Opinion
Case No. 99-CV-2668 H (AJB)
August 2, 2002
Gen-Probe Incorporated ("Gen-Probe") initiated this declaratory judgment action against Vysis, Inc. ("Vysis") in December 1999. Gen-Probe alleged non-infringement, invalidity and unenforceability of Vysis' U.S. Patent No. 5,750,338 (the "`338 patent")
The trial in this case commenced on May 7, 2002. The parties presented their evidence from May 7, 2002 to May 21, 2002. On May 22, 2002, the jury returned its special verdict, including an advisory verdict on the equitable issues of inequitable conduct and prosecution laches. Pursuant to the jury's special verdict, the Court entered a final judgment of non-infringement and invalidity based on obviousness and lack of enablement on May 23, 2002. The Court however reserved its judgment on the equitable issues.
Pursuant to the parties' requests, the Court deemed the parties' motion for judgment as a matter of law or for a new trial to be renewed. On June 17, 2002, Vysis and Gen-Probe filed their respective papers on their renewed motions. On July 1, 2002, the parties submitted their respective oppositions. On July 9, 2002, Gen-Probe and Vysis filed their reply papers. On July 10, 2002, they submitted supplemental lodgments to support their motions.
On August 2, 2002, the Court head a telephonic hearing on the pending motions. At that hearing, Stephen Swinton, Christopher Jaczko, and R. William Bowen appeared on behalf of Gen-Probe. Charles Lipsey, Thomas Banks, Scott Burwell, Jeffrey Weinberger, and Ted Danes appeared on behalf of Vysis. Christine Gritzmacher, Dan Kachian and Peter Shearer from (Gen-Probe, and Norval Galloway from Vysis, also attended the hearing telephonically.
Having considered the controlling law, the evidence presented at trial, and the parties' arguments, the Court declines to modify the jury's verdict as to non-infringement and invalidity, rules in favor of Vysis on Gen-Probe's equitable and unfair competition claims, and denies Vysis' motion for anew trial.
FACTUAL AND PROCEDURAL BACKGROUND
I. The Complaint
On December 22, 1999, plaintiff Gen-Probe filed a complaint for declaratory relief and unfair competition related to a patent and license agreement with the defendant Vysis. Gen-Probe is a San Diego-based biotechnology company that develops and markets nucleic acid tests. One of its main products is a nucleic acid test used in screening for the human immunodeficiency virus ("HIV") and the hepatitis C virus ("HCV").
Declaratory defendant Vysis is a Delaware corporation with its principal place of business in Illinois. Vysis owns the rights to the `338 patent, which issued on May 12, 1998 and covers certain nucleic acid test methods. For the purpose of this case, Vysis is a successor in interest to Gene-Trak Systems (Trial transcript ("Tr.") Vol. II at 501:2-501:4) and, until the Fall of 2001, was a subsidiary of Amoco Corporation. In the fall of 2001, Abbott Laboratories acquired Amoco's interests in Vysis.
Following the convention that the parties used throughout this case and trial, the Court will refer to Vysis, Gene Trak and Amoco by the singular reference to "Vysis," unless the identity of the particular company is important to the discussion.
Gen-Probe and Vysis share a long history of adverse litigation. (Tr. Vol. II at 358:2-362:11). After years of legal action against each other, the parties attempted to resolve their differences in the late 1990's. (Tr. Vol. II at 366:10-369:4). As part of a global settlement that resolved those litigations, Vysis granted Gen-Probe a license to the `338 patent. (Tr. Vol. II at 369:5-370:19). however, after further evaluation, Gen-Probe believed that the `338 patent was invalid, unenforceable and not infringed by its products. (Tr. Vol. II at 369:15-369:20 and 370:20-371:24). Although it continues to pay the required quarterly royalties, Gen-Probe filed this declaratory action in December 1999. (Tr. Vol. V at 990:21-991:7).
The Court has provided further details on the companies' relationship and the history of the license in the order denying Vysis' motion to dismiss for lack of subject matter jurisdiction. (Mar. 12, 2002 Order [Docket #334]).
On March 13, 2001, Gen-Probe filed its second amended complaint raising the same grounds as its original complaint. Specifically, Gen-Probe asserts the following causes of action: (1) non-infringement of the `338 patent; (2) invalidity of the `338 patent; (3) declaratory relief; (4) unfair competition; and (5) unenforceability of the `338 patent.
II. The `338 Patent
The `338 patent relates generally to methods for use in nucleic acid diagnostics. The `338 patent describes methods by which nucleic acids may be "captured" onto solid supports and "amplified," so that small quantities of nucleic acids may be then detected by the probes.
A discussion of certain scientific facts is necessary to facilitate an understanding of the patent. Each cell in an organism contains information-encoding elements, called genes, that direct the functioning of the cell, the production of specific proteins, and the development of the organism. (`338 patent, col. 2. ln. 35-37; Tr. Vol. I at 160:20-160:22). Genes are comprised of molecules of deoxyribonucleic acid ("DNA"). (`338 patent, col. 2, ln. 20-21).
DNA consists of two long chains that wrap around each other in the shape of a double-stranded spiral helix. (`338 patent, col. 2, ln. 21-22; Tr. Vol. I at 160:2-160:6). The twisted DNA strands are held together by hydrogen bonds between molecules called nucleotides. (`338 patent, col. 2, In. 24-27 and 33-35). There are only four different nucleotides in a DNA chain, each containing one of the bases adenine ("A"), guanine ("G"), cytosine ("C") and thymine ("T"). (`338 patent, col. 2, in. 22-24; Tr. Vol. I at 160:13-160:19). Because of the nucleotides' chemical structure, A will only pair with T, and C will only pair with G. (`338 patent, col. 2, In. 27-30; Tr. Vol. I at 161:6-161:17). Given this strict complementary pairing, the order of the nucleotides on one side of a DNA strand determines the order on the other side of the strand. (`338 patent, col. 2, In. 33-35; Tr. Vol. I at 161:12-161:17). In a gene, the order of these four nucleotides constitute the cell's genetic code and encodes for the sequence of a particular protein.
