Hsing T. Huang, Appellant, v. Lee C. Cheney, Appellee, 362 F.2d 816 (C.C.P.A. 1966)

This is an appeal by junior party Huang from the decision of the Board of Patent Interferences awarding priority to senior party Cheney.¹  The sole issue here for review is priority of inventorship.

The subject matter in issue relates to a chemical composition, a synthetic penicillin realized by an acylation technique wherein 6-aminopenicillanic acid, hereafter "6-APA," is coupled with alphaphenoxypropionic acid. The single count involved reads as follows:

Count

A member selected from the group consisting of an acid of the formula

NOTE: OPINION CONTAINING TABLE OR OTHER DATA THAT IS NOT VIEWABLE

wherein R is (lower) alkyl and its sodium salt and its potassium salt.

The record shows that both parties began their research after reading an article by Batchelor et al.²  The article disclosed a fermentation process for preparing 6-APA and disclosed that 6-APA was a most useful chemical intermediate for the preparation of new penicillins.

As the board stated in its opinion:

Both Cheney and Huang appeared to react promptly to this almost express invitation to prepare new penicillins. * * *

The record shows that each party eventually realized a product within the count by utilizing acids selected from a large list prepared for reaction with 6-APA.

The record shows that Cheney's list of acids was prepared by April 1, 1959. A product within the count was prepared April 21, 1959, and his patent application was filed May 25, 1959. The record shows that Huang's list of acids was prepared sometime in May, 1959. A product within the count was prepared July 10, 1959, and his application was filed September 28, 1959.

Appellant Huang, in attempting to show error in the decision of the board, presents three arguments:

1. Huang conceived the invention of the interference count prior to the filing date of the Cheney application and worked diligently from at least that date until his own reduction to practice of the invention.

2. Cheney proved no conception at any time of the invention of the interference count and no actual reduction to practice of the invention prior to the filing date of the application bearing his name.

3. The filing of the application Serial No. 815,287 cannot be relied on by Cheney as a constructive reduction to practice of the invention of the interference count.

We will consider the above arguments in the order stated.

The earliest date advanced by Huang as to activity concerning the invention is February 25, 1959. Appellant's brief states, "Huang testified that he disclosed the invention of the interference count to Finlay [Huang's superior] on or about February 25, 1959." Huang testified as follows:

And Mr. Finlay and I had a discussion on February the 25th on the general nature of the type of penicillins that could be synthesized from 6-aminopenicillanic acid, which might prove to be useful. I indicated to him that by the use of 6-aminopenicillanic acid, it would be possible to make new penicillins with a substituent in the alpha position.

* * * * * *

We were, of course, aware of the fact that penicillin V was a useful oral penicillin on the market, well established for many years, and we were also aware of the fact that what we call penicillin S — that would be the sulfur analog of penicillin V, phenylmercaptoethyl penicillin, was also a potentially useful oral penicillin. So the thought occurred to me that if we put an alkyl group in the alpha position we might produce some useful properties.

However, without going into specific cases, since we thought that at that time our knowledge on the subject was by no means extensive, I wrote up a memo to Mr. Finlay in which I summarized the idea in a rather general form.

The memo referred to by Huang, dated February 27, 1959, was introduced as evidence and it states, in pertinent part, as follows:

During our discussion on 2/25/59, I made the suggestion that the attachment of one or more additional substituents, particularly bulky groups, on the side chain methylene (-CH₂-) function, as in (III), might effectively hinder the approach of the enzymatic site

NOTE: OPINION CONTAINING TABLE OR OTHER DATA THAT IS NOT VIEWABLE

to the reactive portion of the molecule, and hence render the new penicillin much less susceptible to penicillinase inactivation. Such a penicillin will be of great interest clinically, if its antibiotic activity would remain unimpaired.

Huang testified, concerning the memo, as follows:

Q31. Now, Dr. Huang, referring to this February 27 memo, will you tell us where on there you find the subject matter relating to the count of this interference? A. Well, it could be included in formula 3, putting in the right type of substituent for R₁, R₂, and R₃.

Q23. What would those substituents be, for instance? A. For instance if R₁ is hydrogen, R₂ could be phenoxy, and R₃ could be an alkyl group.

Witness Finlay also testified as to the memo as follows:

Q13. Can you tell me if you find on that memo the subject matter of this particular interference, either specifically or generally? A. You mean the structural formula here? The structural formula here, R₃ is hydrogen; R₁ would be phenoxyacetone; R₂ would be the methyl group or substituted various alkyl groups.

Miss Sturtevant: May the record show the witness is referring to the formula III, a little below the middle of page 1 of the memo.

