947 F.2d 488 | Fed. Cir. | 1991
Lead Opinion
This appeal is from the September 12, 1990 decision of the Patent and Trademark Office (PTO) Board of Patent Appeals and Interferences (Board), affirming the examiner’s rejection of claims 1-48 and 50-52 of application Serial No. 07/021,405, filed March 4, 1987, titled “Hybrid Genes Incorporating a DNA Fragment Containing a Gene Coding for an Insecticidal Protein, Plasmids, Transformed Cyanobacteria Expressing Such Protein and Method for Use as a Biocontrol Agent” as unpatentable under 35 U.S.C. § 103, as well as the rejection of claims 1-48 and 50-51 under 35 U.S.C. § 112, first paragraph, for lack of enablement. We reverse the § 103 rejection. The § 112 rejection is affirmed in part and reversed in part.
BACKGROUND
A. The Invention
The claimed invention is directed to the use of genetic engineering techniques
As described by appellants, the claimed subject matter meets this need by providing for the production of the insecticidal Bacillus proteins within host cyanobacte-ria. Although both cyanobacteria and bacteria are members of the procaryote
More particularly, the subject matter of the application on appeal includes a chimeric (i.e., hybrid) gene comprising (1) a gene derived from a bacterium of the Bacillus genus whose product is an insecticidal protein, united with (2) a DNA promoter effective for expressing
The claims on appeal are 1-48 and 50-52, all claims remaining in the application. Claim 1 reads:
1. A chimeric gene capable of being expressed in Cyanobacteria cells comprising:
(a) a DNA fragment comprising a promoter region which is effective for expression of a DNA fragment in a Cyano-bacterium; and
(b) at least one DNA fragment coding for an insecticidally active protein produced by a Bacillus strain, or coding for an insecticidally active truncated form of the above protein or coding for a protein having substantial sequence homology to the active protein,
the DNA fragments being linked so that the gene is expressed.
Claims 2-15, which depend from claim 1, recite preferred Bacillus species, promoters, and selectable markers.
B. Appellants’ Disclosure
In addition to describing the claimed invention in generic terms, appellants’ specification discloses two particular species of Bacillus (B. thuringiensis, B. sphaericus) as sources of insecticidal protein; and nine genera of cyanobacteria (Synechocystis, Anacystis, Synechococcus, Agmenellum, Aphanocapsa, Gloecapsa, Nostoc, Ana-baena and Ffremyllia) as useful hosts.
The working examples relevant to the claims on appeal detail the transformation of a single strain of cyanobacteria, i.e., Synechocystis 6803. In one example, Sy-nechocystis 6803 cells are transformed with a plasmid comprising (1) a gene encoding a particular insecticidal protein (“B.t. 8”) from Bacillus thuringiensis var. israe-lensis, linked to (2) a particular promoter, the Pl promoter from the bacteriophage Lambda (a virus of E. coli). In another example, a different promoter, i.e., the Sy-nechocystis 6803 promoter for the rubisco operon, is utilized instead of the Lambda Pl promoter.
C. The Prior Art
A total of eleven prior art references were cited and applied, in various combinations, against the claims on appeal.
The focus of Dzelzkalns,
Sekar I,
Friedberg
Miller
Nierzwicki-Bauer
Chauvat
Reiss
Kolowsky
Barnes, United States Patent No. 4,695,-455, is directed to the treatment with stabilizing chemical reagents of pesticides produced by expression of heterologous genes (such-as those encoding Bacillus proteins) in host microbial cells such as Pseudomo-nas bacteria. The host cells are killed by this treatment, but the resulting pesticidal compositions exhibit prolonged toxic activity when exposed to the environment of target pests.