DNA directs cells to make proteins through a two-step process of transcription and translation. (Tr. Vol. I at 162:1-162:5; see also Mycogen Plant Sci., Inc. v. Monsanto Co., 243 F.3d 1316, 1323 (Fed. Cir. 2001) (providing a detailed discussion of the biological process of transcription and translation)). First, transcription occurs. Mycogen, 243 F.3d at 1323. During transcription, information is transferred from the DNA sequence of nucleotides by copying a specific DNA region into a chemically and functionally different type of molecule called ribonucleic acid ("RNA"). (Tr. Vol. 162:8-162:13; see also Mycogen, 243 F.3d at 1323). RNA is a long single strand of linked nucleotides similar to DNA, with one major difference: RNA contains the base uracil ("U") in place of thymine. (Tr. Vol. 162:14-162:21; see also Mycogen, 243 F.3d at 1323). In transcription, specific nucleotide sequences on the DNA determine where the RNA copy begins and ends. See Mycogen, 243 F.3d at 1323. The second step in protein synthesis is translation. Id. During translation, the cell mechanisms translate the RNA nucleotide sequence into the amino acid sequence of the corresponding protein, Id.
The `338 patent relies on these basic scientific facts in teaching methods to "target capture" and "amplify" target DNA and RNA molecules. "Target capture" techniques are used in nucleic acid methods to isolate a particular nucleic acid of interest prior to detection or other steps. (`338 patent, 28 col. 1, ln. 23-29). In target capture methods, the target nucleic acid is bound to a solid support, such as a filter, particle, or bead, that allows the target to be removed from the sample in which it was originally contained. (Id., col. 4, In. 18-24; Tr. Vol. I at 173:14-175:17).
After target capture, it is sometimes necessary to achieve a detectable level of target organisms in a sample by increasing the target organism s nucleic acid through a "nucleic acid amplification" process. (`338 patent, col. 9, ln. 42-53). This "amplification" process uses polymerase enzymes and primers. (E.g., id., col. 31, ln. 25-54).
This amplification process operates analogously to the way DNA makes copies of itself through a "replication"process. (Tr. Vol. III at 534:12-534:16; Declaration of Dr. Joseph O. Falkinham in Support of Gen-Probe's Motion for Partial Summary Judgment, filed on April 30, 2001 ("Falkinham Decl"), at ¶ 6). During replication, the original DNA serves as a template for the newly synthesized version. (Id). The enzyme "DNA polymerase" carries out the DNA replication process by using the specific chemical attraction between nucleotides as a foundation for faithful duplication. (Tr. Vol. III at 454:21-454:25; Falkinham bed., at ¶ 7). To initiate replication, DNA polymerases must recognize and bind to specific locations in the DNA. (Tr. Vol. III at 551:4-551:25; Tr. Vol. IV at 727:13-727:23; Falkinham Decl., at ¶¶ 8-9). Those specific locations are marked by a very short sequence complementary to the template strand. (Tr. Vol. IV at 656:15-657:12; Falkinham Decl., at ¶ 8). This short sequence of complementary nucleic acid is called a "primer" strand and the DNA polymerase absolutely requires a primer strand to start replication. (Tr. Vol. IV at 653:23-654:14 and 658:7-660:3; Falkinham Decl., at ¶ 9).
The Court has used the declarations of experts that the parties have submitted to understand the technology involved in this case, but not to construe the claims. The use of expert testimony and declarations for the sole purpose of understanding the technology is permissible.Pitney Bowes, Inc. v. Hewlett-Packard Co., 182 F.3d 1298, 1309 (Fed. Cir. 1999) ("Although the patent file may often be sufficient to permit the judge to interpret the technical aspects of the patent properly, consultation of extrinsic evidence is particularly appropriate to ensure that his or her understanding of the technical aspects of the patent is not entirely at variance with the understanding of one skilled in the art.").
Similarly to DNA replication, an enzyme called RNA polymerase catalyzes the synthesis of RNA during transcription. (Tr. Vol. III at 533:23-534:5 and 539:22-540:10; Declaration of Dr. Kary B. Mullis in Support of Gen-Probe Inc.'s Motion for Partial Summary Judgment of Non-Infringement under The Doctrine of Equivalents ("Mullis Decl."), at ¶ 11). Transcription begins when RNA polymerase binds to a specific starting sequence called the "promoter" sequence on the DNA. (Tr. Vol. 539:25-540:10; Mullis Decl., at ¶ 14). Differently from DNA polymerase, RNA polymerase does not need a primer to initiate replication; it only needs a promoter sequence. (Tr. Vol. I at 180:16-180:21; Tr. Vol. VI at 1274:25-1275:6; Mullis Decl., at ¶ 14). Once bound, the RNA polymerase joins the ribonucleotide bases of the gene based on their complementarity to the template DNA sequence, and continues to synthesize the growing RNA chain until it reaches a termination site on the DNA where the enzyme releases the completed messenger RNA copy of the gene. (Tr. Vol. I at 180:22-181:14; see Mullis Decl., at ¶ 14.). The `338 patent discloses amplification methods using replication via DNA polymerase or transcription by RNA polymerase. (E.g., `338 patent, col. 31 ln. 24 to col. 32 ln. 7).
