. 1943).
Prior to the expiration of the preliminary motions period, Suh had available to him experts, such as the Suh inventors, who knew of, or could have been made aware of, both the Merck public disclosure and the prior art patents. Thus, Suh was in possession of the necessary evidence to enable him to prepare affidavit(s) setting forth those matters (motivation necessary to combine these patents) which were testified to by Hoefle and which are now being relied upon by Suh to show unpatentability [FN3]. By being in possession of this evidence, Suh had no legitimate reason for not presenting it in a timely filed motion. Cf. Hanagan v. Kimura, 16 USPQ2d 1791 (Comm'r.Pat.1990); Orikasa v. Oonishi, 10 USPQ2d 1996, note 4 (Comm'r.Pat.1989).
Assuming for the sake of argument that Suh was not in possession of the necessary evidence during the preliminary motions period, we do not consider that the testimony of the Hoefle inventors concerning the development of their invention constitutes an admission of unpatentability. An admission must be clear and unmistakable. 3 Rivise and Caesar, "Interference Law and Practice", Section 402, page 1791 (The Michie Co. 1947). It is settled that an inventor's testimony as to how he developed an invention is not relevant to an obviousness analysis because the inventor may be of a higher level of skill than someone of ordinary skill in the art and what is obvious to the inventor would not necessarily have been obvious to one of ordinary skill in the art. Cf. Loctite Corp. v. Ultraseal Ltd., 781 F.2d 861, 228 USPQ 90 (Fed.Cir.1985).
For the foregoing reasons, we hold that Suh has not shown good cause within the meaning of 37 CFR 1.655(b)(3) why this preliminary motion (Paper No. 177) could not have been filed earlier. Suh's excuse that the motion is based upon testimony is not substantiated by the record. Accordingly, we will not consider the motion.
Hoefle's Entitlement to Benefit
We have carefully reviewed the arguments in the parties' briefs and we find that we agree with the EIC that Hoefle is entitled to the benefit of his U.S. parent application Serial No. 193,767, filed October 3, 1980.
*6 For a party to be accorded the benefit of a U.S. application under 35 U.S.C. 120, the application must satisfy the requirements of 35 U.S.C. 112, first paragraph, for an embodiment within the scope of the count in the special situation the count is drawn to a genus and the previously filed application discloses only a species thereof. Weil v. Fritz, 572 F.2d 856, 196 USPQ 600, note 16 (CCPA 1978).
We find that the application contains a written description for at least one species within the scope of the count. Nowhere does Suh allege otherwise. During the preliminary motions period, Suh filed an opposition (Paper No. 20) to Hoefle's preliminary motion under 37 CFR 1.633(f) for benefit of his parent U.S. application. The opposition urges that Hoefle is not entitled to the benefit of the application because the application (i) fails to "disclose or claim the compounds of Claims 5-13" of the involved Hoefle patent and (ii) contains "no written description, no enabling disclosure, nor any basis for asserting the subject matter of the claims [5 to 13]." These claims were designated as not corresponding to the count here. Clearly, these arguments did not address the question of whether Hoefle's parent application satisfies the requirements of 35 USC 112, first paragraph, so as to constitute a constructive reduction to practice of the count.
Suh's opening brief at pages 117 and 118, contends that the foregoing arguments were merely an "exemplification" and "illustrative of the deficiencies in the parent application." Then on pages 118 to 123, the brief argues for the first time that the application fails to disclose an operable method or its best mode (at the time of filing) for making a compound within the scope of the count.
We have not given these new arguments any consideration. Pursuant to 37 CFR 1.655(b)(2), Suh is not entitled to raise for consideration at final hearing a matter which properly could have been raised in an opposition to a preliminary motion. Cf. Bayles v. Elbe, 16 USPQ2d 1389 (BPAI 1990). If Suh desired to rely upon these new arguments, he should have presented them in his opposition to the motion in accordance with 37 CFR 1.638(a), which requires that the opposition shall (1) identify any material fact set forth in the motion which is in dispute and (2) include an argument why the relief requested in the motion should be denied.
For the foregoing reasons, we hold that Hoefle is entitled to the benefit of his parent application, Serial No. 193,867.
Suh's Motions to Compel and for Additional Discovery
Suh requests that we review the EIC's order of March 13, 1989 (Paper No. 141), wherein the EIC denied Suh's motions (Paper Nos. 121 to 123) to compel the testimony of the Hoefle inventors and for additional discovery.
*7 The record shows that during his assigned testimony period, Hoefle presented testimony to show conception. It is one of Suh's positions in the various papers filed before the EIC that Hoefle's conception was incomplete because Hoefle did not possess at the time thereof an operative method of making the compounds within the scope of the count.
