261 F.3d 1345 (Fed. Cir. 2001)
MYCOGEN PLANT SCIENCE, INC. and Agrigenetics, inc.,  Plaintiffs-Appellants,v.MONSANTO COMPANY,  Defendant- Appellees.
00-1127
United States Court of Appeals for the Federal Circuit
DECIDED: August 14, 2001

Appealed from: United States District Court for the Southern District of California  Judge Napoleon A. Jones, Jr.
Daniel J. Thomasch, Orrick, Herrington & Sutcliffe LLP, of New York, New  York, for plaintiffs-appellants. With him on the brief were Richard W.  Mark, Robert M. Isackson, and Geoffrey W. Millsom, of New York, New York;  and Craig R. Kaufman, of Menlo Park, California. Of counsel was Marc P.  Berger, of New York, New York.
John F. Lynch, Howrey Simon Arnold & White, LLP, of Houston, Texas, for  defendant-appellee. With him on the brief were Richard L. Stanley, Susan K.  Knoll, Melinda L. Patterson, Michael E. Lee, and Steven G. Spears.
ON PETITION FOR REHEARING
Before CLEVENGER, BRYSON, and LINN, Circuit Judges.
BRYSON, Circuit Judge.


1
Based on the prosecution history of Mycogen's U.S. Patent No. 5,380,831  (the '831 patent), we held in our initial opinion in this case that Mycogen  is not entitled to invoke the doctrine of equivalents with respect to  claims 13 and 14 of the patent. 252 F.3d 1306, 1319-20, 58 USPQ2d 1891,  1901-02. In its petition for rehearing, Mycogen contends that we  misunderstood the prosecution history of the '831 patent and, as a result,  mistakenly held the doctrine of equivalents inapplicable to claims 13 and  14.


2
The prosecution history leading to the issuance of claims 13 and 14 of the  '831 patent is complex. We did not describe it in detail in our initial  opinion, but have done so here. Although Mycogen contends that the details  of the prosecution history require a different analysis of the doctrine of  equivalents issue, we are not persuaded that anything in the prosecution  history to which Mycogen has called our attention justifies a different  result from the one reached in our original opinion.


3
In brief summary, the prosecution history of claims 13 and 14 reveals that  Mycogen first applied for claims providing broad coverage, and then  subsequently engaged in a long prosecution negotiation with the Patent and  Trademark Office ("PTO"). During the course of the prosecution, Mycogen  narrowed the scope of its application through a series of increasingly  narrow claims. The PTO, however, rejected all of those claims and  ultimately proposed language that limited what became claims 13 and 14 to  segments of a specific DNA sequence disclosed in the application. Mycogen  agreed to the proposed language and agreed to cancel its broader related  claims. It is that series of events, described in more detail below, that  provides the factual background for Mycogen's doctrine of equivalents  argument.


4
Mycogen's application No. 07/242,482 (the '482 application), filed on  September 9, 1988, included application claims 1, 3, and 4:


5
1.   A synthetic  gene  designed  to  be highly expressed in plants comprising a DNA sequence encoding an insecticidal protein which is functionally equivalent to a native insecticidal protein of Bt.


6
3. A synthetic gene of claim 1 wherein said DNA sequence is that presented  in Figure 1, spanning nucleotides 1 through 1793.


7
4. A synthetic gene of claim 1 wherein said DNA sequence is that presented  in Figure 1 spanning nucleotides 1 through 1833.


8
Those claims were rejected on a number of grounds. Claim 1 was rejected  under the second paragraph of 35 U.S.C. § 112 as being indefinite, and all  claims were rejected under the first paragraph of section 112 because the  specification was enabling only for claims limited to dicot plant cells.  The examiner observed that the disclosure was enabling only for the  specific sequence shown in Figure 1, and that in view of the  unpredictability of foreign gene expression, it did not appear that any  functionally equivalent synthetic gene would be effective in any plant  cell. Finally, the claims were rejected as obvious.


9
In response to arguments made by Mycogen, the examiner again concluded that  the disclosure was enabling only for the specific sequence shown in Figure  1. The examiner further remarked that Mycogen had not provided evidence  that the sequence of Figure 1 or any other sequence is highly expressed in  plants and reiterated that, in light of the unpredictability of expression,  even very similar genes might not express a protein that would be an  effective toxin.


10
Following final rejection of the '482 application, Mycogen filed a  continuation that became application No. 07/827,844 (the '844 application).  In that application, claims 3 and 4 from the '482 application were amended  to depend from new application claim 31, which was significantly narrower  than '482 application claim 1. The change in dependency had the effect of  narrowing the scope of claims 3 and 4. Claim 31 provided as follows:


11
31. A synthetic gene designed to be highly expressed in plants comprising a


12
DNA sequence encoding a Bt insect toxic polypeptide which is functionally  equivalent to a native insecticidal protein of Bt, having toxicity to a  specific insect, and wherein said synthetic gene is designed by modifying a  native Bt gene by at least one of a plurality of factors affecting Bt mRNA  synthesis or degradation in plants selected from the group of factors  consisting of (a) preferred codon usage, (b) A+T base content, (c) CG and  TA doublet avoidance indices, (d) RNA destabilizing sequence, (e)  translation initiation sequence, (f) plant polyadenylation signal, (g) RNA  degradation signal, (h) polymerase II termination sequence, (i) CUUCGG  hairpin and (j) plant consensus split site.