As issued, the `338 patent contains seven independent claims: claims 1, 7, 19, 20, 27, 28, and 34. Each of these claims is generally directed to a method of, or kit for, capturing the target polynucleotide (i.e., binding a support to the target polynucleotide and substantially separating the support and bound target from the sample) and "amplifying" it. Each independent claim contains the target capture steps and the "amplifying" limitation For example, claim 1 — the broadest claim — provides:
A method for amplifying a target polynucleotide contained in a sample comprising the steps of:
(a) contracting the sample with a first support which binds to the target polynucleotide;
(b) substantially separating the support and bound target polynucleotide from the sample;
(c) amplifying the target polynucleotide.
Steps (a) and (b) jointly disclose the "target capture" step.
The `338 patent specification sets forth seven examples of the methods taught by the inventors. (`338 patent, col. 24 ln. 14 to col. 32 ln. 25). The parties do not dispute that the first three examples refer only to methods of target capture alone, while examples four through seven disclose the combination of target capture and methods of amplification. (Defendant's Statement of Disputed Facts in Opposition to Plaintiff's Motion for Partial Summary Judgment, filed on May 25, 2001 ("May 25, 2001 Statement of Facts"), at Fact 3).
III. Gen-Probe's Transcription Mediated Amplification Method
Gen-Probe's HIV-1/HCV Assay detects small quantities of human immunodeficiency virus ("HIV") and hepatitis C virus ("HCV") in blood by capturing the viral nucleic acids from a sample of blood and amplifying them. (Tr. Vol. I at 153:2-155:21; Declaration of Dr. Matthew Longiaru filed in Support of Gen-Probe's Motion for Partial Summary Judgment of No Literal Infringement, filed April 30, 2001 ("Longiara Decl."). at ¶ 5).
Gen-Probe's accused assay includes a capture step. (Tr. Vol. I at 150:2-150:8, 154:22-155:24, and 172:23-173:3). For the infringement analysis, Gen-Probe does not strenuously dispute that the `338 patent encompasses that capture step. (Tr. Vol. VII at 1345:10-1345:24). The parties' disagreement centers on the amplification step. Thus, a discussion of the assay's amplification approach is necessary.
The assay incorporates Gen-Probe's transcription mediated amplification ("TMA") technology to amplify the captured viral nucleic acid. (Tr. Vol. I at 152:8-152:19; Longiaru Del., at ¶ 5). The first step of the amplification process involves the binding of a primer to the viral RNA. (Tr. Vol. 177:9-177:24). The TMA amplification process employs sequence-specific primers, which are designed to bind only to specific sequences of interest in the target HIV and HCV nucleic acid. (Tr. Vol. 1 at 177:13-177:25; Longiaru Decl., at ¶ 6). Amplification of captured nucleic acid would thus occurs only if the specific primers find and bind to their respective specific target sequences. (Tr. Vol. I at 178:15-180:12; Longiaru Decl., at ¶ 6).
The primers used in Gen-Probe's TMA process are "specific primers." (Tr. Vol. 177:13-177:25; May 25, 2001 Statement of Facts, at Facts 27-28 [Docket #121]). These "specific" primers are carefully designed to bind only to a pre-selected nucleic acid sequence of a particular target organism, and precisely define the starting point of DNA replication. (Tr. Vol. I at 177:13-177:19 and 179:13-179:15; Mullis Decl., at ¶ 13). Using the primer, DNA polymerase then add one base at a time in a reaction referred to as "primer extension." (Tr. Vol. I at 178:19-180:2; Mullis Decl., at ¶ 13).
Alternatively, scientists may also use "non-specific," or "random," primers. (Tr. Vol. I at 164:4-164:22; Falkinham Decl., at ¶ 12). Those non-specific primers usually have shorter sequences, often six nucleotides in lengths, that are likely to complementarily bind to some unspecified location on the DNA. (Tr. Vol. I at 164:4-164:12; Falkinham Decl., at ¶ 12). Once the primer is bound to the DNA, DNA polymerase then initiates the primer extension process. (Falkinham Decl., at ¶ 12). Thus, when random primers are used, the resulting amplification process is referred to as "non-specific" because DNA synthesis begins at random locations anywhere on the target nucleic acid and any other nucleic acids that may be present in the samples. (Tr. Vol. I at 164:16-164:22; Tr. Vol. II at 237:7-238:2; Falkinham Decl., at ¶ 12). The use of those "non-specific" primers avoid the work required to select, make, and test specific primers for each individual target organism. (Falkinham Decl., at ¶ 12). TMA does not use non-specific primers or non-specific amplification. (Tr. Vol. I at 176:25-177:11; May 25, 2001 Statement of Facts, at Facts 27-28 [Docket #121]).
At the second step of TMA amplification, a reverse transcriptase enzyme recognizes the primer bound to the single-stranded viral RNA and extends the primer strand by synthesizing a new DNA strand complementary to the template viral RNA. (Tr. Vol. I at 177:7-177:16; Falkinham Decl., at ¶ 7). Reverse transcriptase ("RT") is a naturally occurring DNA polymerase enzyme that was first discovered in viruses. Life Techs., Inc. v. Clontech Lab., Inc., 224 F.3d 1320, 1322 (Fed. Cir. 2000) (discussing scientific facts about reverse transcriptase enzyme). RT's polymerase activity enables it to use either DNA or RNA molecules as a template to synthesize a complementary strand of DNA. Id. In addition to DNA polymerase activity, naturally-occurring RT also exhibits RNase H that degrades RNA while not affecting DNA molecules. Id. Gen-Probe's TMA process apparently uses such form of RT. (Tr. Vol. 1 at 179:8-179:10). As the enzyme progresses along the RNA template, the RT's RNase activity degrades the template viral RNA, leaving only the single-stranded DNA copy. (Tr. Vol. 1 at 178:23-1 79:10; Declaration of Scott Burwell in Support of Vysis' Opposition to Gen-Probe's Motion for Partial Summary Judgment of Noninfringement under the Doctrine of Equivalents ("First Burwell Decl."), at Exh. A, at 3-4).
