Citations
- 445 F. Supp. 2d 531
Full opinion text
MEMORANDUM OPINION
TILLEY, Chief Judge.
This Memorandum Opinion states the findings of fact and conclusions of law in connection with the trial held in this matter from August 22 to September 1, 2000. For the reasons outlined below, the Court finds that for patent 6,040,497 Rick De-Rose, Georges Freyssinet, Michel Lebrun, Bernard Leroux, and Alain Sailland are entitled to be named as joint inventors; but for patent 5,554,798 it is determined that conception had occurred prior to any of the applicants making a significant inventive contribution and that their application should be denied. The Director of the Patent and Trademark Office will be directed to add those individuals as joint inventors on the 497 patent.
I. PROCEDURAL HISTORY
Litigation between these parties has been extensive and complex. It has been ongoing for several years and prior proceedings include a lengthy trial on bifurcated issues. The Court’s 136-page Memorandum Opinion, filed February 8, 2000 [Doc. #538], outlines the history of the case and the rulings made in connection with the previous trial.
As will be developed in this opinion, Rhone-Poulenc S.A. (now known as “Aven-tis CropScience S.A.” but hereinafter referred to as “RPA”) and DeKalb Genetics Corporation (“DeKalb”) entered into a collaboration, informally in 1990 and formally in 1991, to develop glyphosate resistant corn. RPA’s scientists were to find or develop genetic material which could add the trait of glyphosate resistance and De-Kalb scientists were to use the material to “transform” corn by implanting it within cells which could be regenerated into fertile plants that would pass the trait to succeeding generations. During the collaboration, RPA’s scientists constructed genetic material which was used by De-Kalb in the transforming of corn and the regeneration and hybridizing of plants that were resistant to large, commercial applications of glyphosate.
DeKalb contends that those glyphosate resistant plants, including that commercialized as “Roundup Ready®” Corn, are covered by the ’497 and ’798 patents. The issue currently before the Court is whether one or more of the RPA scientists— Drs. Rick DeRose, Georges Freyssinet, Michel Lebrun, Bernard Leroux, and/or Alain Sailland — should be listed as co-inventors on either or both of those patents. Title 35 of the United States Code § 256 authorizes a United States District Court to correct the inventors listed on U.S. patents.
The Court held a trial from August 22 to September 1, 2000 before an advisory jury. The jury found that for both of the patents at issue, RPA had proven the following by clear and convincing evidence: 1) that all five individuals contributed to the conception of the claims at issue; 2) that the claims were the product of either a collaboration between RPA and DeKalb scientists or work under a common direction; 3) that the contributions of the five scientists were not insignificant in quality when measured against the dimension of the full inventions; 4) that the five individuals did more than contribute well known principles or explain concepts that are well known or the current state of the art [Doc. # 661]. More specifically, the jury found that the five individuals contributed to the ’497 patent by providing De-Kalb with significant DNA constructs that were successful at imparting glyphosate resistance in corn and which were included in the claimed transformation events GG25, GA21, GJ11, and FI117. In regard to the ’798 patent, the jury found that the five individuals contributed to the conception of fertile transgenic corn containing DNA constructs encoding EPSP synthase that provide glyphosate resistance to corn.
The parties have submitted lengthy post-trial briefs suggesting findings of fact and conclusions of law. After reviewing the parties’ filings and reviewing the evidence presented at trial, the Court now enters this Memorandum Opinion which will constitute its findings of fact, made by a clear and convincing standard, and its conclusions of law.
II. FINDINGS OF FACT
The findings relating to joint inventor-ship issues such as conception and inventive contributions are dependent upon an understanding of the scientific problem or problems the parties were trying to resolve. Parts A and B of this section will address the object of the parties’ undertaking and the pertinent science involved.
A.
Glyphosate, manufactured and marketed by Monsanto Company as “Roundup®”, is an effective and environmentally safe herbicide. Since its toxic action derives from the interruption of a plant’s own food production occurring in the ehloroplasts, it has no injurious effect on humans or other animals, and it biodegrades quickly in the soil. When applied in an appropriate amount, it is effective to kill all plants with green foliage. “Roundup Ready®” corn contains genetically engineered DNA making it resistant to glyphosate and enabling farmers to spray an entire field of corn, killing the weeds without adversely affecting the corn. Finding a way to impart glyphosate resistance to corn — the world’s largest cash crop — was a long-term, worldwide effort of a number of researchers.
B.
Acting at the cellular level, the chemical structure of glyphosate allows it to bond in the chloroplast with EPSPS enzymes and, thereby, block the enzymes’ necessary catalytic function in the plant’s production of its own food. When a plant is subjected to glyphosate in amounts sufficient to prevent it from sustaining itself, it dies.
Specifically, the “string” of amino acids comprising a naturally occurring EPSPS enzyme (also referred to as an EPSPS “protein”) forms a three dimensional, coil-like shape. Within the structure of the coil there is a “hole” or “cave” where, in the absence of glyphosate, a shikimate molecule and a PEP molecule fit and become bonded to form EPSP. When glypho-sate is present, a molecule of glyphosate slips into the cave and bonds with the EPSPS enzyme in such a way as to block the PEP from entering. (DeRose, Trial Tr. vol. 1,113-16,133.)
Once it was determined that glypho-sate’s toxicity related to bonding with EPSPS enzymes, the research objective was to find a shape for the enzyme that would allow PEP into the cave but block glyphosate. (Padgette, Trial Tr. vol IV, 579.) Modifications in the amino acid sequence of EPSPS enzymes in one type of plant would not necessarily be effective in others. (Padgette, Trial Tr. vol IV, 584.) For example, modifications which had imparted glyphosate resistance in soybeans or in tobacco had not successfully imparted it to corn, a monocot.
Modifications of an enzyme are not made at the enzyme level but to the gene which is ultimately responsible for the creation of the enzyme. (Freyssinet, Trial Tr. vol. IV, 626-27, 687.) Genes are DNA, located within the chromosomes in the nucleus of a cell. Each functioning gene controls a specific process going on somewhere within the cell. An excellent description of the fundamental biochemistry involved in this process — also supported by the testimony in this case — is found in Mycogen Plant Science, Inc. v. Monsanto Co., 61 F.Supp.2d 199 (D.Del.1999), adopted by, Mycogen Plant Science, Inc. v. Monsanto Co., 243 F.3d 1316, 1323-24 (Fed.Cir.2001):
Organisms, like plants and animals, are made up of cells. Genes are comprised of DNA (deoxyribonucleic acid), which encodes the necessary information for cells to reproduce and to produce specific proteins.
DNA consists of two long chains or strands that wrap around each other in a shape known as a double-stranded spiral helix. Visually, a molecule of DNA resembles a twisted ladder. The sides of the ladder are connected by rungs made up of pairs of molecules called nucleotides. Four different nucleotides, each containing one of the bases adenine (“A”), guanine (“G”), cytosine (“C”) and thymine (“T”), form the particular DNA make-up of genes. A particular DNA molecule can be graphically represented by listing the nucleotide sequences making up that DNA molecule.