In the order complained of, the EIC denied the motion to compel the testimony of the Hoefle inventors because the EIC found that the proposed testimony to be taken constituted an improper attack upon the senior party's entitlement to the benefit of his parent application. The EIC held that such an attack should have been presented during Suh's period for testimony-in-chief, not during his period for rebuttal testimony. In the same order, the EIC denied the motion for additional discovery as not being in the "interest of justice" (37 CFR 1.687(c)), stating that
the requested discovery has not been shown to relate to any relevant issue(s) which can be raised by Suh at final hearing. For example, Suh has not shown that Interrogatory No. 2, which is directed to the identity of the persons who "participated in the preparation" or "contributed to the preparation" of Hoefle's applications, has any relevance to the issue of whether Hoefle had conceived of an operative method for making the compounds of the count.
In its decision of April 7, 1989 (Paper No. 145) on reconsideration of the EIC's order, a panel of this Board stated:
We have reviewed the [EIC's] decision in light of the arguments raised in the request [Suh's request for reconsideration] but we are not persuaded that the EIC misapprehended or overlooked any points in rendering his decision. The testimony to be taken from Hoefle concerning the "synthetic approaches actually taken and actually resulting in the achievement of the compounds in issue" and the best mode contemplated by Hoefle for preparing the compounds at the time the Hoefle parent application was filed would not be relevant to the question of whether Hoefle possessed at the time of his alleged conception, some four months prior to the filing of the application, an operative method for preparing the compounds of the count. Whether or not the approaches subsequently utilized by Hoefle were the same as those conceived by him would not be relevant to whether Hoefle's conceived method was operative.
An interlocutory order is presumed to have been correct. The Board may consider whether an interlocutory order is manifestly erroneous or an abuse of discretion, and the burden of showing such shall be on the party attacking the order. 37 CFR 1.655(a).
We have reviewed the EIC's and the Board's orders. Contrary to the argument appearing on page 129 of Suh's opening brief, the requests accompanying the Suh motions are not "specific, relevant and material" to the Hoefle case-in-chief. Nor do they meet the established requirements at law for the reasons stated by the EIC and the Board in the aforesaid orders. Consequently, we hold that Suh has not sustained his burden to show that the orders are manifestly erroneous or an abuse of discretion.
THE PARTIES' RECORDS
*8 During his period for testimony-in-chief, Suh presented priority testimony to show a date for conception prior to Hoefle's date for conception coupled with diligence from just prior to Hoefle's date up to Suh's reduction to practice (actual or constructive). During his testimony period, Hoefle presented testimony to show a date for conception. In order to decide Suh's priority case, we must first determine Hoefle's date for conception. Accordingly, we will consider Hoefle's case first and then Suh's.
Hoefle presented an evidentiary record consisting of the testimony of nine witnesses together with 15 associated exhibits and seven cross exhibits. The testimony will be referred to as HR followed by its page number; each exhibit, as HX followed by its number; each cross exhibit, as HCX followed by its number. The witnesses testifying on behalf of Hoefle are Hoefle (also director of the cardiovascular section for chemistry) and Klutchko, the named inventors; Bennett, Blankley and Nicolaides, members of the cardiovascular group reporting to Hoefle; Kaplan, director of the cardiovascular section for biology; Capps, a research chemist sharing a lab with Nicolaides; Topliss, director of chemistry, to whom Hoefle reported; and Erickson, an expert organic chemist. The first eight witnesses were employed by or associated with Hoefle's assignee, Warner- Lambert, during the time period in question. Erickson, a professor of chemistry, testified as an expert witness.
According to the record, Warner-Lambert became interested in developing angiotensin converting enzyme (ACE) inhibitors, after the Squibb Company had developed Captopril, the first commercial ACE inhibitor. In April 1978, Warner-Lambert formed a group to develop ACE inhibitors. This group included, inter alia, Hoefle, Blankley, Bennett, and Klutchko, witnesses who testified here on behalf of Hoefle. Nicolaides, the head of the peptide group at Warner-Lambert, was later added to the ACE inhibitor group. HR 17, 29, 199 and 200.
The ACE inhibitor group was involved in three different areas of investigation, with a major focus on its research directed to modifying captopril by substituting a new group for the proline moiety thereon. Captopril [FN4] is a sulfhydryl proline terminal compound having the following structure:
TABULAR OR GRAPHIC MATERIAL SET FORTH AT THIS POINT IS NOT DISPLAYABLE
The record shows that the ACE group developed two captopril analogs which the group felt would be successful. The first (Klutchko was responsible therefor) concerned research on compounds containing a tetrahydroisoquinoline-3- carboxylic acid (THIQ) moiety having a sulfur containing side chain. HR 369. THIQ has the following structure:
The second (Blankley and Bennett were responsible therefor) concerned research with octahydroindole-2-carboxylic acid with a sulfur containing side chain. The third concerned a cooperative agreement with the Stanford Research Institute to develop ACE inhibitors which were ketomethylene analogs connected to an alanyl proline. HR 22, 23, 200, 207, 368, 369, 400 to 402 and 485 to 487.