At the third step, a second primer then binds to the single-stranded DNA copy. (Tr. Vol. I at 179:13-180:2; First Burwell Decl., at Exh. A, at 3-4). This second primer is designed to bind on the opposite side of the region to be amplified. (Tr. Vol. I at 179:13-179:15; First Burwell Del., Exh. A, at 4). RT then synthesizes a complementary strand of DNA based on that template, resulting in a double-stranded DNA molecule. (Tr. Vol. I at 179:25-180:7; First Burwell Decl., Exh. A, at 3-4).
The fourth step involves the transcription of new RNA strands by RNA polymerase enzymes based on the DNA strands generated in step two and three. (Tr. Vol. 180:10-181:17; First Burwell Decl., Exh. A, at 3-4). Although RNA polymerase does not necessitate a primer to initiate transcription, it requires a specific promoter sequence. (Tr. Vol. 180:19-181:2; Longiaru Decl., at ¶ 8). That promoter sequence is contained and generated when the primer binds to the target sequence in steps two and three. (Longiaru Deck, at ¶ 9). Thus, no transcription occurs unless RT has synthesized new DNA strands from the captured viral nucleic acid. If a promoter sequence was formed, RNA polymerase binds to it and initiate transcription of the DNA sequence, resulting in a transcribed RNA copy of the template DNA strand. (Tr. Vol. I at 180:23-181:17; First Burwell Decl., at Exh. A, at 3).
In the fifth step, one of the specific primers then binds to the newly transcribed RNA, and RT makes a new complementary DNA copy of that RNA strand. (Tr. Vol. 1 at 182:1-182:16; Longiaru Decl., at ¶ 10). The process of steps one through four repeats itself in a cyclic fashion, resulting in exponential amplification of only the particular target sequence of interest. (Tr. Vol. I at 181:18-181:25; Longiaru Decl., at ¶ 10). Since each of the DNA templates can make 100-1000 transcribed copies, this expansion can result in the production of 10 billion transcribed copies in less than one hour. (Tr. Vol. 1 at 182:19-182:23; First Burwell Decl., at Exh. A, at 3-4). The target sequence would then be present in sufficient amount for detection. (Tr. Vol. 1 at 183:11-184:16; First Burwell Decl., at Exh. A, at 5).
Gen-Probe has frequently compared its TMA technology to another well-known biotechnology technique called the polymerase chain reaction ("PCR"). (E.g., Tr. Vol. 144:10444:24; Falkinham Decl., at ¶ 11; Mullis Decl., at ¶ 21). As a type of "specific" amplification," PCR uses "specific" primers to select and amplify a chosen nucleic acid sequence a billionfold. (Falkinham Decl., at ¶ 11). In its traditional form, PCR results in exponential amplification of the target nucleic acid by producing an amount of DNA that doubles in each cycle of DNA synthesis. Genentech, Inc. v. Boebringer Mannheim GmbH, 47 F. Supp.2d 91, 99-100 (D. Mass. 1999) (providing a detailed discussion of PCR). First, the known target sequence is used to design two oligonucleotides to serve as specific primers, each one complementary to one of the two DNA strands and lying in opposite sides of the region to be amplified. Id., at 99. Those primers are then added to the reaction mixture containing the DNA to be amplified. The double-stranded DNA is then denatured by heating the mixture. Id. The first primer binds to its complementary sequence on the single strand. Id. DNA polymerase then initiates DNA synthesis starting with the primer and copies the sequence of the template strand, ultimately producing exact replicas of the target sequence. Id. After denaturation, the second, complementary primer then binds to the newly synthesized strand (at the opposite side of the region to be amplified) and provides the requisite starting point for DNA synthesis. Id. Although those two steps are described successively, they usually occur simultaneously using both strands of the template DNA as starting point. See id. The products of each duplication cycle then serves as a template for subsequent cycles, resulting in an exponential process of replication. Id. After repeated cycles of denaturation by heating and primer extension, the pool of DNA with the target sequence has been exponentially amplified, Id. Like PCR, TMA technology involves specific amplification, using specific primers, specific promoters, and specific polymerase enzymes. (Tr. Vol. VII at 1321:8-1321:19; May 25, 2001 Statement of Facts, at Fact 27 [Docket #121]).
IV. Substantive Pretrial Rulings
A few months after Gen-Probe initiated this action, Vysis voluntarily filed on March 8, 2000 an application with the PTO to reissue the `338 patent. Based on that application for reissue, Vysis moved for a stay of the litigation and for dismissal of the unfair competition claim. On May 10, 2000, the Court denied that motion. (May 10, 2002 Order Denying Motion to Stay Proceedings or to Dismiss Count 4 of the Amended Complaint [Docket #22]). The parties then proceeded with discovery.
On April 30, 2001, Gen-Probe filed a motion for partial summary judgment, arguing that the `338 patent describes and encompasses only methods of non-specific amplification and that its products do not incorporate non-specific amplification. On June 20, 2001, the Court issued an order granting Gen-Probe's motion for partial summary judgment of no literal infringement. (June 20, 2001 Order [Docket #144]). In that Order, the Court first construed the disputed term "amplifying." "Based on the explicit language of the specification, the repeated reference to non-specific amplification methods, and the absence of any reference to specific amplification or PCR, the Court construe[d] the term `amplifying' as found in the claims of the `338 patent to encompass only non-specific amplification." (Id. at 10). Because Vysis admitted that Gen-Probe's product uses specific amplification (Id., at 11), the Court ruled that Gen-Probe did not literally infringe the claims of the `338 patent.(Id.)
Vysis then sought entry of final judgment and a stay of the proceeding to permit it to appeal the June 10, 2001 summary adjudication. On July 19, 2001, the Court issued an order denying Vysis' motion for entry of final judgment and for a stay. (July 19, 2001 Order [Docket #158]).