Because of the nucleotides’ chemical make-up, A will only pair with T, and C will only pair with G. This strict complementary pairing means that the order of the nucleotides on one side of a DNA rung determines the order on the other side of the rung. Therefore, each rang of the ladder is composed of one pair consisting of A and T, or C and G. Each rung is called a nucleotide pair, and the order in which these nucleotide pairs appear on the DNA ladder constitutes the genetic code for the cell.
DNA directs cells to make proteins through a two-step process of transcription and translation. In the first step, transcription, information is transferred from DNA to an RNA, or ribonucleic acid, molecule. RNA that codes for a protein is called messenger RNA (“mRNA”).
RNA is a long single strand of linked nucleotides similar to DNA. However, one of the differences between DNA and RNA is that RNA contains the base uracil (“U”) in place of thymine. In transcription, specific nucleotide sequences on the DNA determine where the RNA copy begins and ends.
In the second step, translation, the nucleotide sequence of the mRNA is translated into the amino acid sequence of the corresponding protein. For this translation work, a complex structure known as a ribosome reads the mRNA nucleotide sequence and generates amino acids. These amino acids are then assembled into proteins. In this way, ribosomes carry out protein synthesis.
Ribosomes read a nucleotide sequence in sets of three nucleotides, known as codons. Each codon directs the ribo-some to select a certain amino acid. For example, GCT is a codon directing the ribosome to select the amino acid alanine. Just as nucleotides are the basic units of DNA, amino acids are the basic units of proteins. Thus, a given series of codons specifies a sequence of amino acids comprising a particular protein. A protein can contain few or many amino acids. For example, some Bt pesticidal proteins contain more than 600 amino acids.
While there are 61 possible codons, there are only 20 amino acids. Some amino acids can be specified by more than one codon. In other words, one codon can be substituted for another in the gene without changing the amino acid and resulting protein. For instance, the amino acid alanine is specified by four different codons: GCT, GCG, GCC and GCA. Two very different series of codons could produce the exact same series of amino acids. In fact, most amino acids are specified or coded by more than one codon.2
1. There are 61 codons because a co-don is a sequence of three nucleotides. For mRNA, there are four nucleotide possibilities, A, G, C and U. Thus, three nucleotides, each consisting of four possibilities, A, G, C or U, are represented mathematically as 43 (4 x 4 x 4), which equals 64 possible codons. Of the 64 possible codons, however, three codons, UAA, UAG and UGA, do not correspond to amino acids. Thus, there are 61 co-dons. See, e.g., McGraw-Hill Encyclopedia of Science & Technology, “Gene” at Vol. 7, page 740 (1997). For general information on genetics, see In re O’Farrell, 853 F.2d 894, 895-99, 7 USPQ2d 1673, 1674-77 (Fed.Cir.1988). 2. Scientists variously refer to this as “redundancy” or “degeneracy” in the genetic code. The term “unique” refers to an amino acid coded by only a single codon. See, e.g., Amgen, Inc. v. Chugai Pharm. Co., 927 F.2d 1200, 1207-08 n. 4, 18 USPQ2d 1016, 1022 n. 4 (Fed.Cir.1991).
Mycogen Plant Science, 61 F.Supp.2d at 207-08.
A gene “encoding an EPSPS enzyme” is a gene whose nucleotide sequence, following transcription in the nucleus and translation in the cytoplasm, results in the specific amino acid sequence of a protein or enzyme known, immediately after translation, as an “EPSPS precursor enzyme.” As the ribosome is reading the codons and adding the amino acids specified, the precursor enzyme is folding, assuming the three dimensional, coil-like shape characteristic of that species’ EPSPS enzyme.
A gene coding for an EPSPS protein in a plant (as opposed to a bacterium) also codes for an amino acid sequence known as a transit peptide. The transit peptide is attached to the amino acids of the EPSPS and has the function of targeting the protein to a chloroplast and accomplishing passage through the chloroplast wall. Upon entry into the chloroplast, the transit peptide portion is cleaved, leaving the “mature” EPSPS protein. (DeRose, Trial Tr. vol 1,123-31.)
One of the important regions of a gene’s nucleotide sequence is the promoter. The promoter is the first part of a gene and acts as the “off/on switch,” attracting the RNA polymerase structure in the nucleus to approach and begin the transcription phase, copying from the DNA into mRNA. The frequency with which the promoter attracts the RNA polymerase affects the number of proteins ultimately being translated. It also determines in what plant part the production of that protein will be more active. For example, in humans, promoters “tell[ ] the genes which make the hair and the fingernails to only make hair and fingernails where fingernails and hair are supposed to be made.” (DeRose, Trial Tr. vol 1,122-24.)
These processes within a plant cell are central to the research and development of glyphosate resistance in corn.
C.
RPA is a worldwide manufacturer and vendor of diversified agricultural products, and is engaged in chemical and biotechnological research and development with particular interests in the area of weed control and crops. Monsanto manufactures and sells a diversified line of agricultural products as well, including herbicides, and is engaged in biotechnological research and development. DeKalb, which became a fully-owned subsidiary of Monsanto in December 1998, is involved in agricultural genetics and biotechnology for corn seed, and is one of the largest corn seed suppliers in the United States.
From the mid-1980s, researchers, including those from RPA, DeKalb, Cal-gene, and Monsanto had worked to identify a means to impart glyphosate resistance to commercial crops so that farmers could spray an entire field with glyphosate, kill unwanted vegetation, and leave their crop unaffected. In that time frame, both RPA and DeKalb were collaborating with Cal-gene. Calgene’s role was significant at the time because Dr. Luca Comai, a Calgene scientist, had identified CT7 (also referred to as the “aroA”), a mutagenized EPSPS gene in the bacteria Salmonella typhymu-rium which showed some resistance to glyphosate. Dr. Comai had published his work with CT7 in 1985 and hope existed that his success in finding the gene would lead to further success in imparting gly-phosate resistance to crops. (DeRose, Trial Tr. vol. II, 308-10.)
Dr. Comai had isolated CT7 by treating the bacteria with ethyl methane sulfonate (EMS), a compound capable of causing random changes in the DNA of the bacteria. (Freyssinet, Trial Tr. vol. IV, 594.) He identified CT7 as a gene with a mutation in which the amino acid Serine had been substituted for the amino acid Proline at the “101” position (noted as “Pro Ser, 101”). (DeRose, Trial Tr. vol. II, 327 & vol. I, 138-39; Lebrun, Trial Tr. vol. III, 542; Freyssinet, Trial Tr. vol. IV, 666-68; Comai, Trial Tr. vol. V, 854-57.)