*9 In June 1980, Hoefle, Klutchko and others in the antihypertensive group saw the program (HX 26) for the 17th National Medicinal Chemistry Symposium to be held at Rensselaer Polytechnic Institute in Troy, New York, and became aware that Merck company would make a presentation at 2:35 p.m. on June 18, 1980 concerning new developments in ACE inhibitors. The members also became aware through Dr. Kaplan that the Merck compound to be presented at the symposium would not have a sulfhydryl side chain. This caused a lot of excitement and much speculation concerning the Merck compound because the sulfhydryl side chain had been associated with unfavorable side effects. Both Hoefle and Klutchko discussed the Merck compound and speculated that if the Merck compound contained a proline moiety, they could modify the compound by replacing its proline moiety with a THIQ moiety. Bennett was aware of these speculations. Consequently, people from Warner-Lambert (Topliss, Kaplan and Lunney) and from the antihypertensive group (Bennett and Klutchko) planned to attend the meeting. Since Hoefle could not attend the meeting, he requested that Bennett telephone him after the Merck disclosure to inform him of the compound disclosed and its synthesis and activity. HR 22, 34 to 37, 205 to 207, 257 to 260, 326, 327, 371 to 373 and 400 to 402; HX 26.
On June 18, 1980, Merck disclosed at the symposium its new ACE inhibitor, designated MK-421, along with its structure, synthesis, biology and structure-activity relationship. HR 210 and 211. MK-421 [FN5] has the following structure:
TABULAR OR GRAPHIC MATERIAL SET FORTH AT THIS POINT IS NOT DISPLAYABLE
With respect to this disclosure, Klutchko testified at HR 211 and 212 as follows:
Q. What is your recollection of what the structure of MK-421 was?
A. It was a proline, an acylated proline, it was acylated with what we call a side chain, it was a non-sulfhydryl side chain.
Q. Now, as a result of the disclosure, did you have any thoughts concerning it in connection with your own work or activities?
A. Well, yes. As soon as the structure was flashed, it just came to my mind that we could probably take our tetrahydroisoquinoline-3-carboxylic acid moiety and replace the proline and probably get a very good compound.
Q. Now, you mentioned Merck disclosed something about the synthesis, what can you recall that they disclosed about the synthesis of MK-421?
Q. And what do you recall with respect to what Merck disclosed as to the activity of MK-421?
A. Well, it was a very active ACE inhibitor in vitro and in vivo and it lowered blood pressure in animals at this time, I'm pretty sure.
Q. Thank you. As a result of that, did you reach any beliefs as to whether or not the compound that you thought of, the tetrahydroisoquinoline with the MK-421 side chain, would be an active ACE inhibitor?
A. Yes, I did.
*10 After the Merck presentation and the presentation immediately following it, Klutchko, Bennett, Kaplan and Topliss left the lecture hall. Kaplan testified at HR 331 that he recollected that there was an
air of excitement of what had gone on and a recognition of the application of their [Merck's] revelation to our [Warner-Lambert's] program.
Outside the lecture hall, Klutchko discussed the presentations with Bennett and later in the evening with both Topliss and Kaplan. On both occasions, Klutchko disclosed a new compound using the Merck non-sulfhydryl side chain with a THIQ moiety. With respect to his discussion with Klutchko, Topliss testified at HR 498 that Klutchko stated that he
would use the synthetic procedure described by Merck, that these he believed would be applicable to making the tetrahydroisoquinoline-3- carboxylic acid analog and that this would--could probably be done in a month or two.
With respect to this conversation with Topliss, Klutchko testified at HR 216 that his belief that the Merck synthesis route would work with THIQ was based on the fact that
the chemistry really of tetrahydroisoquinoline-3-carboxylic acid would have similarities to a proline in that they could both be acylated similarly to get what would be equivalent to a dipeptide and then the reductive alkylation should give the final product.
HR 213 to 216, 264, 265, 331 to 335 and 496 to 498.
Thereafter, at approximately 7:00 P.M. on the evening of June 18, 1980, Bennett telephoned Hoefle per Hoefle's instructions and informed him of the disclosures made at the Merck presentation, i.e., that Merck disclosed a compound (MK-421) having a proline moiety attached to a non-sulfhydryl side chain, that the compound was formed by a reductive alkylation reaction and that the compound was as active as captopril. HR 38, 39, 266 and 267. With respect to this conversation, Bennett testified at HR 267 as follows:
Q. In that conversation, did Hoefle say anything to you?
A. As previous discussions had taken place after MERCK'S disclosure at the meeting, we had a general discussion about the possibilities of taking our two lead compounds and attaching the MERCK side chain to them.