After further discovery, Gen-Probe filed a motion for summary judgment of non-infringement, I contending that its assay did not infringe the `338 patent under the doctrine of equivalents. Vysis cross-moved for a reconsideration of the June 20, 2001 order, arguing that the claim limitation "amplify" encompassed specific amplification as well as non-specific amplification. On November 20, 2001, the Court issued an order addressing both motions. (Nov. 20, 2001 Order [Docket #200]). In that order, the Court first addressed Vysis' reconsideration request by comprehensively reviewing the controlling claim construction case law from the Federal Circuit and applying it to the intrinsic evidence related to the `338 patent. (Id., at 13-32). From that analysis, the Court reaffirmed its construction of the limitation "amplify" and denied Vysis' motion. (Id., at 31-32). Addressing Gen-Probe's motion, the Court ascertained that material issues of facts remained for the jury and denied the motion for summary judgment. (Id., at 33-38).
After the final pretrial conference on February 4, 2002 and more than two years after litigating this controversy, Vysis moved to dismiss the case for lack of subject matter jurisdiction on February 27, 2002. Having considered the parties' papers and arguments, the Court issued an order on March 12, 2002, denying the motion to dismiss. (Mar. 12, 2002 Order [Docket #334]). In that order, the Court ascertained that there was a reasonable apprehension of litigation to support an actual controversy and to vest the Court with subject matter jurisdiction over this declaratory action. (Id., at 9-16).
In addition to addressing the motion to dismiss and issuing its ruling on the parties' numerous motions in limine (Mar. 11, 2002 Order [Docket # 331]), the Court also granted the parties' request to file a few late summary adjudication motions to narrow issues for trial. On April 5, 2002, the Court issued its rulings on those motions. First, the Court determined as a matter of law that the effective filing date of the `338 patent pursuant to 35 U.S.C. § 120 was December 21, 1987. (Apr. 5, 2002 Order regarding Effective Filing Date [Docket #374]). Second, the Court construed additional claim limitations that the parties belatedly raised. (Apr. 5, 2002 Order Construing Claim Limitations [Docket # 375]). Third, the Court addressed the remaining motions in limine that were previously submitted. (Apr. 5, 2002 Order Denying without prejudice Vysis' Motion to exclude Allegedly Anticipatory Prior Art [Docket # 375]; Apr. 5, 2002 Order Granting in part and Denying in part Gen-Probe's Motion to Preclude Testimony and Evidence of Vysis' Intent to Abandon the `505 Application [Docket #376]).
About a week before trial and over two years after the initiation of the reissue proceedings, the PTO issued a notice of allowability on the reissue application but did not indicate when the patent would issue. The Court. however, exercised its discretion in declining to continue the trial or to further delay this case because the parties had ample notice of the trial date, there was no indication about when the PTO would complete its review of the pending reissue application and the reissue application had not yet issued as a patent. (Apr. 26, 2002 Order Regarding Request to Vacate Trial Date [Docket #381]). The parties then complied with the Civil Local Rules in preparation for trial.
V. The Trial
The trial in this case commenced on May 7, 2002. On May 22, 2002, the jury returned its special verdict, including an advisory verdict on issues of inequitable conduct and prosecution laches. (Special Verdict dated May 22, 2002 [Docket #446]). Pursuant to the jury's special verdict, the Court entered judgment on May 23, 2002 in favor of Gen-Probe on its declaratory action of non-infringement and invalidity based on obviousness and lack of enablement. (May 23, 2002 Judgment as to Infringement and Invalidity, as 2-3 [Docket #443]). The Court however submitted its ruling as to the equitable issues of inequitable conduct and prosecution laches. (Id., at 3). The parties subsequently filed the present motions for judgment as a matter of law.
LEGAL STANDARDS
I. Standards for Motions as a Matter of Law On Issues Triable by the Jury
Under Rule 50 of the Federal Rules of Civil Procedure, a court may grant a motion for judgment as a matter of law only where "there is no legally sufficient basis for a jury to find for [the non-moving] party." Fed.R.Civ.P. 50(a)(1). To prevail on a renewed motion for JMOL following a jury trial, the moving party "`must show that the jury's findings, presumed or express, are not supported by substantial evidence or, if they were, that the legal conclusions implied [by] the jury's verdict cannot in law be supported by those findings.'" Pannu v. Iolab Corp., 155 F.3d 1344, 1348 (Fed. Cir. 1998) (quoting Perkin-Elmer Corp. v. Computervision Corp., 732 F.2d 888, 893 (Fed. Cir.), cert. denied, 469 U.S. 857 (1984)). See also Applied Medical Resources Corp. v. U.S. Surgical Corp., 147 F.3d 1374, 1376 (Fed. Cir. 1998) (holding that the movant "must prove that the jury's factual findings were not supported by substantial evidence or that the facts were not sufficient to support the conclusions necessarily drawn by the jury on the way to its verdict.").
In order to determine whether a legally sufficient basis in fact exists, the Court must consider all the evidence and draw all reasonable inferences from the evidence in the light most favorable to the non-movant. Richardson-Vicks Inc. v. Upjohn Co., 122 F.3d 1476, 1479 (Fed. Cir. 1997); Perkin-Elmer Corp, 732 F.2d at 893 (Fed. Cir.), cert. denied, 469 U.S. 857 (1984). The Court may not determine the credibility of witnesses and must not "substitute its choice for that of the jury between conflicting elements of the evidence." Perkin-Elmer, 732 F.2d at 893. If, after this analysis, substantial evidence exists to support the jury's verdict, then the motion for JMOL must be denied. See Odetics, Inc. v. Storage Tech. Corp., 185 F.3d 1259, 1269 (Fed. Cir. 1999) (citations omitted).