Q14. Do you remember any more specific reference to the subject matter of this interference? A. The background of our work in this area? Is that what you refer to, why we were working in this area?

Q15. Yes, during this period, February 1959 onward, do you remember any reference specifically to the subject matter of the interference as opposed to, for instance, the generic formula III, to which you have referred? A. Dr. Huang and I had numerous discussions. He refers here, I believe, to one of the discussions — "During our discussion of 2/25/59" — and that was one of a great number of discussions of the same type, and because of our background work in this area, the phenoxyethyl and other alkyl penicillins of this type were of great interest to us, and it goes back to our work of attempting biosynthesis on compounds of this sort.

* * * * * *

Q16. Do you remember when you received this specific reference to the compounds of this interference count, the phenoxyethyl and lower-alkyl penicillins from Dr. Huang? A. I can date it to some extent by the fact that I went to Japan in late April 1959, and it was certainly before then. I was in Japan for six weeks, during May and the first two weeks of June, in Japan and other countries in the Orient, so it was before I went, because cause certainly the work had been accomplished by the time I got back.

Q17. When did you leave for Japan? A. I believe it worked out the date is April 29. So that would indicate that it was before that that Dr. Huang divulged to me his plans for making compounds of this type synthetically from 6-APA, before April 28, which was the last day that I was at work.

A second memo, dated May 12, 1959, was also introduced on behalf of Huang. The pertinent portions of the memo are as follows:

This report outlines the current program carried out in Lab. 811 and Lab. 812 on the preparation and testing of new penicillins from penicin. The basic ideas involved have been discussed previously, at one time or another, with you and Dr. Weber or Mr. Finlay. For convenience, penicin will be referred to as NH₂-P-CO₂H, where P stands for the β-lactamthiazolidine nucleus of penicillin, i. e.

NOTE: OPINION CONTAINING TABLE OR OTHER DATA THAT IS NOT VIEWABLE

New penicillins formed in solution are tested without purification for a) position on papergram, b) acid stability and in selected cases, c) susceptibility to penicillinase. They are then examined by Dr. English for activity against S. aureus, E. coli, S. typhosa, and a penicillinase-producing, penicillin resistant strain of S. aureus (No. 376). The aim is to screen rapidly as wide a variety of new penicillins as possible so that data on the type of side chain which would confer a specific, desired property can be quickly accumulated. Among the classes of side chains which we have coupled on to penicin or expect to work on are the following:

1. Di- and tri- substituted acetyl, R₁ R₂ CHCO- and R₁ R₂ R₃ C-CO, where R₁, R₂ and R₃ can be alkyl, aryl halogen, alkyloxy, aryloxy, alkylthio, arylthio, etc.

 Examples: diphenylacetyl (C6H5)2CHCO-, dichloroacetyl, C12CHCO-, α-methylphenylthioacetyl, C6H5SCHMeCO-.

Huang testified, concerning the memo, as follows:

You will note in that memo I describe briefly the aims of our experiments, and the different types of penicillins that we thought could be made from 6-APA. I direct your attention to item I on page 1.

Q40. This is Roman numeral I and Arabic 1? A. Yes, Roman numeral I and Arabic 1, in which I gave examples of different types of substituents that could be placed on the methylene group on the alpha carbon of a penicillin. And I mention here aryl oxy and alkyl as possible substituents for R₁, R₂, or R₃, or for R₁ and R₂ in the first general formula for the side chain, that is R₁ R₂ CHCO.

Miss Sturtevant: May the record show that by the "first general formula," Dr. Huang means the formula in the first line of Arabic 1 of page 1 of this memo, the disubstituted acetyl.

Q41. Do you find anything else in that section of the memo, Dr. Huang, which is closely related to the subject matter of this interference? A. Well, you will note in the examples under item Arabic 1, I gave alpha-ethylphenyl-thioacetyl, C₆H₅SCHMeCO, which is, of course, the sulfur analog of the subject penicillin then under discussion.

* * * * * *

Q46. Dr. Huang, between the February 25, 1959 discussion with Mr. Finlay and the May 12, 1959 memo, did you do any other work on this project of making the so-called synthetic penicillins? A. Up to May 2, the work was carried out more or less on an exploratory basis. We did not have a special approval from management, since there was no assurance that we would be able to obtain sufficient amounts of 6-APA for these experiments, and also there was no assurance that we could be able to manufacture 6-APA at all. It was obvious that Beecham Laboratories had the knowhow of making 6-APA and at that time we certainly did not. So we spent our time, first, in trying to obtain some 6-APA, pure 6-APA for preliminary experiments.