13
The claims of the '844 application were rejected under the second paragraph  of 35 U.S.C. § 112 for indefiniteness. In addition, claim 31 was rejected  under the first paragraph of 35 U.S.C. § 112 on written description and  enablement grounds. The examiner again noted that the disclosure was  enabling only for the specific sequence shown in Figure 1 of the  specification. Although the application recited a synthetic gene encoding a  functional equivalent of any native Bt protein, the examiner pointed out  that the applicants had shown only one Bt-derived synthetic gene, the  sequence of which was shown in Figure 1. The examiner concluded that the  applicants "have provided insufficient guidance to justify the breadth of  the claims." The examiner reiterated that there must be a reasonable  predictability that following the teaching of the disclosure will result in  the claimed invention, and found no assurance that any of the claims  recited any operable species. Although Mycogen had submitted declarations  attempting to provide such assurance, the examiner found the declarations  insufficient. In particular, the examiner found that the testing supporting  the declarations did not support the broad claims because only one  construct was tested, and the testing did not support claims 3 and 4  because the declaration did not refer to the construct of Figure 1. In  addition, the examiner rejected claim 31 for obviousness.


14
In response to that office action, Mycogen amended the '844 application.  It canceled claim 31, substituted new claim 35 in its place, and added  claim 36. Claims 35 and 36, from which claims 3 and 4 were made to depend,  were narrower than claim 31. Once again, then, the amendment had the effect  of narrowing the scope of claims 3 and 4. Also, independent claim 51 and  dependent claim 52, which contained the Figure 1 limitations, were added.  The new and modified claims provided as follows:


15
36. A synthetic gene designed to be highly expressed in plants comprising a DNA sequence encoding a Bt insecticidal protein, said synthetic gene having  modified codons in a Bt coding region.


16
35. A synthetic gene of claim 36 wherein said DNA sequence is characterized  by at least one of a plurality of factors selected from the group of  factors consisting of: (a) utilization of plant preferred codon usage to  within about 75% of the frequency of codon usage preferred by plants as in  Table 1, (b) utilization of an A+T base content substantially equal to the  A+T base content found in plant structural genes as in Table 1, (c)  utilization of CG and TA doublet avoidance indices substantially equal to  those of selected a host plant, (d) utilization of a plant translation  initiation sequence, (e) elimination of plant polyadenylation signals  comprising those having AATAAA, AATGAA, AATAAT, AATATT, GATAAA and AATAAG  motifs, (f) elimination of polymerase II termination sequences, CAN7-  9AGTNNAA, (g) elimination of CUUCGG hairpins and (h) elimination of plant  consensus splice sites, including 5'=AAG:GTAAGT and  3'=TTTT(Pu)TTT(Pu)T(Pu)T(Pu)T(Pu)TGCAG:C.


17
3. A synthetic gene of claim 35 wherein said DNA sequence is that presented  in Figure 1, spanning nucleotides 1 through 1793.


18
4. A synthetic gene of claim 35 wherein said DNA sequence is that presented  in Figure 1, spanning nucleotides 1 through 1833.


19
51. A synthetic gene designed to be highly expressed in plants comprising a  DNA sequence encoding a Bt insecticidal protein, said DNA sequence being  that presented in Figure 1, spanning nucleotides 1 through 1793.


20
52. A synthetic gene of claim 51 wherein said DNA sequence spans  nucleotides 1 through 1833.


21
All of those claims were rejected under the first paragraph of 35 U.S.C. §  112 on written description and enablement grounds. Claims 3, 4, and 35 were  also rejected under the second paragraph of 35 U.S.C. § 112 for  indefiniteness. In addition, the examiner rejected claims 3, 4, 51, and 52  under the fourth paragraph of 35 U.S.C. § 112 for being in improper  dependent form or failing to further limit the subject matter of a previous  claim. The examiner again found that the disclosure enabled only the Figure  1 sequence and found, in light of the unpredictable effect of changes in  gene sequences, that even if the declarations offered by Mycogen clarified  that the Figure 1 construct was tested and operable, that evidence would be  helpful only if the claims were limited to the sequence set forth in Figure  1.


22
Following an interview, new claim 53 was added, and claims 3 and 4 were  again amended, this time to make them depend from claim 53. The other  pending claims were cancelled. The new claims provided as follows:


23
53. A synthetic Bt gene derived from a native Bt gene and expressible in  plants at a level higher than the corresponding native Bt gene, wherein the  DNA sequence of the native Bt gene has been modified in the synthetic gene  to contain a frequency of codon usage that more closely resembles the  frequency of codon usage of the plant in which it is to be expressed, and  wherein the modified DNA sequence encodes substantially the same amino acid  sequence as did the native Bt DNA sequence from which it was derived.


24
3. A synthetic gene of claim 53 wherein said DNA sequence is that presented  in Figure 1, spanning nucleotides 1 through 1793.