Consequently, the court may grant JMOL in favor of a party bearing the burden of proof only where (1) the movant "has established [its] case by evidence that the jury would not be at liberty to disbelieve;" and (2) "the only reasonable conclusion is in [the movant's] favor." Nobelpharma AB v. Implant Innovations, Inc., 141 F.3d 1059, 1065 (Fed. Cir.), cert. denied, 525 U.S. 876 (1998) (citations omitted). See alao Omega Envt'l, Inc. v. Gilbarco, Inc., 127 F.3d 1157, 1161 (9th Cir. 1997) (stating that "judgment as a matter of law is appropriate when the evidence, construed in the light most favorable to the nonmoving party, permits only one reasonable conclusion, which is contrary to the jury's verdict."), cert. denied, 523 U.S. 812 (1998); Baker v. Delta Air Lines, Inc., 6 F.3d 632, 644 (9th Cir. 1993) (stating that the court "`must determine whether the evidence, considered as a whole and viewed in the light most favorable to the nonmoving party, reasonably can support only a verdict for the moving party'") (quoting Gillette v. Delmore, 979 F.2d 1342, 1346 (9th Cir. 1992)).
The essential question in deciding a motion for judgment as a matter of law is whether the evidence the jury could have believed in reaching its verdict was substantial enough to support its findings. Orthokinetics, Inc v. Safety Travel Chairs Inc., 806 F.2d 1565, 1573 (Fed. Cir. 1986). Thus, the question is not what the court might have believed, but what the jury could have reasonably determined. See Dawn Equip. Co. v. Kentucky Farms, Inc., 140 F.3d 1009, 1014 (Fed. Cir. 1998) ("[T]he inquiry is whether a reasonable jury, given the record before it viewed as a whole, could have arrived at the conclusion it did.").
II. Stahdards for Granting a New Trial
Under Federal Rule of Civil Procedure 59(a), "a new trial may be granted to all or any of the parties and on all or part of the issues in an action in which there has been a trial by jury, for any of the reasons for which new trials have heretofore been granted in actions at law in the courts of the United States." Fed.R.Civ.P. 59(a). The decision to grant or deny a new trial rests within the sound discretion of the court. Allied Chemical Corp. v. Daiflon, Inc., 449 U.S. 33, 36 (1980).
A trial court may grant a new trial if the verdict is "contrary to the clear weight of the evidence, or is based upon evidence which is false, or to prevent, in the sound discretion of the trial judge, a miscarriage of justice." Richardson v. Suzuki Motor Co., 868 F.2d 1226, 1245 (Fed. Cir.), cert. denied, 493 U.S. 853 (1989) (quoting Hanson v. Shell Oil Co., 541 F.2d 1352, 1359 (9th Cir. 1976), cert. denied, 429 U.S. 1074 (1977)). In general, a court should grant a new trial only when the judge "is left with the definite and firm conviction that a mistake has been committed." Landes Constr. Co. v. Royal Bank of Canada, 833 F.2d 1365, 1372 (9th Cir. 1987) (quoting 11 C. Wright A. Miller, Federal Practice and Procedure: Civil § 2806, at 49 (1973)). Thus, a jury verdict should ordinarily be set aside only when the verdict is against the weight of evidence or it is clear that the jury reached an erroneous result. Digidyne Corp. v. Data General Corp., 734 F.2d 1336, 1347 (9th Cir. 1984). It is true that, in making its determination, the court "can weigh the evidence and assess the credibility of witnesses, and need not view the evidence from the perspective most favorable to the prevailing party." Air-Sea Forwarders, Inc. v. Air Asia Co., Ltd., 880 F.2d 176, 190 (9th Cir. 1989). But, "a decent respect for the collective wisdom of the jury, and for the function entrusted to it in our system, certainly suggests that in most cases the judge should accept the findings of the jury, regardless of his own doubts in the matter." Landes Constr. Co, 833 F.2d at 1371 (quoting 11 C. Wright A. Miller, Federal Practice and Procedure: Civil § 2806, at 49 (1973)). It is insufficient that the district court would simply have reached a different verdict.Richardson, 868 F.2d at 1245.
III. Standards for Motions as a Matter of Law On Non-Jury Issues
Pursuant to the authority granted by Federal Rule of Civil Procedure 39(c), the Court submitted the equitable issues in this case to the jury for an advisory verdict. Fed.R.Civ.P. 39(c) ("In all actions not triable of right by a jury the court upon motion or of its own initiative may try any issue with an advisory jury . . . ."). The Court is, however, not bound by the advisory verdict. Rather, as required by Federal Rule of Civil Procedure 52(a), the Court must make independent findings of fact when trying a case with an advisory jury. Fed.R.Civ.P. 52(a) ("In all actions tried upon the facts without a jury or with an advisory jury, the court shall find the facts specially and state separately its conclusions of law thereon, and judgment shall be entered pursuant to Rule 58 . . . .").
Thus, "[w]hen, as here, trial is held before the district court with an advisory jury, the court must find the facts specially just as it would when conducting a bench trial without an advisory jury. Transmatic, Inc. v. Gulton Indus., 53 F.3d 1270, 1275 (Fed. Cir. 1995). "[F]indings of fact satisfy Rule 52(a) when they are sufficiently comprehensive and pertinent to the issue in dispute to form a basis for the district court's decision." Id, at 1276 (citing Atlantic Thermoplastics Co. v. Faytex Corp., 5 F.3d 1477, 1479 (Fed. Cir. 1993)). "Furthermore, although the district court need not make elaborate findings on every factual issue raised, it must find and specify as many subsidiary facts as necessary to inform the reviewing court of the steps by which it determined factual issues and reached its ultimate conclusions." Transmatic, 53 F.3d at 1276. As recognized by the Federal Circuit, those factual findings are entitled to substantial deference. Refac Int'l v. Lotus Dev. Corp., 81 F.3d 1576, 1582 (Fed. Cir. 1996). See also Anderson v. City of Bessemer, 470 U.S. 564 (1985) ("When findings are based on determinations regarding the credibility of witnesses, Rule 52(a) demands even greater deference to the trial court's findings; for only the trial judge can be aware of the variations in demeanor and tone of voice that bear so heavily on the listener's understanding of and belief in what is said."); First Interstate Bank of Billings v. United States, 61 F.3d 876, 882 (Fed. Cir. 1995).