It is clear at this time, notwithstanding Finlay's testimony, that Huang did not testify as to any personal conception of specific compounds within the count. Huang testified as to the possibilities concerning what his counsel termed "generic formula III" in the memo of February 27, 1959. Also, the record shows that the initial work by Huang was directed to obtaining 6-APA. By the "middle of May" a process had been realized wherein large quantities of 6-APA could be obtained. According to Huang, "this, naturally, changed our whole outlook on the problem."

The next activity is described in the testimony as follows:

Q148. When did you begin the mass, large scale reactions with the newly found 6-APA to prepare a variety of acylated derivatives? A. Well, our research directors actually initiated this idea of mass screening of a large number of organic acids. Inasmuch as very little was known about the effect of structural activity they thought the fastest way to get some information was to run through a very large number of organic acids, couple them with 6-APA, run through primary tests against selected numbers of bacteria, and see what kind of results we would get. And this program was initiated after we had assurance that there was going to be a steady supply of 6-APA.

It was organized somewhere in the middle of May, or towards the latter part of May.

According to the testimony, Dr. Seto was instructed to prepare a list of organic acids and Huang, by a memo dated May 27, 1959, initiated a mass screening program. Twenty seven acid reactants available to Pfizer were initially used. Huang testified:

Q164. Do you find anywhere in those 27 acids a reactant to prepare a compound or compounds closely related to the compounds of the interference count here? A. Well, for instance, on page 152, sample No. 19 involves the coupling of alpha-2, 4 dichlorophenoxy propionic acid with 6-APA. And this compound, of course, is just the 2,4 dichloro derivative of phenoxy propionic acid, which would be the precursor for the penicillin involved in the interference count.

Concerning the list prepared by Dr. Seto setting forth over 400 compounds, which was "finished by the end of May," Huang testified as follows:

Q172. I direct your attention to page 12 of this list and ask you if you find on that page any acid reactant which would produce a compound related to one of the compounds of this interference. A. Yes, about two-thirds down on page 12 you will note item No. 5378-P, alpha-phenoxypropionic acid. That was ordered from Fisher. * * *

* * * * * *

Q174. What compound would result from the acylation of 6-APA with that? A. This would give rise to alpha-phenoxyethyl penicillin.

* * * * * *

Q176. This would be one of the compounds of the interference count, then, is that correct? A. Yes.

The record shows that the acid referred to above was not received. Huang testified he "was particularly interested in it" and he took steps, on July 8, 1959, to secure some from another source. On July 10, 1959, a compound was prepared within the count. By July 22, 1959, it had been concluded that the compound had good activity. Testing on humans was concluded on September 3, 1959, with favorable results.

We have set forth appellant's evidence as to conception and diligence in substantial detail. We find it, however, insufficient to establish conception prior to appellee's filing date. Its chief fault lies in its lack of specificity as to compounds within the count.

It is clear that Huang's testimony does not set forth a disclosure of the invention in the memo to Finlay, dated February 27, 1959. Huang chose to testify only that it "could be included in formula 3, putting in the right type of substituent for R₁, R₂, and R₃." We note that the suggested substitutions in the memo are different from the substitutions required in the count. Similarly, concerning the memo of May 12, 1959, Huang mentioned "aryl oxy and alkyl as possible substituents," and he testified as to the sulfur analog of the penicillin defined by the count. The memo of May 27, 1959, establishes only that a "precursor for the penicillin involved in the interference count" was tested and Huang testified only as to that fact. This is two days after Cheney's filing date.

The first testimony of Huang as to an interest in an acid from which a specific compound within the count could be prepared concerns No. 5378 P on page 12 of the list prepared by Dr. Seto at the end of May. There is no testimony establishing when this interest occurred.

The board summarized the evidence on behalf of Huang as follows:

The evidence adduced in behalf of Huang fails to establish conception of any species within the count, or any intention to make such species prior to the constructive reduction to practice of Cheney on May 25, 1959.

We agree with the board's conclusions. Huang's testimony and the evidence introduced does not support counsel's statements that Huang disclosed the invention to Finlay. As Huang did not disclose or testify to a conception of the invention prior to Cheney's filing date, Finlay's testimony cannot serve as a corroboration.

Appellant's second and third arguments are directed to proving that Cheney has not proven a conception and reduction to practice, either actual or constructive. The gist of these arguments is that Cheney did not participate sufficiently in the research program which resulted in the claimed subject matter. It is clear from appellant's brief that these arguments are directed to showing someone else and not Cheney is legally responsible for conception and reduction to practice. The question of third party inventorship may not be raised in an interference proceeding. See, e. g., Mortsell v. Laurila, 301 F.2d 947, 49 CCPA 1028.

For the above reasons the decision of the board is affirmed.

Affirmed.

MARTIN, J., did not participate in the consideration or decision of this case.