25
4. A synthetic gene of claim 53 wherein said DNA sequence is that presented  in Figure 1, spanning nucleotides 1 through 1833.


26
Claim 53 was then rejected under the second paragraph of section 112 as  indefinite. Again, the examiner stated that there must be reasonable  predictability that following the teaching of the disclosure will result in  the claimed invention, and found that there was no assurance that the  claimed invention was enabled for the scope recited. The examiner withdrew  the prior rejection of claims 3 and 4 under the first paragraph of section  112 in view of the amendments and arguments made, specifically the  clarification that the construct tested as described in the submitted  declarations was that of Figure 1. Finding the declarations persuasive with  regard to claims 3 and 4 only, the examiner stated that it was "impossible  to determine how much experimentation was required to obtain the one  success exemplified." Accordingly, the examiner concluded that "the claims  should be limited to the sequence shown in Figure 1 as disclosed in the  Examples of the instant application." The examiner stated that claims 3 and  4 would be allowable if rewritten in independent form. Following another  interview, Mycogen agreed to cancel the non-allowed claims and agreed to  the examiner's proposed language amending claims 3 and 4 as follows:


27
3. A synthetic gene comprising the DNA sequence presented in Fig. 1,  spanning nucleotides 1 through 1793.


28
4. A synthetic gene comprising the DNA sequence presented in Fig. 1,  spanning nucleotides 1 through 1833.


29
Those claims issued as claims 13 and 14 in that form.


30
As we explained in our initial opinion in this case, the court in Festo  Corp. v. Shoketsu Kinzoku Kogyo Kabushiki Co., 234 F.3d 558, 588, 56 USPQ2d  1865, 1887 (Fed. Cir. 2000) (en banc), cert. granted, 121 S. Ct. 2519  (2001), held that cancellation of a claim and replacement with another  claim having an added limitation had the effect of narrowing the scope of  the original claim and therefore should be treated as a claim amendment  that created a total bar to the doctrine or equivalents with respect to the  limitation that was in effect added to the original claim. In Festo, as  here, the court had under consideration a claim limitation that was not  present in the original independent claim but was present in an original  dependent claim and was imported from the dependent claim into the  independent claim that ultimately issued.


31
In Festo, one of the issued claims of the Stoll patent recited "a sleeve  made of magnetizable material." Id. at 580, 56 USPQ2d at 1881. The  independent claim of the application, claim 1, did not include that  limitation, although a dependent claim, claim 8, did include it. Id. at  582-83, 56 USPQ2d at 1883. Following rejection of the original claims, the  applicant submitted new claims, including an independent claim that  contained the "magnetizable sleeve" element. That claim was subsequently  allowed and issued.


32
In analyzing that sequence of events, we concluded that prosecution history  estoppel applied because the amendment narrowed the literal scope of the  original independent claim, even though the narrowing was effected through  the addition of a new claim rather than through an amendment to the  original claim. We explained:


33
To determine whether a claim amendment gives rise to prosecution history  estoppel, we first must determine whether the amendment narrowed the literal scope of the claim. Here we are presented with the situation where  the added claim element was introduced through a new claim, instead of  through an amendment to an original claim. Nevertheless, the addition of  the magnetizable sleeve claim element can be said to have narrowed the  scope of the original claim because the new claim replaced the original  claim. Specifically, the only original independent claim, which did not  recite a magnetizable sleeve, was replaced with an independent claim which  does recite a magnetizable sleeve. Because the amendment narrowed the  literal scope of the claim, we must determine whether Festo has established  that it was made for a reason unrelated to patentability.


34
Festo, 234 F.3d at 587-88, 56 USPQ2d at 1887. Because Festo had not shown  that the scope of the independent claim was changed for a purpose unrelated  to patentability, we held that application of the doctrine of equivalents  was barred as to that claim element. Id. at 588, 56 USPQ2d at 1888.


35
That analysis is equally applicable to the claims at issue in this case.  As in Festo, the limitations at issue in this case were included in  dependent application claims and were later incorporated into the  independent claims that were allowed and issued. As in Festo, the scope of  the independent claim was clearly limited when it was replaced by a claim  the language of which was drawn from a prior dependent claim.


36
As described above, the examiner in this case made clear that in light of  the unpredictability of expression of synthetic genes, demonstration of  enablement was required for allowance. The examiner also was clear that  when only one synthetic gene was shown to be enabled, no broader claim  scope was allowable. Faced with these rejections, Mycogen acquiesced in the  examiner's proposal to cancel all claims except those specifically reciting  the Figure 1 sequence. Thus, the prosecution history reveals that what the  examiner ultimately proposed, and Mycogen accepted, was claim language  limited to sequences taken from the preferred embodiment set forth in  Figure 1. Under these circumstances, it is appropriate to limit Mycogen to  the literal scope of the claims to which it agreed. We therefore conclude,  as we did in our original opinion, that prosecution history estoppel  applies to the Figure 1 limitations that were imported into independent  claims 13 and 14 from the original dependent claims, and that Mycogen is  barred from asserting the doctrine of equivalents with regard to those  claim limitations.


37
The petition for rehearing is denied.