DISCUSSION
1. Non-Infringement
In its special verdict, the jury determined that Vysis failed to prove by a preponderance of the evidence that, but for the license, Gen-Probe would have infringed the "338 patent under the doctrine of equivalents. (May 22, 2002 Special Verdict, at 1). In its post-trial motion, Vysis requests that the Court reconsiders the construction of the term "amplify" that formed the basis for the summary judgment of no-literal infringement and that the Court reverses the jury's verdict of non-infringement under the doctrine of equivalents. The Court declines to do so.
A. Legal Standards for Determining Infringement and for Construing Claims
Patent infringement analysis involves two steps. Gentry Gallery, Inc. v. Berkline Corp., 134 F.3d 1473, 1476 (Fed. Cir. 1998). "First, the claim must be properly construed to determine its scope and meaning. Second, the claim as properly construed must be compared to the accused device or process." Carroll Touch, Inc. v. Electro Mech. Sys., Inc., 15 F.3d 1573, 1576 (Fed Cir. 1993). See also Wang Laboratories, Inc v. America Online, Inc., 197 F.3d 1377, 1380 (Fed. Cir. 1999); EMI Group North America, Inc. v. Intel Corp., 157 F.3d 887, 891 (Fed Cir. 1998).
When construing the terms of a patent, the Court must first turn to "intrinsic evidence." Intrinsic evidence includes the claim itself, the specification, and the prosecution history of the patent. Vitrornics Corp. v. Conceptronic, Inc., 90 F.3d 1576, 1582 (Fed. Cir. 1996). Established rules of claim interpretation require that the Court first consider the words of the claims themselves, "both asserted and unasserted, to define the scope of the patented invention." Id. at 1582. The words are generally given their customary and ordinary meaning. Id. Hoechst Celanese Corp. v. BP Chemicals. Ltd., 78 F.3d 1575, 1578 (Fed. Cir. 1996) (stating that in defining technical terms, the Court should interpret it "as having the meaning it would be given by persons experienced in the field of the invention."). However, the Court must follow the definition of terms intended by the patentee if his or her special definition is clearly delineated in the specification or file history. Vitronics Corp., 90 F.3d at 1583; Hoechst Celanese Corp., 78 F.3d at 1578.
The Court also considers the specification to determine whether the inventor has employed any terms or words in a manner that is inconsistent with their plain and ordinary meaning. Vitronics, 90 F.3d at 1582. However, the claims, not the specification, define the invention so "not everything expressed in the specification must be read into all the claims." Sjolund v. Musland, 847 F.2d 1573, 1581-82 (Fed. Cir. 1988) (quoting Raytheon Co. v. Roper Corp., 724 F.2d 951, 957 (Fed. Cir. 1983)).
The Court also may review the prosecution history of the patent, if admitted into evidence. Vitronics, 90 F.3d at 1582. This history is "the complete record of all the proceedings before the Patent and Trademark Office, including any express representations made by the applicant regarding the scope of the claims" Id. It also includes prior art which is cited in the file history. Id. at 1583.
Although claim construction is a matter of law, Cybor Corp. v. FAS Techs., Inc., 138 F.3d 1448, 1456 (Fed. Cir. 1998) (en banc), the determination of infringement, whether literal or under the doctrine of equivalents, is a question of fact for the jury. Bai v. L L Wings, Inc., 160 F.3d 1350, 1353 (Fed. Cir. 1998). "In order for a court to find infringement, the plaintiff must show the presence of every . . . [limitation] or its substantial equivalent in the accused device."Wolverine World Wide, Inc. v. Nike Inc., 38 F.3d 1192, 1199 (Fed. Cir. 1994). Literal infringement requires the patentee to prove that the accused device contains each limitation of the asserted claim.Mas-Hamilton Group v. LaGard Inc., 156 F.3d 1206, 1211 (Fed. Cir. 1998). Infringement under the doctrine of equivalents requires the patentee to prove that the accused device contains an equivalent for each limitation not literally satisfied. Dawn Equip. Co. v. Kentucky Farms, 140 F.3d 1009, 1015 (Fed. Cir. 1998).
Under the doctrine of equivalents, "an element in the accused product is equivalent to a claim limitation if the differences between the two are `insubstantial' to one of ordinary skill in the art" DeMarini Sports, 239 F.3d at 1331-32. In appropriate cases, the function-way-result test offers additional guidance on the question of equivalence. Toro Co. v. White Consol. Indus., 266 F.3d 1367 (Fed. Cir. 2001) (citing Dawn Equip. Co. v. Kentucky Farms, 140 F.3d 1009, 1015 (Fed. Cit 1998)). Under that test, an accused device may infringe a claim under the doctrine of equivalents if it performs substantially the same overall function, in substantially the same way, to produce substantially the same overall result as the claimed invention. Graver Tank Mfg. Co. v. Linde Air Prods. Co., 339 U.S. 605, 608 (1950); Unidynamics Corp. v. Automatic Prod. Int'l, Ltd., 157 F.3d 1311, 1322 (Fed. Cir. 1998). The analysis of insubstantiality under this "function-way-result" test "should be applied as an objective inquiry on an element-by-element basis."Warner-Jenkinson, 520 U.S. at 40.