In the collaboration between RPA and Calgene, Calgene provided the CT7 and did most of the research to find new, more resistant genes. RPA did much of the research to develop more effective transit peptides and promoters that would enhance the resistance of the genes. In addition, RPA provided most of the funding. A Scientific Committee comprised of two members each from Calgene and RPA oversaw the scientific work of the collaboration.
When experiments with CT7 were proving unsuccessful, the Scientific Committee directed further experiments that led to the development of B808, another randomly mutagenized aroA bacterial gene. B808 encoded an EPSPS enzyme with three mutations, one of which was a Threonine to Isoleucine mutation at the “97” position (Threo Iso, 97). (Freyssinet, Trial Tr. vol. IV, 596, 597-98, 609; Comai, Trial Tr. vol. V, 859.) The B808 gene was more successful in vitro than CT7 at imparting glyphosate resistance. More experimentation began in 1989 at both Calgene and RPA to learn whether the Threo Iso, 97, was the substitution conferring resistance.
The use of plant EPSPS genes — in addition to bacterial EPSPS genes — for muta-genesis had been discussed from time to time both within Calgene and within RPA. (Lebrun, Trial Tr. vol. Ill, 521-24.) Additionally, the idea had been debated during meetings between RPA and Calgene, but Dr. Comai had never made a concrete proposal to pursue the idea. (Comai, Trial Tr. vol. V, 876-77, 886). Instead, he had elected to continue research with the Salmonella gene. (Comai, Trial Tr. vol. V, 877, 879-81, 888-89.)
At a committee meeting between Cal-gene and RPA, Dr. Comai suggested site mutagenesis of a wild type bacterial EPSPS gene by combining the Pro Ser, 101 mutation from the CT7 AroA gene with the Threo Iso, 97 mutation from the B808 randomly mutated bacterial gene. (Comai, Trial Tr. vol. V, 863-67; DTX 1477 at RPA 031676 & 031685.) At the meeting, Dr. Freyssinet proposed that RPA would mutate a maize gene. (Comai, Trial Tr. vol. V, 893; DTX 1477 at RPA 031676.)
As Calgene was beginning the process of combining the “97” and “101” mutations, it was discovered that B808 was toxic to the E. coli bacteria in which it was being cloned. (Freyssinet, Trial Tr. vol. IV, 616-17.) The minutes of the October 1989 RPA-Calgene Scientific Committee stated that B808 was “clearly the worst” in terms of toxicity and that “Toxicity to E. Coli is triggered by 97 thr isoleu mutation.” (PTX 1431 at CAL 004229.) By the end of 1989, Calgene and RPA had determined that no progress had been made with the bacterial aroA genes. (PTX 1431 at CAL 004229.) Dr. Comai left Calgene, and technical collaboration between RPA and Calgene on glyphosate resistance ended in 1989.
DeKalb also had an ongoing collaboration agreement with Calgene around the same time. In 1990, RPA and DeKalb began an informal collaboration with the ultimate goal of genetically altering corn to make it commercially resistant to glypho-sate. In 1991, RPA, DeKalb, and Calgene entered into an “Assignment and Assumption Agreement” (the “1991 Agreement”), in which RPA assumed Calgene’s rights and obligations under DeKalb’s 1985 Agreement with Calgene. RPA performed the molecular biology research work by creating various genetic constructs, initially with the CT7. Then, De-Kalb “transformed” corn cells by using the microprojectile bombardment method. This called for coating microprojectiles such as gold particles with the new DNA, firing the particles with a “gene gun” into a callus of embryonic maize cells on a petri dish, selecting and growing cells which had actually integrated the new DNA, testing in vitro, regenerating transformed cells into plants which, if fertile, would be crossed to create a second generation (the R-l generation) and testing R-l plants within the greenhouse and, then, in the field. At each stage, DeKalb tested the transformed cells and plants for glypho-sate resistance. Neither party had the capability to perform the other party’s role in this collaboration, and both roles were necessary in order to produce glyphosate resistant corn.
Under this collaboration, genetic material other than the CT-7 gene was transferred from one company to the other. On June 17, 1991, at the first joint meeting of RPA and DeKalb after the 1991 Agreement was signed, the companies agreed that any material transferred between the companies would be subject to a Confidentiality Agreement originally entered into by Calgene and DeKalb in 1984.
Experiments with CT7, however, continued to show that the CT7 gene did not impart sufficient glyphosate resistance in corn to be useful either as a selectable marker in vitro, or to impart sufficient glyphosate resistance to a transformed corn plant that it could withstand an application of glyphosate more than one-fourth that recommended as sufficient to kill easy to control weeds without being killed or stunted. (PTX 240 at DKB 040279-040281; PTX166 at DKB 056725.)
In 1988, Monsanto’s European patent application, PTX 1940, disclosed, among other things, that modifying maize EPSPS DNA to encode a protein with a mutation from Glycine to Alanine at position 101 would provide some glyphosate resistance in corn. (DeRose, Trial Tr. vol. I, 168-70 & vol. II, 312-17; Quatrano, Trial Tr. vol. VI, 1006-07; DTX 1940.)
The formal collaboration between De-Kalb and RPA lasted from June of 1991 to November of 1992 and included organized meetings of a Scientific Committee comprised of members from DeKalb and RPA. Throughout the collaboration, proposals were made by the Committee to determine what experiments should be done.
Consistent with Dr. Freyssinet’s statement at one of the final RPA/Calgene Committee meetings, RPA scientists Le-brun, Sailland and Freyssinet had the idea of using the mutation from the CT7 bacterial aroA gene (Proline Serine at the 101 position) and one of the three mutations from the B808 bacterial aroA gene (Threo-nine Isoleucine at the 97 position) in the amino acid sequence of a maize EPSPS gene from the cell line developed by Dr. Freyssinet. (Lebrun, Trial Tr. vol. Ill, 525-28, 54, 548^9 & vol. IV, 572-73.) The idea was that, perhaps, the mutations would be more successful at imparting gly-phosate resistance in RPA’s maize gene and, perhaps, the mutation from B808 would not be toxic to the maize gene. The gene was known as the “double mutant maize gene” (“DMMG”) because of the two mutations — Threonine Isoleucine at the 102 position and Proline Serine at the 106 position.
Throughout the RPA/DeKalb collaboration (June 1991 to November 1992), approximately four Scientific Committee meetings took place in which information on projects was shared between the companies. In November 1992, Dr. Freyssi-net attended the last of these four meetings. (Freyssinet, Trial Tr. vol. V, 733.) At that meeting, Dr. Freyssinet indicated that RPA would not put any further effort into molecular biology research for glypho-sate resistance but agreed to provide to DeKalb the new genetic material containing mutated EPSPS maize genes. (Freyssinet, Trial Tr. vol. V, 748.)