1. The § 103 Rejections
Claims 1-6, 16-21, 33-38, 47-48 and 52 (which include all independent claims in the application) were rejected as unpatentable under 35 U.S.C. § 103 based upon Dzelzkalns in view of Sekar I or Sekar II and Ganesan. The examiner stated that Dzelzkalns discloses a chimeric gene capable of being highly expressed in a cyano-bacterium, said gene comprising a promoter region effective for expression in a cya-nobacterium operably linked to a structural gene encoding CAT. The examiner acknowledged that the chimeric gene and transformed host of Dzelzkalns differ from the claimed invention in that the former’s structural gene encodes CAT rather than insecticidally active protein. However, the examiner pointed out, Sekar I, Sekar II, and Ganesan teach genes encoding insecti-cidally active proteins produced by Bacillus, and the advantages of expressing such genes in heterologous
Additional rejections were entered against various groups of dependent claims which we need not address here. All additional rejections were made in view of Dzelzkalns in combination with Sekar I, Sekar II, and Ganesan, and further in view of other references discussed in Part C above.
The Board affirmed the § 103 rejections, basically adopting the examiner's Answer as its opinion while adding a few comments. The legal conclusion of obviousness does not require absolute certainty, the Board added, but only a reasonable expectation of success, citing In re O’Farrell, 853 F.2d 894, 7 U.S.P.Q.2d 1673 (Fed. Cir.1988). In view of the disclosures of the prior art, the Board concluded, one of ordinary skill in the art would have been motivated by a reasonable expectation of success to make the substitution suggested by the examiner.
2. The § 112 Rejection
The examiner also rejected claims 1-48 and 50-51 under 35 U.S.C. § 112, first paragraph, on the ground that the disclosure was enabling only for claims limited in accordance with the specification as filed. Citing Manual of Patent Examining Procedure (MPEP) provisions 706.03(n)
[t]he cyanobacteria comprise a large and diverse group of photosynthetic bacteria including large numbers of species in some 150 different genera including Synechocystis, Anacystis, Synechococ-cus, Agmenellum, Nostoc, Anabaena, etc. The molecular biology of these organisms has only recently become the subject of intensive investigation and this work is limited to a few genera. Therefore the level of unpredictability regarding heterologous gene expression in this large, diverse and relatively poorly studied group of procaryotes is high....
The Board affirmed, noting that “the limited guidance in the specification, considered in light of the relatively high degree of unpredictability in this particular art, would not have enabled one having ordinary skill in the art to practice the broad scope of the claimed invention without undue experimentation. In re Fisher, 427 F.2d 833, 166 U.S.P.Q. 18 (CCPA 1970).”
OPINION
A. Obviousness
We first address whether the PTO erred in rejecting the claims on appeal as prima facie obvious within the meaning of 35 U.S.C. § 103. Obviousness is a legal question which this court independently reviews, though based upon underlying factual findings which we review under the clearly erroneous standard. In re Woodruff, 919 F.2d 1575, 1577, 16 U.S.P.Q.2d 1934, 1935 (Fed.Cir.1990).
Where claimed subject matter has been rejected as obvious in view of a combination of prior art references, a proper analysis under § 103 requires, inter alia, consideration of two factors: (1) whether the prior art would have suggested to those of ordinary skill in the art that they should make the claimed composition or device, or carry out the claimed process; and (2) whether the prior art would also have revealed that in so making or carrying out, those of ordinary skill would have a reasonable expectation of success. See In re Dow Chemical Co., 837 F.2d 469, 473, 5 U.S.P.Q.2d 1529, 1531 (Fed.Cir.1988). Both the suggestion and the reasonable expectation of success must be founded in the prior art, not in the applicant’s disclosure. Id.
We agree with appellants that the PTO has not established the prima facie obviousness of the claimed subject matter. The prior art simply does not disclose or suggest the expression in cyanobacteria of a chimeric gene encoding an insecticidally active protein, or convey to those of ordinary skill a reasonable expectation of success in doing so. More particularly, there is no suggestion in Dzelzkalns, the primary reference cited against all claims, of substituting in the disclosed plasmid a structural gene encoding Bacillus insecticidal proteins for the CAT gene utilized for selection purposes. The expression of antibiotic resistance-conferring genes in cyanobacte-ria, without more, does not render obvious the expression of unrelated genes in cyano-bacteria for unrelated purposes.