Q. An[d] again, what were those two lead compounds?
A. The octahydroindole and the tetrahydroisoquinoline.
With respect to this conversation, Hoefle testified at HR 40 and 41 as follows:
Q. Now, after that telephone conversation on the evening of the 18th, what did you do next in connection with this?
A. I don't recall that I did anything specifically. I mean we already, you know, as soon as I knew the structure, I knew that what we wanted were the two analogs, the one octahydroindole and the other with the tetrahydroisoquinoline structures, and now there wasn't anything that could be done until I got back to the lab and could start work on it. It was immediately clear what we wanted.
On the following day, June 19, 1980, Hoefle spoke with Blankley and disclosed to him the structure of MK-421 and its similarity to captopril in ACE inhibition activity. They discussed modifying MK-421 by substituting THIQ for its proline moiety. Later in the afternoon, Hoefle spoke with Nicolaides and disclosed to him the structure of MK-421. He discussed with Nicolaides the synthesis of compounds with the new non-sulfhydryl side chain and several lead compounds and asked Nicolaides to write up a new inventive concept. HR 41 to 44, 378 to 381 and 429 to 431.
*11 Thereafter Nicolaides wrote out on pages 114 and 115 of his laboratory notebook (HX 27) the conception on behalf of Hoefle. HR 378 to 385, 424 to 429 and 444; HX 27. With respect to these discussions, Nicolaides testified at HR 426 as follows:
A. Well, I remember he was talking about putting the Merck side chain on some of their lead compound ACE inhibitors, but he only referred to the lead compounds by numbers rather than structures, and this was not uncommon. I guess I felt I knew what he was talking about at the time, that he was referring to the compounds that Syl Klutchko and Blankley and that group were engaged in looking at which would be octahydroindoles, quinolines or isoquinolines.
During his testimony, Nicolaides acknowledged that page 114 of HX 27 does not depict a THIQ analog having the Merck side chain. Concerning this he testified that he knew that the other compound of interest was either a tetrahydroquinoline (THQ) or THIQ, but after thinking about it he wrote the THQ analog at the bottom of page 114. He testified that he almost wrote down the THIQ analog but because he ran out of room at the bottom of the page, he did not want to clutter up the conception document with a lot of compounds. He thought that Hoefle wanted him to write down specific compounds, not generic structures. He also testified that the reactions routes depicted on page 115 of HX 27 are straightforward for a peptide chemist and could be utilized to make the THIQ analog with a Merck side chain. He testified that "some days or maybe a week or two" afterwards he learned that an error had been made on HX 27 by not writing down the THIQ analog and that since he was not asked to do anything about HX 27, he dropped the matter and forgot about it. HR 429 to 437; HX 27
Ericson, an expert witness, testified with respect to the reaction route described in HX 27 for making the THQ compounds described therein and its applicability for making the corresponding THIQ compounds having the Merck side chain. He testified to the effect that a skilled chemist following the reactions steps set forth in HX 27 would be able to make the THIQ counterpart of the compound described at the bottom of page 114 and went through the methology by marking up a copy of page 115 (HX 27A). Ericson testified that to understand and carry out these reactions would require a Master's degree in chemistry or a Bachelor's degree with about three years bench experience. HR 560 to 578; HX 27, 27A and 32 to 36.
Opinion re: Hoefle's conception
Before we can decide Hoefle's case for conception, we must determine whether HX 27 and 27A and all testimony associated therewith should be stricken (denied consideration) as requested in Suh's motion to suppress (Paper No. 202). The motion requests that we strike the exhibits because (i) the exhibits are outside of the scope of the count and (ii) counsel for Hoefle refused to permit counsel for Suh to inspect the "entirety of the original notebook source." The motion is denied for the reasons set forth in the Hoefle opposition (Paper No. 207).
*12 We do not consider that these arguments are well taken. In our view, HX 27 and 27A are entitled to consideration as they represent a record of Hoefle's conception. Evidence is not ordinarily stricken for alleged irrelevance which goes only to the weight to be accorded that evidence and does not constitute a basis for striking. Halbert v. Schuurs, 220 USPQ 558 (Bd.Pat.Int. 1983). Nor was Hoefle required under the rules to permit Suh's counsel to inspect the entirety of Nicolaides' notebook. Rather, Suh was only entitled to inspect originals of the exhibits relied upon and, according to Hoefle's opposition, Suh did so inspect pages 114 and 115.
We hold that the Hoefle record establishes conception on June 18, 1980.