When Dr. Freyssinet returned from the meeting, he requested that Dr. Rick De-Rose, an RPA scientist, prepare various constructs using the single and double mutated maize genes to send to DeKalb. Dr. DeRose prepared and sent five different constructs to DeKalb in February 1993. Three included the new double mutant maize gene, DMMG (Threo Iso at 102 and Pro Ser at 106). Two included the single mutant (SMMG) (Gly Ala at 101) referred to earlier as the Monsanto mutation. (PTX 142 at DKB 040519; DeRose, Trial Tr. vol. I, 165-68, vol. II, 218-21 & vol. Ill, 419-20; Spencer, Trial Tr. vol VII, 1137-40.) The DNA constructs comprised either the DMMG or the SMMG along with other components variously included to target and enter the chloroplast and cut the portions — the “met”once in the chloroplast. Some included promoters. One of the constructs, RD-125, contained the DMMG, a transit peptide developed by RPA known as the “Optimized Transit Peptide” (“OTP”), a methionine (“met”) added at the cleavage site to promote stability, and a “stop” known in the art as NOS. Dr. Freyssinet and Dr. DeRose suggested that DeKalb also use a Rice Actin Promoter in connection with some of the constructs RPA provided. (Freyssinet, Trial Tr. vol. IV, 660-63.) All of the constructs were sent to DeKalb for the purpose of transforming corn cells and with the goal of creating glyphosate resistant corn.
DeKalb used the gene gun transformation process to insert the various constructs into the corn calli. The precise points at which the constructs integrate, if at all, into the corn genome are random and cannot be controlled. After the constructs have been introduced with the gene gun, the random but fixed integration of the DNA into the chromosome is the transformation event and each event is labeled individually for identification. The four “key” transformation events that resulted from insertion of RD-125 are labeled as: GA21, FI117, GJ11, and GG25.
The transformation events DeKalb created using RPA’s constructs were crossed with another corn line, creating a hybrid plant. (DeRose, Trial Tr. vol. II, 242.) In late 1993 and early 1994, in a greenhouse, DeKalb succeeded in growing transformed corn plants that contained RPA’s RD-125 construct and were resistant to Roundup® herbicide at potentially commercial levels. Those hybrid plants were then tested in the field in Hawaii in September 1994. The field tests showed that the corn plants resulting from the four transformation events (FI117, GA21, GG25, and GJ11) were resistant to glypho-sate when four times the normal commercial application rate was applied. GA21 was the event of choice after extensive testing with regenerates from these four transformation events. (Armstrong, Trial Tr. vol. Ill, 483-84; Quatrano; Trial Tr. vol. VI, 999 (“I think in almost all cases we end up putting a particular construct in to look at its expression, whether it is GA21 or FI117 or any other construct, that one has to look at a fairly large number of regenerates to actually see or to select out those that have a fairly high expression level, due primarily, we believe, to the position in which the DNA is inserted.”).)
The relevant facts concerning the patents that arose from these activities are discussed below.
III. INVENTORS
Patents are presumed to be valid and name the correct inventors. Canon Computer Sys., Inc. v. Nu-Kote Int’l Inc., 134 F.3d 1085, 1088-89 (Fed.Cir.1998). This presumption can only be overcome by clear and convincing evidence. See Applied Med. Res. Corp. v. U.S. Surgical Corp., 967 F.Supp. 867, 871 (E.D.Va.1997); Burroughs Wellcome Co. v. Barr Labs. Inc., 828 F.Supp. 1200, 1204 (E.D.N.C.1993) (citing Amax Fly Ash Corp. v. United States, 206 Ct.Cl. 756, 514 F.2d 1041, 1047 (Cl.Ct.1975)). However, a party may allege, as Plaintiff has here, that it was omitted from the named inventors under 35 U.S.C. § 256:
Whenever ... through error an inventor is not named in an issued patent and such error arose without any deceptive intention on his part, the Director may, on application of all the parties and assignees, with proof of the facts and such other requirements as may be imposed, issue a certificate correcting such error.
... The court before which such matter is called in question may order correction of the patent on notice and hearing of all parties concerned and the Director shall issue a certificate accordingly.
Id. Here, Plaintiff has called into question the omission of scientists it alleges are joint inventors on both the ’497 and the ’798 patents. The only procedural requirements for a correction of inventorship action in district court are notice and an opportunity to be heard. Id.; see also Stark v. Advanced Magnetics, Inc., 119 F.3d 1551, 1553 (Fed.Cir.1997). Both have been provided in this case. Therefore, the Court, if it is appropriate under the facts, may order correction of the patent. MCV, Inc. v. King-Seeley Thermos Co., 870 F.2d 1568, 1570 (Fed.Cir.1989) (“Section 256 ... explicitly authorizes judicial resolution of co-inventorship contests over issued patents ... ”).
With respect to joint inventorship, the Federal Circuit has said:
All that is required of a joint inventor is that he or she (1) contribute in some significant manner to the conception or reduction to practice of the invention; (2) make a contribution to the claimed invention that is not insignificant in quality, when that contribution is measured against the dimension of the full invention; and (3) do more than merely explain to the real inventors well-known concepts and/or the current state of the art.
Pannu v. Iolab Corp., 155 F.3d 1344, 1351 (Fed.Cir.1998). Joint inventors must also be working in collaboration. See Kimberly-Clark Corp. v. Proctor & Gamble Distrib. Co., 973 F.2d 911, 917 (Fed.Cir.1992) (holding that joint inventorship requires some level of collaboration). However, “[t]he question of whether a person is a joint inventor is fact specific, and no bright-line standard will suffice in every case.” Fina Oil & Chem. Co. v. Ewen, 123 F.3d 1466, 1473 (Fed.Cir.1997). Therefore, the facts of this case will be reviewed with respect to each patent to determine whether there is clear and convincing evidence that RPA’s five scientists meet the standard for joint inventorship.
An inventorship analysis, like an infringement analysis, begins with a construction of each asserted claim. See Markman v. Westview Instruments, Inc., 52 F.3d 967, 996 n. 7 (Fed.Cir.1995) (Mayer, J., concurring), aff'd, 517 U.S. 370, 116 S.Ct. 1384, 134 L.Ed.2d 577 (1996). After each asserted claim is construed, the second step is then to compare the alleged contributions of each asserted co-inventor with the subject matter of the properly construed claim to determine whether the correct inventors were named. Ethicon, Inc. v. U.S. Surgical Corp., 135 F.3d 1456, 1460 (Fed.Cir.1998). Thus, the construction of each of the patents will first be discussed, followed by a determination of whether joint inventorship is appropriate under the standard set forth above.