The PTO argues that the substitution of insecticidal Bacillus genes for CAT marker genes in cyanobacteria is suggested by the secondary references Sekar I, Sekar II, and Ganesan, which collectively disclose expression of genes encoding Bacillus insecticidal proteins in two species of host Bacillus bacteria (B. megaterium and B. subtilis) as well as in the bacterium E. coli. While these references disclose expression of Bacillus genes encoding insecticidal proteins in certain transformed bacterial hosts, nowhere do these references disclose or suggest expression of such genes in transformed cyanobacterial hosts.
To remedy this deficiency, the PTO emphasizes similarity between bacteria and cyanobacteria, namely, that these are both procaryotic organisms, and argues that this fact would suggest to those of ordinary skill the use of cyanobacteria as hosts for expression of the claimed chimeric genes. While it is true that bacteria and cyano-bacteria are now both classified as procar-yotes, that fact alone is not sufficient to motivate the art worker as the PTO con
At oral argument the PTO referred to additional secondary references, not cited against any independent claim (i.e., Fried-berg, Miller, and Nierzwicki-Bauer), which it contended disclose certain amino acid sequence homology between bacteria and cyanobacteria. The PTO argued that such homology is a further suggestion to one of ordinary skill to attempt the claimed invention. We disagree. As with the Dzelzkalns, Sekar I, Sekar II, and Ganesan references discussed above, none of these additional references disclose or suggest that cyanobacteria could serve as hosts for expression of genes encoding Bacillus insecticidal proteins. In fact, these additional references suggest as much about differences between cyanobacteria and bacteria as they do about similarities. For example, Nierzwicki-Bauer reports that a certain nucleotide sequence (i.e., the -10 consensus sequence) in a particular cyano-bacterium resembles an E. coli promoter, but that another nearby nucleotide sequence (the -35 region) does not. While Miller speaks of certain promoters of the bacteriophage Lambda that are recognized by both cyanobacterial and E. coli RNA polymerases, it also discloses that these promoters exhibited differing strengths when exposed to the different polymerases. Differing sensitivities of the respective polymerases to an inhibitor are also disclosed, suggesting differences in the structures of the initiation complexes.
The PTO asks us to agree that the prior art would lead those of ordinary skill to conclude that cyanobacteria are attractive hosts for expression of any and all hetero-logous genes. Again, we can not. The relevant prior art does indicate that cyano-bacteria are attractive hosts for expression of both native and heterologous genes involved in photosynthesis (not surprisingly, for the capability of undergoing oxygenic photosynthesis is what makes the cyano-bacteria unique among procaryotes). However, these references do not suggest that cyanobacteria would be equally attractive hosts for expression of unrelated heterolo-gous genes, such as the claimed genes encoding Bacillus insecticidal proteins.
In O’Farrell, this court affirmed an obviousness rejection of a claim to a method for producing a “predetermined protein in a stable form” in a transformed bacterial host. 853 F.2d at 895, 7 U.S.P.Q.2d at 1674. The cited references included a prior art publication (the Polisky reference) whose three authors included two of the three coinventor-appellants. The main difference between the prior art and the claim at issue was that in Polisky, the heterolo-gous gene was a gene for ribosomal RNA, while the claimed invention substituted a gene coding for a predetermined protein. Id. at 901, 7 U.S.P.Q.2d at 1679. Although, as the appellants therein pointed out, the ribosomal RNA gene is not normally translated into protein, Polisky mentioned preliminary evidence that the transcript of 'the ribosomal RNA gene was translated into protein, and further predicted that if a gene coding for a protein were to be substituted, extensive translation might result. Id. We thus affirmed, explaining that
the prior art explicitly suggested the substitution that is the difference between the claimed invention and the prior art, and presented preliminary evidence suggesting that the [claimed] method could be used to make proteins.