Conception requires (1) the idea of the structure of the chemical compound, and (2) possession of an operative method of making it. Oka v. Youssefyeh, 849 F.2d 581, 7 USPQ2d 1169 (Fed.Cir.1988). The conception must be corroborated and the amount and quality of corroborative evidence is determined by a "rule of reason". Anderson v. Pieper, 442 F.2d 982, 169 USPQ 788 (CCPA 1971). Corroboration is not a ritual but a method for determining the veracity of the testimony. Corroboration can be supplied by the testimony of a witness other than the inventor. Mattor v. Coolegem, 530 F.2d 1391, 189 USPQ 201 (CCPA 1976).
We agree with Hoefle for the reasons set forth on pages 33 to 53 of his brief that his record establishes conception on June 18, 1980. Prior to the symposium, both Hoefle and Klutchko had discussed the Merck compound and speculated about its structure and possible modification with THIQ. After the Merck presentation at the symposium on June 18, 1980, Klutchko discussed with Bennett, Kaplan and Topliss a THIQ analog formed by replacing the proline moiety of MK-421 with a THIQ moiety. This constitutes a description of a compound (the THIQ analog) within the scope of the count. Klutchko discussed with Bennett, Kaplan and Topliss the preparation of the compound by using the synthetic procedure described by Merck in its preparation of MK-421. Klutchko testified that he believed that this procedure would work because of the similarity in chemistry between proline and THIQ. This establishes possession of an operative method of making the THIQ analog. Consequently, the record establishes joint conception on behalf of Hoefle and Klutchko by June 18, 1980. Bennett, Kaplan and Topliss confirmed the conversations with Klutchko thus corroborating conception and we have no reason to disbelieve their testimony. [FN6]
For the foregoing reasons, we hold that the Hoefle record establishes conception on June 18, 1980.
Suh's Case for Priority
Suh's opening brief at pages 73 and 74 urges that Suh's record establishes conception by the inventors, Suh, Barton and Regan, as early as March 26, 1979 and no later than February 27, 1980. At pages 79 to 85, the opening brief asserts that the record establishes conception on April 3, 1980, on June 18, 20 and 23, 1980, and on July 23, 1980. At page 74, the brief asserts that diligence commenced immediately after February 27, 1980 and is
*13 evidenced by the successful preparation and testing of certain necessary "lead" compounds in this new series of ACE inhibitors, i.e., fuctionalized dipeptides, containing a nonsulfhydryl acylated side chain
up to Suh's actual reduction to practice on December 4, 1980 of an ACE inhibitor, designated USV 5269.
With respect to the purported conception on March 26, 1979, Suh relies on his record at pages 36 to 39 and 157 to 163 (SR 36 to 39 and 157 to 163) and Suh exhibit (SX) 7. SX 7 depicts ten chemical structural formulas for the various proposed antihypertensive agents contained therein. According to Suh, the concept evidenced by SX 7 is directed to replacing the acylated sulfur-containing side chain of captopril with a side chain absent sulfur. The record shows that Suh assigned Skiles and Belanger to prepare a compound within the scope of SX 7, that work on this compound commenced on January 20, 1980, that the compound, L-alanyl-N-(cyclopentyl)glycine, designated as USV 3753, was prepared on February 27, 1980 and reported to have satisfactorily exhibited ACE inhibition activity. USV 3753 has the following structure:
TABULAR OR GRAPHIC MATERIAL SET FORTH AT THIS POINT IS NOT DISPLAYABLE
SR 64, 73, 81 to 87, 94 to 98, 1050, 1051, 2163 and 1264; SX 13, Rogers' Exhibit (ROG) 2 and 3, Belanger's Exhibit (BEL) 1, 2 and 4.
With respect to SX 7, Suh testified at SR 325 to 328 as follows:
Q. Would it be fair to say that based on your experience as a chemist that it [SX7] would be millions of compounds?
A. It could be.
Q. On pages 18 and 19, do you describe a chemical process for making the compounds disclosed thereon?
Q. At the time that you wrote down the disclosure on pages 18 and 19, did you extend consideration to a chemical process for making all of the compounds of compounds disclosed on pages 18 and 19?
A. Not a process.
Q. Have you since writing out the disclosure on pages 18 and 19 made an attempt to determine whether or not in fact all of the compounds encompassed by the disclosure of 18 and 19 can in fact be made?
A. No, sir.
Q. Since writing the disclosure on pages 18 and 19, have you extended any consideration to the number of different processes or processes steps that would be necessary to make all of the compounds disclosed on 18 and 19?