A. The %97 Patent
1. Claim Construction
The first patent for which RPA seeks to have its five scientists declared joint inventors is the ’497 patent or “Spencer patent”. For present purposes, the crucial claim in the ’497 patent is claim 46, which reads as follows:
A glyphosate resistant, hybrid maize plant comprising a chromosomally integrated expression cassette comprising (a) a modified maize EPSPS gene encoding an EPSPS protein having isoleucine at position 102 and serine at position 106 and (b) a promoter active in maize oper-ably linked to said EPSPS gene, wherein said hybrid maize plant comprises a transformation event selected from the group consisting of GA21, seed comprising said GA21 transformation event having been deposited as ATCC Accession Number 209033, FI117, seed comprising said FI117 transformation event having been deposited as ATCC Accession Number 209031,GG25, seed comprising said GG25 transformation event having been deposited as ATCC Accession Number 209032, and GJ11, seed comprising said GJ11 transformation event having been deposited as ATCC Accession Number 209030.
(’497 Patent, col.64,11.58 — col.65,11.4.)
The parties have agreed on the proper construction of this claim. Specifically, they have agreed to the following construction:
The phrase “[a] glyphosate resistant, hybrid maize plant” means a hybrid corn plant that provides the level of glypho-sate resistance provided by one of the four specifically identified transformation events. A hybrid corn plant is a cross of two different genotypes of corn, which are sometimes called the “parents” of the hybrid corn plant.
Because the four specifically identified transformation events already include (a) a modified maize EPSPS gene encoding an EPSPS protein having isoleucine at position 102 and serine at position 106 and (b) a promoter active in maize oper-ably linked to said EPSPS gene, the claimed hybrid corn plant must have as one of its parents one of the four transformation events discussed below. A transformation event is a plant or seed which has a specific DNA cassette in a specific location somewhere within the chromosome of the corn cells.
The specific transformation events are identified by the phrase “GA21, seed comprising said GA21 transformation event having been deposited as ATCC Accession Number 209033, FI117, seed comprising said FI117 transformation event having been deposited as ATCC Accession Number 209031, GG25, seed comprising said GG25 transformation event having been deposited as ATCC Accession Number 209032, and GJ11, seed comprising said GJ11 transformation event having been deposited as ATCC Accession Number 209030.” The seeds of the specific transformation events are made available to the public at the American Type Culture Collection, or “ATCC,” and the accession numbers identify where the seeds are indexed at the ATCC.
Because the parties have agreed to this construction, and because the construction appears consistent with the language of the claim, the Court adopts this construction in its entirety.
2. Application — Conception and Joint Inventorship
Conception has been called the “touchstone of inventorship.” Burroughs Wellcome Co. v. Barr Labs., Inc., 40 F.3d 1223, 1228 (Fed.Cir.1994). Courts have defined conception for the purposes of inventorship as:
‘... the formation in the mind of the inventor, of a definite and permanent idea of the complete and operative invention, as it is hereafter to be applied in practice.’ Hybritech, Inc. v. Monoclonal Antibodies, Inc., 802 F.2d 1367, 1376 (Fed.Cir.1986) (quoting 1 Robinson on Patents 532 (1890)). An idea is sufficiently ‘definite and permanent’ when ‘only ordinary skill would be necessary to reduce the invention to practice, without extensive research or experimentation.’ Burroughs Wellcome Co. v. Barr Labs., Inc., 40 F.3d at 1228.
Ethicon Inc., 135 F.3d at 1460.
DeKalb contends that since the ’497 patent is for the transformation events — i.e. the moment when the DNA cassette became fixed or inserted within the respective chromosomes of each of the four events — the RPA scientists could not be joint inventors because none of them could have had a definite and permanent idea of the complete and operative invention at the time of any contribution they may have made. The DNA inserts randomly, if at all, so no one could foretell prior to the event where an insertion point might be. (Spencer, Trial Tr. vol. VIII, 1101; Sail-land, Trial Tr. vol. VIII, 1203.) Specifically, whether it would confer glyphosate resistance and to what extent could not be determined until testing. (Spencer, Trial Tr. vol. VIII, 1102-03.) Nor could the plant’s fertility be immediately determined. Finally, DeKalb contends that in vitro resistance did not mean resistance for the whole plant and had never translated into sufficient resistance for a corn plant to withstand the amount of glypho-sate recommended to kill weeds. (Lebrun, Trial Tr. vol. Ill, 535; Armstrong, Trial Tr. vol. 111,492.)
The short answer to DeKalb’s contention is that, in the case of persons working jointly to solve a common problem as were the teams from RPA and DeKalb, different people may contribute in different ways and at different times toward a common conception. As the Federal Circuit observed in Fina Oil:
The issue of joint inventorship is governed by 35 U.S.C. § 116, which states, in relevant part:
When an invention is made by two or more persons jointly, they shall apply for a patent jointly and each make the required oath, except as otherwise provided in this title. Inventors may apply for a patent jointly even though (1) they did not physically work together or at the same time, (2) each did not make the same type or amount of contribution, or (3) each did not make a contribution to the subject matter of every claim of the patent.
This provision sets no explicit lower limit on the quantum or quality of inventive contribution required for a person to qualify as a joint inventor.. Rather, a joint invention is simply the product of a collaboration between two or more persons working together to solve the problem addressed. Burroughs Wellcome, 40 F.3d at 1227, 32 USPQ2d at 1919. The determination of whether a person is a joint inventor is fact specific, and no bright-line standard will suffice in every case.
Conception and inventorship are questions of law, reviewed de novo, that rest on underlying facts. See Sewall, 21 F.3d at 415, 30 USPQ2d at 1358.
Nonetheless, our precedent provides guidance as to what types of acts are, or are not, sufficient in quantum and quality to establish joint inventorship. One need not alone conceive of the entire invention, for this would obviate the concept of joint inventorship. However, a joint inventor must contribute in some significant manner to the conception of the invention. See Pro-Mold & Tool Co. v. Great Lakes Plastics, Inc., 75 F.3d 1568, 1575, 37 USPQ2d 1626, 1632 (Fed.Cir.1996) (citing Sewall, 21 F.3d at 415, 30 USPQ2d at 1358-59). As such, “each inventor must contribute to the joint arrival at a definite and permanent idea of the invention as it will be used in practice.” Burroughs Wellcome, 40 F.3d at 1229, 32 USPQ2d at 1921.
If a person supplies the required quantum of inventive contribution, that person does not lose his or her status as a joint inventor just because he or she used the services, ideas, and aid of others in the process of perfecting the invention. See Shatterproof Glass Corp. v. Libbey-Owens Ford Co., 758 F.2d 613, 624, 225 USPQ 634, 641 (Fed.Cir.1985). However, those others may also in appropriate circumstances become joint inventors by their contributions. In addition, a person is not precluded from being a joint inventor simply because his or her contribution to a collaborative effort is experimental. See Burroughs Wellcome, 40 F.3d at 1229, 32 USPQ2d at 1921.
