Board of Patent Appeals and Interferences
Patent and Trademark Office (P.T.O.)
*1 EX PARTE RONALD A. HITZEMAN AND JOHN A. CARBON
Appeal No. 86-1753
September 17, 1987
Application for Patent filed August 19, 1983, Serial No. 525,257, which is a Continuation of Serial No. 333,341, filed December 22, 1981. Novel Eukaryotic Vectors and Plasmids Having PGK Regulatory Signals.
Bertram I. Rowland et al. for Appellants
Alvin E, Tanenholtz
Before Pellman, Winters and Caroff
Appeal from the examiner's decision refusing to allow claims 1 through 10 and 12 through 14, which are all of the claims in this application.
Claims 1, 6, 8, 9 and 12 are representative:
1. A novel eukaryotic vector comprising a eukaryotic extrachromosomal replication system and the regulatory signals for expression of the PGK gene having a restriction site intermediate the promoter and terminator of said yeast PGK gene.
6. A vector useful for expression of a structural gene in yeast comprising the 2 u-replication system, a chromosomal replicator, the regulatory genes of the yeast PGK gene and having a restriction site intermediate the promoter and terminator of said PGK regulatory genes.
8. A vector according to any of Claims 6 or 7, having a structural gene inserted into said restriction site, with expression of said structural gene being under the regulatory control of said regulatory signals of said PGK gene.
12. A method of producing a peptide which comprises growing a transformant according to Claim 9 in an appropriate nutrient medium under conditions whereby said structural gene is expressed to produce said peptide; and isolating said peptide.
The examiner does not rely on any prior art references.
References of record cited and relied on by the appellants are:
Mellor et al. (Mellor), "Gene", Vol. 24, pages 1-14 (1983)
Derynck et al. (Derynck), "Experimental Manipulation of Gene Expression", Edited by Inouye, Academic Press, pages 247-258, (1983)
Hitzeman et al. (Hitzeman), Science, "Secretion of Human Inteferons By Yeast", Vol. 219, pages 620-625, (February 11, 1983)
Hitzeman et al. (Hitzeman), "Recombinant DNA Products: Insulin, Interferon and Growth Hormone" edited by Bollon, CRC Press, pages 47-64 (January 1985)
Singh et al., (Singh) "Genetics: New Frontiers, Oxford and IBH Publishing Co.", pages 167-177 (1983).
Chen et al., (Chen) "Nucleic Acids Research", Vol. 12, No. 23, pages 8951-8970, (1984)
The issue presented for review is whether the examiner correctly rejected claims 1 through 10 and 12 through 14 under 35 USC 112, first paragraph as based on a non-enabling disclosure.
We shall sustain this rejection.
Having carefully reviewed the rejection in light of appellants' argument, we find ourselves in essential agreement with the points and reasoning stated by the examiner in his Answer. In our view, the scope of enablement provided to one having ordinary skill in the art by appellants' specification disclosure is not commensurate with the scope of protection sought by the appealed claims. In re Moore, 439 F.2d 1232, 169 USPQ 236 (CCPA 1971).
*2 We are mindful that it is incumbent on the PTO, whenever a rejection on this basis is made, to advance acceptable reasoning or evidence which is inconsistent with enablement. That is, it is incumbent on the examiner to first establish a prima facie case of non-enablement. In re Armbruster, 512 F.2d 676, 185 USPQ 152 (CCPA 1975); In re Marzocchi, 439 F.2d 220, 169 USPQ 367 (CCPA 1971). The examiner has done just that here. Basing his position on sound scientific reasoning, the examiner points out in his Answer that:
(1) the broad term "yeast" used in the appealed claims includes a number of diverse fungi which are quite different, morphologically and biochemically, from Saccharomyces cerivisae;
(3) this case involves highly unpredictable factors including unique, delicate, and unpredictable biochemical and genetic actions;
(4) although highly unpredictable factors are involved, nonetheless, appellants' disclosure merely sets forth a "generalized protocol" or "general recipe" without providing essential details for preparing vectors or yeast transformants within the scope of the appealed claims;
(5) appellants' disclosure would enable "the preparation of a Saccharomyces cerivisae DNA vector containing the 2 micron yeast replicating system and the 3.1 kbp hind III PGK gene fragment including its promoter sequences wherein the PGK structural gene possesses a restriction site" (Answer, page 3), but the appealed claims are not so limited; and
(6) appellants' disclosure constitutes an invitation to experiment, that is, the disclosure "presents enormous workloads that would require undue experimentation to find other operative eukaryotic extrachomosomal replication systems and PGK genes. and it would require knowledge far beyond that presently possessed." See the Examiner's Answer, page 4.