Q. Yes, you have given consideration to that subject?
A. Yes, sir.
Q. When did you give consideration to that?
A. I believe soon after I wrote this [sic] ideas. As I was writing this note, if I remember correctly, quite large number of compound [sic] that I conceived and expressed here can be prepared, however I also consider some of the additional literature work that required to execute some of the compounds which are difficult to prepare that may require additional literature search to select the best mode available.
Q. What, if any, specific literature did you have in mind back there in 1979?
A. My first choice is comprehensive chemical abstracts dating back from early 1900 to the present moment.
*14 With respect to the purported conception on February 27, 1980, Suh relies on his record, SR 153, 154, 163 and 164 and SX 17. SX 17 sets forth 18 chemical structures including
TABULAR OR GRAPHIC MATERIAL SET FORTH AT THIS POINT IS NOT DISPLAYABLE
a structure falling within the scope of the count. The Suh record shows that Suh assigned Berstein to prepare a compound, later designated as USV 3772, the (d) form of USV 3753, and that the synthetic preparation of USV 3772 commenced in January of 1980 and was completed by March 17, 1980. The compound was reported to have no ACE activity. Thereafter, in April of 1980 Suh assigned to Berstein the task of preparing 2-indanyl analogs of USV 3753 and 3772. As of June 23, 1980 Berstein was unable to prepare these 2-indanyl analogs. SR 1808 to 1811, 2001, 2108, 2109; Habib Exhibit (HAB) 3 and 4.
With respect to SX 17, Suh testified at HR 374 and 375 as follows:
Q. Do you have any recollection as to and now I'm limiting myself to prior to the date shown on the document, February 27, 1980, do you have any recollection of what it was that you and Regan spoke of in connection with S x 17?
A. I don't recall in detail, but we may have discussed general synthetic approaches.
Q. Do you recall what the general synthetic approaches were that you discussed?
A. Not exactly, sir.
Q. What do you recall about them generally?
A. In general regarding our target compounds and more applicable synthetic strategies that can be applied.
Q. When you say synthetic strategies that can be applied, you are referring to the methods of making these compounds that you just referred to?
A. Yes, sir.
Q. And when you refer to target compounds on S X 17, there's about three pages, roughly, containing various structural representations. Can you recall what groups of target compounds or types of target compounds the discussion with Regan had to do with?
A. To the best of my knowledge, it was more to the general method, not to any specific structures that are within the context of this Exhibit 17.
Q. In looking at Suh Exhibit 17, can we agree that the exhibit itself does not set forth any synthetic methods for the preparation of any of these types of compounds?
A. Yes. sir.
With respect to the purported conception on April 3, 1980, Suh relies upon SX 18 and Skiles Exhibit (SKI) 2 (which is the same as SX 18). SX 18 depicts 16 Group A compounds, 13 Group B compounds and 5 Group C. One of the 16 Group A compounds has the following structure:
TABULAR OR GRAPHIC MATERIAL SET FORTH AT THIS POINT IS NOT DISPLAYABLE
One of the 13 Group B compounds has the following structure:
TABULAR OR GRAPHIC MATERIAL SET FORTH AT THIS POINT IS NOT DISPLAYABLE
Concerning SKI 2, Skiles testified that it encompasses millions of compounds and that at the time he was not positive that he could make every one of the compounds described in the exhibit. SR 202, 2050 and 2051; SX 18 and SKI 2.
With respect to SX 18, Suh testified at SR 361 to 363 as follows:
Q. What specifically in S X 18 do you believe you shared with Dr. Regan?
A. I believe I probably discussed with him regarding some synthetic strategies.
*15 Q. When you say synthetic strategies, do you mean methods of preparation?
A. Yes, sir.
Q. Do you remember what specific groups of compounds that was in reference to?
A. Only in general term, N involving heterocyclic systems.
A. I do not really recall exactly but to the best of my knowledge, we may have discussed heterocyclic system that containing [sic] nitrogen.
Q. Does your understanding of S X 18 set forth any processes for the preparation of the groups of compounds contained therein?
X X X
A. No, sir.
Q. Is it your recollection that with respect to Dr. Regan you brought the structures to his attention and then you asked him questions concerning methods for synthesizing certain of them?
A. No, sir.
Q. Then would you tell me what your best recollection is as to what happened between you and Dr. Regan in that connection?
A. It is a synthetic term of preparing substituted heterocyclic dipeptides in very general term.
Q. Did you bring up the discussion or did he raise the matter with you?
A. I think I initiated it.
X X X
Q. I understand he might have made a specific suggestion. Can you be more definitive or more precise?
A. May I ask the time frame of the question?
Q. Yes. We are talking about prior to April 3, 1980.
A. I believe discussion was more in general term of synthetic approaches because it is a lot of structures but from trained chemist's eye, it is classified as substituted di, tripeptides which are reasonably well familiarized by most trained chemists who are senior level under my staff.