The basic exercise of the normal skill expected of one skilled in the art, without an inventive act, also does not make one a joint inventor. See Sewall, 21 F.3d at 416, 30 USPQ2d at 1359. Therefore, a person will not be a co-inventor if he or she does no more than explain to the real inventors concepts that are well known and the current state of the art. See Hess, 106 F.3d at 981, 41 USPQ2d at 1787. The case law thus indicates that to be a joint inventor, an individual must make a contribution to the conception of the claimed invention that is not insignificant in quality, when that contribution is measured against the dimension of the full invention.
In cases where conception does not occur until there has been a reduction to practice, a person who has contributed a significant, inventive act does not lose joint inventor status because the contribution was made prior to conception. As the Fina Oil court observed:
Conception and reduction to practice of the entire claimed invention may be relevant to establish that a first person conceived of an invention before another person entered the scene, and that the first person is therefore the sole inventor. However, the doctrine cannot be used, as the district court did here, to show that because the first person did not conceive or reduce to practice the entire claimed invention, he or she did not at least contribute in some significant way to the ultimate conception.
The advisory jury found that each of the five RPA scientists should be named as inventors of the ’497 patent. For the reasons which follow, the Court agrees with the advisory jury’s determination.
The claim construction agreed upon by the parties comprises at least the following limitations: (1) A hybrid maize plant which (2) is resistant to glyphosate and which (3) contains a modified maize EPSPS gene encoding an EPSPS protein having Isoleu-cine at position 102 and Serine at position 106 in addition to (4) a promoter active in maize operably linked to the modified EPSPS gene. The plant (5) must have as a parent one of the four specific transformation events: GA21, FI117, GG25, or GJ11.
The evidence clearly and convincingly shows that beginning in 1990, RPA and DeKalb engaged in a collaborative effort to create genetically engineered, glyphosate resistant corn. (Orozco, Trial Tr. vol. Ill, 473.) As observed earlier, each brought a special expertise to their project: RPA had an expertise in identifying and synthesizing DNA constructs which had the potential to lessen the binding of glyphosate in maize EPSPS enzymes and to permit the enzyme to continue its vital function in the plant’s production of its own food. De-Kalb had the transformation process of Drs. Lundquist and Walters and the consequent ability to bombard embryonic corn cells with RPA’s genetic material and regenerate transformed plants containing that genetic material. The purpose of the collaboration was to create hybrid corn plants made glyphosate resistant by incorporating modified DNA encoding EPSPS enzymes which could perform the function of catalyzing the synthesis of EPSP in the presence of glyphosate.
Although RPA determined sometime in 1992 to suspend research efforts toward isolating new DNA constructs, it had already originated and synthesized maize DNA encoding a modified maize EPSPS protein with Isoleucine at 102 and Serine at 106 (the “DMMG”). It had identified and constructed several promoters operable in maize and, particularly active in the faster growing areas of the plant — tips of stems and roots — where glyphosate concentrates most. (Lebrun, Trial Tr. vol. Ill, 517-18.) And, RPA had originated and constructed the OTP which was more effective in delivering precursor EPSPS to the maize chloroplast, transporting the EPSPS across the membrane wall, and being cleaved at the precise site than any other transit peptide in the literature at that time. (Lebrun, Trial Tr. vol. Ill, 508-16.)
Pursuant to their agreement, in February 1993, RPA sent several constructs containing RD-125 (the DMMG with a Met and the OTP) linked to several promoters and other regulatory elements. It was those constructs which Michael Spencer of DeKalb used in the particle gun in the Spring and Summer of 1993 to create the transformation events claimed in the ’497 patent. Those events, following selection, were tested in vitro for glyphosate resistance, regenerated into plants, tested in the laboratory, crossed with another line to create the R1 generation, then taken into the field for testing with glyphosate. (Spencer, Trial Tr. vol. VIII, 1104-20.)
After the testing of the plants in a greenhouse, on February 18, 1994, DeKalb reported the following to RPA:
[W]e have not only demonstrated that we can use the mutant maize EPSPS gene as a selectable marker in maize, but we have now demonstrated tolerance in transgenic plants in the greenhouse to up to four times the field application recommended by Monsanto for tolerant corn! We will repeat these experiments in the field in the summer of 1994. It is obvious from these results that the mutant maize gene has been the key to success.
(PTX 240 at DKB 040277.)
During the subsequent field trials conducted in September 1994, each showed the ability not to be harmed from a 16 ounces per acre application of glypho-sate — -the recommended amount for killing weeds. GG25 (DMMG + OTP + maize histone promoter) and GJ11 (DMMG + OTP + 35S/Arabidopsis histone promoter) appeared as healthy at 64 ounces per acre as plants which had not been sprayed at all. (Spencer, Trial Tr. vol. VIII, 1162; PTX 307 at DKB 040526.) At 64 ounces, FI17 (DMMG + OTP + rice actin promoter) became “somewhat yellow”, a ranking of 2 on a scale in which 3 was “yellow, twisted”, 4 was “wilted, stunted” and 5 was “dead”. GA21 (DMMG + OTP + rice actin promoter), at 64 ounces, graded 2.5. (PTX 307 at DKB 040526.)
At that point conception was complete: hybrid plants — the offspring of two different genotypes, one parent of each being one of the four claimed transformation events, each containing a DNA cassette with a modified maize EPSPS gene encoding an EPSPS protein having Isoleucine at position 102 and Serine at position 106, and a promoter active in maize operably linked to the modified EPSPS gene — had demonstrated glyphosate resistance.
It is true that conception was completed without RPA or any of its scientists being informed of the successful field trials. DeKalb’s proceeding with further testing and crossing with elite lines to commercialize “Roundup Ready®” corn without informing RPA was the subject of a previous jury finding that DeKalb had committed fraud, breached the collaboration agreement, and been unjustly enriched. See Rhone-Poulenc Agro, S.A. v. DeKalb Genetics Corp., 272 F.3d 1335 (Fed.Cir.2001) (vacated and remanded for reconsideration of the amount of punitive damages in light of State Farm Mut. Auto. Ins., v. Campbell, 538 U.S. 408, 123 S.Ct. 1513, 155 L.Ed.2d 585 (2003) by DeKalb Genetics Corp. v. Bayer CropScience, S.A., 538 U.S. 974, 123 S.Ct. 1828, 155 L.Ed.2d 662 (2003), opinion modified and reinstated by Rhone-Poulenc Agro, S.A. v. DeKalb Genetics Corp., 345 F.3d 1366 (Fed.Cir.2003), cert. denied, DeKalb Genetics Corp. v. Bayer CropScience, S.A., 540 U.S. 1183, 124 S.Ct. 1423, 158 L.Ed.2d 86 (2004)). That, however, is a non-issue since neither the statute nor the cases relating to joint inventorship requires the simultaneous presence or awareness of all who have contributed significantly toward conception when the last piece of the conception puzzle slips into place.