Further with respect to the prima facie case of nonenablement, we note that a single embodiment may provide broad enablement in cases involving predictable factors, such as mechanical or electrical elements. In cases involving unpredictable factors, such as most chemical reactions and physiological activity, more is required. In re Fisher, 427 F.2d 833, 166 USPQ 18 (CCPA 1970). Here, appellants' specification fails to provide those having ordinary skill in the art reasonable assurance, as by adequate representative examples, that vectors and yeast transformants falling within the scope of the appealed claims can be prepared and used. See In re Surrey, 370 F.2d 349, 151 USPQ 724 (CCPA 1966). [FN1]
Appellants rely on the Carbon declaration, filed June 27, 1983, and on the six prior art references cited supra in an effort to rebut the examiner's prima facie case of non-enablement. In our view, that reliance is misplaced.
*3 As pointed out by the examiner, the Carbon declaration relates to a procedure for preparing a DNA vector wherein the PGK gene bearing the PGK promoter was fused to a beta galactosidase gene. That construction is different from what is disclosed in appellants' specification and the procedures for its preparation are substantially different. Therefore, as stated by the examiner, "rather than supporting appellants' position the Carbon affidavit militates against it". See the Examiner's Answer, page 6.
With respect to the cited prior art publications, the examiner correctly found that these publications use different techniques from those set forth by appellants and/or indicate the necessity of using additional procedures. See the Examiner's Answer, page 6. Appellants' position to the contrary notwithstanding, the cited publications thus indicate that appellants' specification is non-enabling.
In any event, as pointed out by the examiner, each of the cited publications was published after the effective filing date of this application. That being the case, the holding in In re Glass, 492 F.2d 1228, 181 USPQ 31, 34 (CCPA 1974) is directly applicable to the facts of this case, namely,
[W]e now rule that application sufficiency under § 112, first paragraph, must be judged as of its filing date. It is an applicant's obligation to supply enabling disclosure without reliance on what others may publish after he has filed an application on what is supposed to be a completed invention and
later issuing patents or publications may not be relied upon to establish that the specification is enabling under § 112, paragraph one.
In view of that holding, appellants' reliance is misplaced, namely, their reliance on publications published after the effective filing date to rebut a prima facie case of non-enablement. [FN2]
Finally, we note that claim 14 in this application was added to the case in an Amendment filed July 12, 1985 (Paper No. 16). In the Amendment appellants indicated that "[t]his claim finds support in the Specification at page 3, lines 6 ff". See Paper No. 16, page 2. However, we have reviewed the entire specification, including page 3, and find no descriptive support therein for the subject matter now defined in claim 14. Nor do we find in the specification any clear and precise defintion of the terms "the leader region" and "a unique restriction site", which terms are recited in the appealed claims. In view of our disposition of this case, however, we shall not enter a new ground of rejection based on the foregoing points.
For the reasons presented above and those well stated by the examiner in his Answer, we sustain the examiner's rejection. The examiner's decision refusing to allow claims 1 through 10 and 12 through 14 is affirmed.
BOARD OF PATENT APPEALS and INTERFERENCES
Irving R. Pellman
Sherman D. Winters
FN1. We agree with appellants that working examples are desirable but not required in all cases to satisfy section 112, first paragraph. In re Strahilevitz, 668 F.2d 1229, 212 USPQ 61 (CCPA 1982). The question is whether appellants' specification, considered in its entirety, provides a scope of enablement commensurate with the scope of protection sought by the appealed claims. On the facts presented, we find that appellants' specification does not.
FN2. In Glass, the appellant attempted to use disclosures of four patents which issued after his filing date to "supplement" the specification. Here, appellants urge that later-published publications "substantiate" enablement by showing successful work of researchers "substantially following applicants' procedures". See the Brief, page 7. Regardless of the different complexion of the arguments presented, we find that the holding of Glass is controlling on the facts of this case.