Opinion re: Suh's Conception
We hold that Suh's record does not establish conception prior to June 18, 1980, Hoefle's date for conception.
Conception requires (1) the idea of the structure of the chemical compound, and (2) possession of an operative method of making it. Oka v. Youssefyeh, supra.
We agree with Suh that by April 3, 1980, SX 17 and 18 show that the Suh inventors possessed amidst the millions of compounds disclosed therein the structure of tetrahydroisoqinoline compounds falling within the scope of the count in issue. However, we do not agree with Suh that his record establishes possession of an operative method of making these tetrahydroisoquinoline compounds.
With respect to the method of making the tetrahydroisoquinoline compounds of the count, it is Suh's position that having the structure of the compounds before him one skilled in the art could have made the compounds. The opening brief at pages 77 and 78 states
It is also noted that the methods employed to prepare these compounds were well recognized techniques, characterized on this record as reductive alkylation. These reactions are essentially the same methodologies later disclosed by MERCK to prepare MK-421....
*16 Further it is Suh's position at page 79 of the brief that possession of an operative method of making the compounds of the count is shown by the successful preparation of lead compounds, i.e., USV 3753 and 3772, by synthetic routes known as reductive alkylation.
We do not agree with Suh that the description in SX 17 and 18 of compounds falling within the count puts one skilled in the art in possession of a process of making them. As noted by the Court in Oka v. Youssefyeh, 7 USPQ2d at 1171,
When, as is often the case, a method of making a compound with conventional techniques is a matter of routine knowledge among those skilled in the art, a compound has been deemed to have been conceived when it was described, and the question of whether the conceiver was in possession of a method of making it is simply not raised.
In this case, the testimony of the Suh inventors shows that the method of preparing the compounds of the count is not a matter of routine knowledge, thus raising the question of whether the Suh inventors possessed at the time Suh wrote out the various structures an operative method of making the compounds of the count. The testimony of Suh and Skiles makes clear that each exhibit, SX 7, 17 and 18, describes millions of compounds [FN7] falling within different classes. Suh's testimony concerning the period of time from March 26, 1979 up to June 18, 1980, the date of Hoefle's conception, evinces no knowledge of a method of making the tetrahydroisoquinoline compounds described in these exhibits. Suh's testimony is to the effect that he "may have discussed general synthetic approaches" with others, that he does not recall those approaches in detail, that to make the compounds of these exhibits would require a number of processes or process steps and that it would require additional literature search to make some of the compounds which are difficult to prepare. Nowhere did Suh testify in the record before us that he knew a particular method of making the compounds of the count. Nor did Suh testify that he made, or had made on his behalf, any literature searches to determine such a method. Under these circumstances, we cannot presume that the structural description of the broad class of hydroisoquinolines in SX 7, 17 and 18 is sufficient to put the Suh inventors in possession of a method of making them.
Nor do we agree with Suh that the possession of an operative method of making the cyclopentyl compounds, i.e., USV 3753 and 3772, which fall within the scope of the "millions" of compounds described in SX 7, 17 and 18, shows that the Suh inventors possessed an operative method of making the hydroisoquinoline compounds described in the aforesaid exhibits. Since USV 3753 and 3772 are not compounds falling within the scope of the count, the possession of an operative method of making them does not equate to the possession of an operative method of making a compound within the scope of the count. In fact, Suh possessed no method of making a compound within the scope of the count. Further, these exhibits describe distinct classes of compounds, including the 2-indanyl compounds which are separately patentable, having been described and claimed in another application. See Oka at 1172. Also these exhibits describe numerous complex compounds, requiring various complex processes to make them. The complexity of these processes is demonstrated by the fact that at no time prior to Hoefle's conception date of June 18, 1980, did Suh possess an operable method of making the 2-indanyl compounds described in exhibits SX 7 and 17, as held by the Court in Oka v. Youssefyeh, supra, and as shown by Berstein's testimony at SR 1811. Consequently, Suh cannot rely on the successful preparation of the cyclopentyl compounds, which are outside of the count and his involved application disclosure, as showing an operable method of preparing the compounds of the count.
*17 For the foregoing reasons, we hold that Suh has not sustained his burden of proof to show conception at a date prior to Hoefle's June 18, 1980 conception date.
Assuming that the Suh record establishes conception of the subject matter of the count, which it does not, then we hold that the Suh record does not establish diligence just prior to Hoefle's entry into the field.
For diligence just prior to June 18, 1980, the Suh opening brief states at page 93
Mr. Berstein commenced preparation of this compound L-alanyl-N(2- indanyl)glycine in April of 1980 and continued these efforts through (at least) the end of June 1980. SUH R. 1808-1809. These early research efforts are reported in the June Monthly Report of Dr. Suh and Mr. Bertesin. SUH R. 1809-1811; BER EX. 1.