It is beyond serious question that RPA scientists contributed genetic constructs which, when inserted, created the glypho-sate resistance possessed by each of the transformation events. It is undisputed that RPA scientists provided the “modified maize EPSPS gene encoding an EPSPS protein having [l]soleucine at position 102 and [S]erine at position 106” as well as two “promoter(s) operably linked to said EPSPS gene” claimed in the ’497 patent. (PTX 142 at DKB 040519; Spencer, Trial Tr. vol. VIII, 1127, 1139.) DeKalb argues, however, that none of the RPA scientists made a contribution of inventive significance, but rather were merely explaining and practicing the state of the art. Thus, the next step is a consideration of the specific contributions of each of the five and a determination of whether that person made an inventive contribution which was not insignificant when measured against the dimension of the full invention.
Dr. Georges Freyssinet was the RPA glyphosate resistance project leader. Dr. Freyssinet attended the Scientific Committee meetings with both Calgene and De-Kalb where attendees discussed ideas and research plans for improving resistance. In 1989, at a Scientific Committee meeting with Calgene, Dr. Comai discussed the possibility of mutating a wild type bacterial EPSPS gene by combining the Pro Ser, 101, mutation from the CT7 aroA gene with the Threo Iso, 97, mutation from the B808 randomly mutated bacterial gene. (Comai, Trial Tr. vol. v, 863-68; DTX 1477 at RPA 031675, 031685.) At the meeting, Dr. Freyssinet proposed that RPA would mutate a maize gene. (Comai Trial Tr. vol V, 893; DTX 1477 at RPA 031676.)
Although using plant genes for muta-genesis had been discussed from time to time within Calgene and debated within the Scientific Committee meetings with RPA, Dr. Comai never made a concrete proposal to do so, electing instead to continue research with the Salmonella gene. (Comai, Trial Tr. vol. V, 877, 879-81, 888, 889.) It was later determined that the Threo Iso, 97, mutation was toxic to the mutagenized bacteria and Calgene never performed the site directed mutagenesis to encode both the Threo Iso, 97 and the Pro Ser, 101 substitutions in a single aroA gene. (Freyssinet, Trial Tr. vol IV, 619— 21; PTX 1431 at CAL 004228-004246; Le-brun Trial Tr. vol. IV, 573.) Further, transformed tobacco plants with the Threo Iso, 97 substitution had underdeveloped roots, leading to the conclusion that the protein was not stable. (Freyssinet, Trial Tr. vol. TV, 621-22.)
At RPA in 1986, a focus had been on increasing glyphosate resistance in maize by developing a line that produced an overabundance of EPSPS enzymes. The cells of this line were more tolerant than wild type maize. In 1989 it was decided by the project team — Drs. Freyssinet, Lebrun, Leroux and Sailland — to use cells preserved from this line for site directed mutagenesis. Starting in late 1989, Michel Lebrun spent about one year isolating the EPSPS gene from the cDNA. (Freyssinet, Trial Tr. vol. IV, 613, 626-28.) The gene was then sequenced and it was determined that there were three nucleotide and three amino acid changes from that published by Monsanto in 1988. (Lebrun, Trial Tr. vol. Ill, 563-64; DTX 1620 at RPA 016933.) At a meeting in Lyon, a decision was made by the four team members to combine, two by two, the Threo Iso, Pro Ser, and Gly Ala mutations in the conserved region around amino acid position 100. They decided to start by making eight variants, one with the specific mutations resulting in Threo Iso, 102, and Pro Ser, 106 (the “DMMG”), even though the Threo Iso substitution had proven toxic when made in bacteria. They also decided to make a single mutation resulting in a Gly Ala, at position 101 and another single mutation with a Pro Ser at position 106. (Freyssi-net, Trial Tr. vol. IV, 627; Lebrun, Trial Tr. vol. IV, 572, 573; DTX 1944 at RPA 008138.)
It was, therefore, the idea of Drs. Freys-sinet, Lebrun, Sailland and Leroux to combine the mutations resulting in Threo Iso, 102, and Pro Ser, 106, in a maize cell. While Monsanto had mutagenized a maize gene, made hundreds of thousands of mutations in EPSPS genes, and a number of changes in the 101,102, 105 and 106 region of plant genes, it had never combined the Threo Iso, 102, and Pro Ser, 106. (Pad-gette, Trial Tr. vol. IV, 581, 584-85.) While Dr. Comai had broached, both during and prior to the collaboration with RPA, the advisability of using plant genes, the possibility had never matured beyond debate. Also, while Dr. Comai had suggested the combination in bacteria of Threo Iso, 97, and Pro Ser, 101 — the equivalent amino acid positions in Salmonella to 102 and 106 in maize, the combination was not made after it was determined that the substitution of Isoleucine at position 97 had a toxic effect on the host bacteria.
The DMMG was essential to glyphosate resistance in each of the transformation events: it had the physical structure to block the glyphosate molecule while allowing entrance of the PEP, resulting in an EPSPS enzyme able to perform its life sustaining function in the presence of considerable amounts of glyphosate.
Drs. Freyssinet, Leroux and DeRose originated and synthesized the maize hi-stone promoter which was “operably linked” to the DMMG in GG25. Dr. Freys-sinet and Dr. Leroux also originated and synthesized the 35S/Arabidopsis histone promoter which was “operably linked” to the DMMG in GJ11. The promoter controls the transcription phase by attracting the RNA polymerase and it also directs where in the plant the gene will be expressed. It was important to have a promoter that would produce a lot of EPSPS, especially in the areas of the corn plant where glyphosate accumulates — tips of stems and roots. (Lebrun, Trial Tr. vol. Ill, 516-18; DeRose, Trial Tr. vol. 1,141-42,146.)
Drs. Lebrun, Leroux and Sailland originated and synthesized the OTP, the “optimized transit peptide”, which targets the chloroplast for the EPSPS precursor protein and accomplishes entry through the chloroplast wall before being cleaved from what then becomes the mature EPSPS protein or enzyme. DeKalb contends that the OTP was a prior art element and should not be considered an inventive contribution to these transformation events. The OTP, however, had been sent to De-Kalb in 1991 as an integral portion of a construct (with the 35S/Arabidopsis hi-stone promoter and the CT7) as a part of the RPA/DeKalb joint effort toward creating glyphosate resistant corn. (PTX 53 at DKB 009830.) And, Dr. Lebrun had discussed the OTP with DeKalb scientists at a Scientific Committee meeting in October, 1991. (PTX 55 at DKB 026454; Lebrun Trial Tr. vol. Ill, 519.) While Drs. Le-roux, Lebrun and Sailland applied for a French patent on the OTP in March of 1991, the OTP was not disclosed to the public until September 11, 1992. (DTX 1257.) Because they were the inventors and were working collaboratively with De-Kalb, they would not have been simply explaining prior art when the OTP was sent to DeKalb with the DMMG in February, 1993. In re Katz, 687 F.2d 450 (Oust. & Pat.App.1982); see also Pannu, 155 F.3d at 1344 (holding Pannu was at least a co-inventor because he and the other purported inventor had worked collaboratively and Pannu had conceived of significant aspects of the invention although he had discussed his ideas with others more than a year earlier than he did with the other purported inventor).