*495 ... Polisky contained detailed enabling methodology for practicing the claimed invention, a suggestion to modify the prior art to practice the claimed invention, and evidence suggesting that it would be successful.
Id. at 901-02, 7 U.S.P.Q.2d at 1679-80.
In contrast with the situation in O’Farrell, the prior art in this case offers no suggestion, explicit or implicit, of the substitution that is the difference between the claimed invention and the prior art. Moreover, the “reasonable expectation of success” that was present in O’Farrell is not present here. Accordingly, we reverse the § 103 rejections.
B. Enablement
The first paragraph of 35 U.S.C. § 112 requires, inter alia, that the specification of a patent enable any person skilled in the art to which it pertains to make and use the claimed invention. Although the statute does not say so, enablement requires that the specification teach those in the art to make and use the invention without “undue experimentation.” In re Wands, 858 F.2d 731, 737, 8 U.S.P.Q.2d 1400, 1404 (Fed.Cir.1988). That some experimentation may be required is not fatal; the issue is whether the amount of experimentation required is “undue.” Id. at 736-37, 8 U.S.P.Q.2d at 1404. Enablement, like obviousness, is a question of law which we independently review, although based upon underlying factual findings which we review for clear error. See id. at 735, 8 U.S.P.Q.2d at 1402.
In response to the § 112 rejection, appellants assert that their invention is “pioneering,” and that this should entitle them to claims of broad scope. Narrower claims would provide no real protection, appellants argue, because the level of skill in this art is so high, art workers could easily avoid the claims. Given the disclosure in their specification, appellants contend that any skilled microbiologist could construct vectors and transform many different cyano-bacteria, using a variety of promoters and Bacillus DNA, and could easily determine whether or not the active Bacillus protein was successfully expressed by the cyano-bacteria.
The PTO made no finding on whether the claimed invention is indeed “pioneering,” and we need not address the issue here. With the exception of claims 47 and 48, the claims rejected under § 112 are not limited to any particular genus or species of cyano-bacteria. The PTO’s position is that the cyanobacteria are a diverse and relatively poorly studied group of organisms, comprising some 150 different genera, and that heterologous gene expression in cyano-bacteria is “unpredictable.” Appellants have not effectively disputed these assertions. Moreover, we note that only one particular species of cyanobacteria is employed in the working examples of appellants’ specification, and only nine genera of cyanobacteria are mentioned in the entire document.
Taking into account the relatively incomplete understanding of the biology of cya-nobacteria as of appellants’ filing date, as well as the limited disclosure by appellants of particular cyanobacterial genera operative in the claimed invention, we are not persuaded that the PTO erred in rejecting claims 1-46 and 50-51 under § 112, first paragraph. There is no reasonable correlation between the narrow disclosure in appellants’ specification and the broad scope of protection sought in the claims encompassing gene expression in any and all cya-nobacteria. See In re Fisher, 427 F.2d 833, 839, 166 U.S.P.Q. 18, 24 (CCPA 1970) (the first paragraph of § 112 requires that the scope of the claims must bear a reasonable correlation to the scope of enablement provided by the specification).
In so doing we do not imply that patent applicants in art areas currently denominated as “unpredictable” must never be allowed generic claims encompassing more than the particular species disclosed in their specification. It is well settled that patent applicants are not required to disclose every species encompassed by their claims, even in an unpredictable art. In re Angstadt, 537 F.2d 498, 502-03, 190 U.S.P.Q. 214, 218 (CCPA 1976). However, there must be sufficient disclosure, either through illustrative examples or terminology,
Remaining dependent claim 47 recites a cyanobacterium which expresses the chimeric gene of claim 1, wherein the cyanobac-terium is selected from among the genera Anacystis and Synechocystis. Claim 48, which depends from claim 47, is limited to the cyanobacterium Synechocystis 6803. The PTO did not separately address these claims, nor indicate why they should be treated in the same manner as the claims encompassing all types of cyanobacteria. Although these claims are not limited to expression of genes encoding particular Bacillus proteins, we note what appears to be an extensive understanding in the prior art of the numerous Bacillus proteins having toxicity to various insects. The rejection of claims 47-48 under § 112 will not be sustained.