Citing Ginos v. Nedelec, 220 USPQ 831 (Bd.Pat.Int. 1983) and Bev v. Kollonitsch, 806 F.2d 1024, 231 USPQ 967 (Fed.Cir.1986), the brief contends that the Suh inventors may rely upon Berstein's work on the 2-indanyl and cyclopentyl derivatives. The brief recognizes that these derivatives "are not found precisely within the count of this interference" but urges that they are compounds "related in structure and intended utility and embraced by the generic concept proposed by Dr. Suh as early as February 27, 1980."
In our view, Suh cannot rely on work with respect to either the 2-indanyl or the cyclopentyl derivatives as diligence for the reduction to practice of the invention of the count because neither is within the scope of the count in issue. Under certain circumstances, a party may rely upon work on another compound outside of the scope of a count as diligence towards the reduction to practice of the count provided that the other compound is a part of the party's invention and is disclosed in the party's application. Ginos v. Nedelec, 220 USPQ 831 (Bd.Pat.Int. 1983). In this case, neither the 2-indanyl nor the cyclopentyl derivative is disclosed in Suh's involved application. Consequently, Suh's reliance upon Ginos is misplaced. Nor is Bev v. Kollonitsch, supra, apposite. Bev is concerned with attorney diligence directed to the preparation of a patent application, a different matter from diligence directed to an actual reduction to practice.
Assuming that Suh could rely on work with respect to both the 2-indanyl and the cyclopentyl derivatives as diligence towards the reduction to practice of the invention of the count, which he cannot, then Berstein's testimony does not show that Suh was diligent just prior to June 18, 1980, Hoefle's date of conception. Berstein's testimony is of a general nature and is not specific as to dates and facts. Cf. Gould v. Schawlow, 363 F.2d 908, 150 USPQ 634 (CCPA 1966); Kendall v. Searles, 173 F.2d 986, 81 USPQ 363 (CCPA 1949). In this regard, Berstein testified that "as early as March, 1980" he had "successfully prepared the compound d-alanyl-N-(cyclopentyl)glycine (USV 3772)" and confirmed its structure on March 17, 1980 by elemental analysis, that "as early as April, 1980" he commenced work on N-2-indanyl derivatives and that he was present during the period from June 17 to 20, 1980, at the symposium held at Rensselaer Polytechnic Institute where Merck made its disclosure of MK-421. SR 1808 to 1810. Nor does this testimony show any diligence just prior to Hoefle's conception date. Evidence of work taking place at least a month prior to the date of an opponent's entry into the field does not constitute diligence just prior to that date. Cf. Rieser v. Williams, 255 F.2d 419, 118 USPQ 96 (CCPA 1958). Nor would Berstein's presence during the period from June 17 to 20, 1980, at the symposium held at Rensselaer Polytechnic Institute constitute diligence towards the reduction to practice of this invention.
*18 For the foregoing reasons, we hold that Suh has not established diligence immediately just prior to Hoefle's entry into the field.
It is hereby adjudged that on the present record, Suh et al. are not entitled to a patent containing their claims 2 to 26 corresponding to the count; and
Hoefle et al. are entitled to a patent containing their claims 1 to 4, 14 and 15 corresponding to the count.
BOARD OF PATENT APPEALS AND INTERFERENCES
James A. Seidleck
Marc L. Caroff
FN1. Suh's motion is Paper No. 202; Hoefle's, Paper No. 208.
FN3. While urging that the subject matter is unpatentable to his opponent Hoefle, Suh maintains that it is patentable to him for he did not recognize any relationship between the prior art patents and the Merck disclosure. Apparently, it is Suh's position that although his inventors may not have been as perceptive as the Hoefle inventors, we should penalize Hoefle for recognizing this relationship and conversely reward Suh for not recognizing it. Suh's inconsistent position is no more than a cheap shot at an otherwise patentable invention.
FN4. We have designated the sulfhydryl side chain and the proline moiety.
FN5. We have designated the Merck side chain and the proline moiety.
FN6. It could be argued that faith should not be placed upon these witnesses' recollections because they testified as to events which had occurred some eight years earlier. Cf. D'Amico v. Tilles, 167 USPQ 176 (Bd.Pat.Int. 1969). In this case, we note that the witnesses' memories were refreshed by independent evidence, i.e., the program (HX 26) for the medicinal symposium and the general excitement at the time period of the impending Merck disclosure of a new non-sulfhydryl containing ACE compound, testified to by the inventors and the corroborating witnesses.
FN7. The Hoefle main brief at page 60 states that these exhibits encompass 400 billion compounds. The Suh reply brief at page 12 does not dispute this.