Considering the extensive but unavailing efforts of other researchers in the field to modify DNA and alter the structure of the EPSPS enzyme so that it would block the glyphosate molecule, yet allow the PEP to bond with the shikimate and form EPSP, there is no doubt that the RPA constructs were the most significant genetic development in the effort to create glyphosate resistant maize. It is determined that each of the contributions enumerated above are inventive and significant when compared to the invention as a whole. Each was vital to the creation of glypho-sate resistance in at least one of the four transformation events and each of the five individual RPA scientists should be added as co-inventors on the ’497 patent.
It is further determined, however, that the following contributions cited by RPA do not rise to the level of inventive significance.
Dr. Freyssinet’s informing DeKalb at the first Scientific Committee meeting in June, 1991 about the probable efficacy of the rice actin promoter in maize, (see DTX 290 at DKB 026532), was an explanation of the state of the art, not an inventive contribution. See Hess v. Advanced Cardiovascular Sys. Inc., 106 F.3d 976, 981 (Fed.Cir.1997).
Dr. DeRose’s addition of the Met to the OTP-DMMG junction and his modification of the OTP by adding restrictor sites for easier addition or removal of promoters certainly contributed to the probable effectiveness of the constructs but constituted practicing the state of the art. There is no showing that either were inventive contributions. As he testified, the literature at the time reported the effectiveness of a Methionine in prolonging the stability of proteins. (DeRose, Trial Tr. vol. II, 222-23.) There is no evidence to support a finding by clear and convincing evidence that adding restrictor sites was novel and there was evidence that it was not. (Spencer, Trial Tr. vol. VIII, 1137-38.)
Nor does the evidence support a finding of an inventive aspect in Dr. DeRose’s combination of elements for the various constructs sent in February, 1993. According to his testimony, the ideas for combining OTP with the DMMG and, then, with different promoters were attributable variously to Drs. Freyssinet, Lebrun, Le-roux and Sailland. (DeRose, Trial Tr. vol. II, 221, 222, 226.)
Similarly, while Dr. Lebrun’s contribution of isolating the maize EPSPS gene was central to obtaining the DNA to be mutagenized, there is no showing that it was more than a state of the art undertaking.
B. The ’798 patent
1. Claim Construction
The second patent for which RPA seeks to have its five scientists declared joint inventors is the ’798 patent. Claim 1 of the ’798 patent reads:
A fertile transgenic Zea mays plant containing an isolated heterologous DNA construct encoding EPSP syn-thase wherein said DNA construct is expressed so that the plant exhibits resistance to normally toxic levels of gly-phosate, wherein said resistance is not present in a Zea mays plant not containing said DNA construct, and wherein said DNA construct is transmitted through a complete normal sexual cycle of the transgenic plant to the progeny generation.
(’798 Patent, col.26,11. 15-23.) The parties stipulated to all of the claim construction except as to how to construe the following language in the claim: “the plant exhibits resistance to normally toxic levels of gly-phosate, wherein said resistance is not present in a Zea mays plant not containing said DNA construct.” The Court ultimately construed that language and instructed the advisory jury that the terms effectively meant that an amount of glyphosate normally sufficient to kill a non-transgenic corn plant would have no effect upon the transgenic plant. This, then, was construed as the transformed plant having total resistance or immunity to an amount of glyphosate which would normally kill non-transgenic corn. The advisory jury found that the five RPA scientists had contributed to the conception of: 1) fertile transgenic corn containing DNA constructs encoding non-baeterial mutated plant EPSP synthases; and 2) fertile transgenic corn containing DNA constructs encoding EPSP synthases that provide glyphosate resistance to corn.
After further consideration, the Court believes it improperly construed the claim at issue and, therefore, improperly instructed the advisory jury. This section discusses the construction read to the jury, the construction now adopted, the basis for the Court’s interpretations and the effect on the claims of the plaintiffs to be added as inventors on the ’798 patent.
a.
The procedure for claim construction is well known. The first step is an examination of the intrinsic evidence which includes: (1) the language of the claims themselves; (2) the patent’s specification; and (3) the patent’s prosecution history. Markman, 52 F.3d at 979. This intrinsic evidence is the “most significant source of the legally operative meaning of the dis-ited claim language.” Vitronics Corp. v. Conceptronic, Inc., 90 F.3d 1576, 1582 (Fed.Cir.1996).
Thus, a district court should “[f]irst ... look to the words of the claims themselves, both asserted and nonasserted, to define the scope of the patented invention.” Id. The court is then to look to the specification of the patent which contains a written description of the invention which must be clear and complete enough to enable those of ordinary skill in the art to make and use the invention. Id. Finally, the prosecution history, often referred to as the “file wrapper,” should be considered by the court. Id. The prosecution history contains the complete record of all of the proceedings before the Patent and Trademark Office. The prosecution history is often of “critical signification in determining the meaning of the claim” because it includes any express representations made by the applicant regarding the scope of the claims. Id.; see also Southwall Tech. Inc. v. Cardinal IG Co., 54 F.3d 1570, 1576 (Fed.Cir.1995) (“The prosecution history limits the interpretation of claim terms so as to exclude any interpretation that was disclaimed during the prosecution.”) (citations omitted). However, “[a]lthough the prosecution history can and should be used to understand the language used in the claims, it ... cannot ‘enlarge, diminish, or vary’ the limitations in the claims.” Markman, 52 F.3d at 980 (quoting Goodyear Dental Vulcanite Co. v. Davis, 102 U.S. 222, 227, 12 Otto 222, 26 L.Ed. 149 (1880)).
When the intrinsic evidence fails to resolve the ambiguity in the disputed term, extrinsic evidence may be considered. See, e.g., Pall Corp. v. Micron Separa tions, Inc., 66 F.3d 1211, 1216 (Fed.Cir.1995) (“Extrinsic evidence may also be considered, if needed to assist in determining the meaning or scope of technical terms in the claims.”) (citations omitted, emphasis added); Vitronics Corp., 90 F.3d. at 1583 (explaining that it is only proper to rely on extrinsic evidence if the analysis of the intrinsic evidence fails to resolve the ambiguity in the disputed claim term). Extrinsic evidence includes evidence outside of the patent and its prosecution history, such as expert testimony, the inventor’s testimony, dictionaries, and learned treatises. Markman, 52 F.3d at 980-81 (suggesting this is not an exhaustive list and that any evidence that is helpful may be admitted as extrinsic evidence). However, if this evidence is necessary, it can only be used by the court to aid its understanding of the patent, and not to vary or contradict the terms as used in the claims. See id. at 981; Vitronics Corp., 90 F.3d at 1583 (“Allowing the public record to