CONCLUSION
The rejection of claims 1-48 and 50-52 under 35 U.S.C. § 103 is reversed. The rejection of claims 1-46 and 50-51 under 35 U.S.C. § 112, first paragraph, is affirmed and the rejection of claims 47 and 48 thereunder is reversed.
AFFIRMED-IN-PART, REVERSED-IN-PART.
. Basic vocabulary and techniques for gene cloning and expression have been described in In re O'Farrell, 853 F.2d 894, 895-99, 7 U.S.P.Q.2d 1673, 1674-77 (Fed.Cir.1988), and are not repeated here.
. All living cells can be classified into one of two broad groups, procaryotes and eucaryotes. The procaryotes comprise organisms formed of cells that do not have a distinct nucleus; their DNA floats throughout the cellular cytoplasm. In contrast, the cells of eucaryotic organisms such as man, other animals, plants, protozoa, algae and yeast have a distinct nucleus wherein their DNA resides.
. "Transformed” cyanobacteria are those that have successfully taken up the foreign Bacillus DNA such that the DNA information has become a permanent part of the host cyanobacte-ria, to be replicated as new cyanobacteria are generated.
. "Expression" of a gene refers to the production of the protein which the gene encodes; more specifically, it is the process of transferring information from a gene (which consists of DNA) via messenger RNA to ribosomes where a specific protein is made.
. In the context of the claimed invention, “selectable markers” or "marker genes” refer to antibiotic-resistance conferring DNA fragments, attached to the gene being expressed, which facilitate the selection of successfully transformed cyanobacteria.
. 12 Nucleic Acids Res. 8917 (1984).
. Chloramphenicol is an antibiotic; CAT is an enzyme which destroys chloramphenicol and thus imparts resistance thereto.
. 137 Biochem. and Biophys. Res. Comm. 748 (1986).
. 33 Gene 151 (1985).
. 189 Mol. Gen. Genet. 181 (1983).
. 203 Mol. Gen. Genet. 505 (1986).
. 140 J. Bacteriology 246 (1979).
. RNA polymerase, the enzyme responsible for making RNA from DNA, binds at specific nucleotide sequences (promoters) in front of genes in DNA, and then moves through the gene making an RNA molecule that includes the information contained in the gene. Initiation specificity is the ability of the RNA polymerase to initiate this process specifically at a site(s) on the DNA template.
. 81 Proc. Natl. Acad. Sci. USA 5961 (1984).
. 204 Mol. Gen. Genet. 185 (1986).
. 30 Gene 211 (1984).
. 27 Gene 289 (1984).
. Denotes different species or organism.
. MPEP 706.03(n), "Correspondence of Claim and Disclosure," provides in part:
In chemical cases, a claim may be so broad as to not be supported by [the] disclosure, in which case it is rejected as unwarranted by the disclosure....
. MPEP 706.03(z), “Undue Breadth,” provides in part:
[I]n applications directed to inventions in arts where the results are unpredictable, the disclosure of a single species usually does not provide an adequate basis to support generic claims. In re Sol, 1938 C.D. 723; 497 O.G. 546. This is because in arts such as chemistry it is not obvious from the disclosure of one species, what other species will work. In re Dreshfield, 1940 C.D. 351; 518 O.G. 255 gives this general rule: "It is well settled that in cases involving chemicals and chemical compounds, which differ radically in their properties it must appear in an applicant’s specification either by the enumeration of a sufficient number of the members of a group or by other appropriate language, that the chemicals or chemical combinations included in the claims are capable of accomplishing the desired result.” ...
. Stedman's Medical Dictionary 1139 (24th ed. 1982) (definition of "Procaryotae"). Procaryotic organisms are commonly classified according to the following taxonomic hierarchy: Kingdom; Division; Class; Order; Family; Genus; Species. 3 Bergey’s Manual of Systematic Bacteriology 1601 (1989).
. The enablement rejection in this case was not based upon a post-filing date state of the art, as in In re Hogan, 559 F.2d 595, 605-07, 194 U.S.P.Q. 527, 536-38 (CCPA 1977). See also United States Steel Corp. v. Phillips Petroleum Co., 865 F.2d 1247, 1251, 9 U.S.P.Q.2d 1461, 1464 (Fed.Cir.1989) (citing Hogan); Hormone Research Found., Inc. v. Genentech, Inc., 904 F.2d 1558, 1568-69, 15 U.S.P.Q.2d 1039, 1047-48 (Fed.Cir.1990) (directing district court, on remand, to consider effect of Hogan and United States Steel on the enablement analysis of Fisher), cert. dismissed, — U.S. —, 111 S.Ct. 1434, 113 L.Ed.2d 485 (1991). We therefore do not
. The first paragraph of § 112 requires nothing more than objective enablement. In re Marzocchi, 439 F.2d 220, 223, 169 U.S.P.Q. 367, 369 (CCPA 1971). How such a teaching is set forth, either by the use of illustrative examples or by broad terminology, is irrelevant. Id.
Dissenting Opinion
dissenting.
An appeal is not a second opportunity to try a case or prosecute a patent application, and we should not allow parties to “undertake to retry the entire case on appeal.” Perini America, Inc. v. Paper Converting Machine Co., 832 F.2d 581, 584, 4 U.S.P.Q.2d 1621, 1624 (Fed.Cir.1987); Eaton Corp. v. Appliance Valves Corp., 790 F.2d 874, 877, 229 U.S.P.Q. 668, 671 (Fed. Cir.1986). But that is precisely what the court has permitted here. The PTO conducted a thorough examination of the prior art surrounding this patent application and concluded the claims would have been obvious. The board’s decision based on the examiner’s answer which comprehensively explains the rejection is persuasive and shows how the evidence supports the legal conclusion that the claims would have been obvious. Yet, the court ignores all this and conducts its own examination, if you will, as though the examiner and board did not exist. Even if I thought this opinion were more persuasive than the board's, I could
The scope and content of the prior art, the similarity between the prior art and the claims, the level of ordinary skill in the art, and what the prior art teaches are all questions of fact. Graham v. John Deere Co., 383 U.S. 1, 17, 86 S.Ct. 684, 693-94, 15 L.Ed.2d 545, 148 U.S.P.Q. 459, 467 (1966); Jurgens v. McKasy, 927 F.2d 1552, 1560, 18 U.S.P.Q.2d 1031, 1037 (Fed.Cir.1991). And “[wjhere there are two permissible views of the evidence, the factfinder’s choice between them cannot be clearly erroneous.” Anderson v. City of Bessemer City, 470 U.S. 564, 574, 105 S.Ct. 1504, 1511-12, 84 L.Ed.2d 518 (1985). The mere denomination of obviousness as a question of law does not give the court license to decide the factual matters afresh and ignore the requirement that they be respected unless clearly erroneous. In re Woodruff, 919 F.2d 1575, 1577, 16 U.S.P.Q.2d 1934, 1935 (Fed.Cir.1990); In re Kulling, 897 F.2d 1147, 1149, 14 U.S.P.Q.2d 1056, 1057 (Fed. Cir.1990). There may be more than one way to look at the prior art, but on this record we are bound by the PTO’s interpretation of the evidence because it is not clearly erroneous and its conclusion is unassailable. I would affirm on that basis.