B. Claim Construction
Throughout this case, Vysis has repeatedly objected to this Court's construction of the limitation "amplify." In its June June 20, 2001, the Court explained the basis of its claim construction. (June 20, 2001 Order [Docket #144]). As it concluded after carefully applying Federal Circuit rules, "[b]ased on the explicit language of the specification, the repeated reference to non-specific amplification methods, and the absence of any reference to specific amplification or PCR, the Court construe[ed] the term `amplifying' as found in the claims of the `338 patent to encompass only non-specific amplification." (Id., at 10). In its November 20, 2001 order, the Court addressed Vysis' motion to reconsider that claim construction. (Nov. 20, 2001 Order [Docket #200]). Scrupulously applying the framework of claim construction precedent, the Court's order carefully and painstakingly analyzed and cited the overwhelming intrinsic evidence that supported the claim construction. (Id., at 13-32). From that analysis, the Court concluded that its original claim construction was correct. (Id., at 31-32). Both the June 20, 2001 Order and the November 20, 2001 Order are incorporated herein by reference. Consequently, the Court declines to reconsider and change its construction of the limitation "amplify."
The Court also declines to modify its construction of the other claim limitations as interpreted in its April 5, 2002 order. (Apr. 5, 2002 Order Construing Claim Limitations [Docket #375]). The Court also incorporates by reference the April 5, 2002 Order's extensive analysis. Consequently, the claim constructions remain unchanged.
C. Substantial Evidence Supports the Verdict of Non-Infringement by Equivalents
Vysis argues that it is entitled to judgment as a matter of law on the issue of infringement under the doctrine of equivalents. Having considered the entire record, the Court determines that there is substantial evidence to support the jury's verdict that, but for the license, Gen-Probe's accused products would not have infringed the `338 patent under the doctrine of equivalents.
The record indicates that the differences between the claims and the accused products, especially as to the amplification limitation, are not insubstantial. Indeed, Gen-Probe's TMA should amplify only a particular sequence of a target nucleic acid, not all of the nucleic acid present in the sample after target capture. (Tr. Vol. VII at 1313:9-1318:7).
An analysis under the function-way-result framework underscores this point. TMA functions differently from the patent by using specific primers designed to bind to a specific sequence in the target organism instead of the non-specific random hexamers disclosed in the patent. (Tr. Vol. VII at 1320:18-1321:7; Plaintiff's Exh. 105, internal Vysis letter from Dr. Richards dated Dec. 15, 1989 (stating that specific amplification methods `are the opposite of' non-specific random primer methods)). The way TMA amplifies the target polynucleotide after target capture also substantially differs from the claimed invention because TMA uses specific primers, specific promoters and specific polymerase enzymes while the patent amplifies through non-specific primers and enzymes. (Tr. Vol. VII at 1321:8-1321:19; Plaintiff's Exh. 105). Finally, TMA achieves a substantially different result from the use of random hexamers. (Tr. Vol. VII at 1321:20-1322:23). TMA increases the proportion of target sequences compared to other nucleic acid, i.e., increasing the number of needles in the haystack, as to permit detection of the target sequence. (Tr. Vol. VII at 1322:14-1322:23). The patent's non-specific method amplifies everything remaining after target capture, including whatever "junk" there may be left. (Id.). In other words, the patented method increases the number of needles by increasing the entire haystack and everything it contains. There was thus substantial evidence that the accused product functioned differently in a different way to achieve a different result.
Vysis attempts to overcome the non-infringement verdict by shifting the focus of the function-way-result inquiry and by presenting evidence contradicting Gen-Probe's. Vysis points to evidence that both specific and non-specific amplification perform the same function of making more copies of the target, in the same way by hybridizing primers to facilitate enzymatic synthesis, to achieve the same result of easing detection of the target polynucleotide. (Tr. Vol. VI at 1370:21-1373:1 and 1375:18-1377:6). Vysis also argues that Dr. Feinberg's testimony provides adequate evidence of infringement. (Tr. Vol. IV at 75 3:23-755:22). But, Vysis has already presented those arguments to the jury. And the jurors rejected that revisionist interpretation of the technology and Dr. Feinberg's testimony. Instead, the jury determined that the differences between the two methods of post-target capture amplification were substantial. (Tr. Vol. VII at 1320:18-1322:23).
In light of the entire record and the applicable legal standards, the Court determines that Vysis has not met its burden for a judgment as a matter of law of infringement under the doctrine of equivalents. See Perkin-Elmer, 732 F.2d at 893. Rather, Vysis is simply relitigating its case by presenting in its papers evidence that the jury has already considered and rejected. In doing so, it is asking the Court to substitute its views for those of the jury. In light of the controlling legal standards, the Court declines to do so. See Applied Medical Resources, 147 F.3d at 1376; Digidyne Corp, 734 F.2d at 1347. Therefore, the Court DEMES Vysis' motion for judgment as a matter of law on the issue of infringement by equivalents.
II. Invalidity Based on Obviousness and Lack of Enablement
In its special verdict, the jury determined that Gen-Probe proved by clear and convincing evidence that all the claims in the `338 patent were invalid as obvious under 35 U.S.C. § 103 and for lack of enablement under 35 U.S.C. § 112. (May 22, 2002 Special Verdict, at 2). Vysis now challenges the jury's verdict of invalidity and Gen-Probe opposes. Because substantial evidence and the controlling law support the jury's determination, the Court denies Vysis' motion for judgment as a matter of law of non-invalidity.
A. Legal Standards for Determining Invalidity
A party seeking to invalidate a patent must overcome a presumption that the patent is valid. 35 U.S.C. § 282; United States Gypsum Co. v. National Gypsum Co., 74 F.3d 1209, 1212 (Fed. Cir. 1996); Hybritech Inc. v. Monoclonal Antibodies, Inc., 802 F.2d 1367, 1375 (Fed. Cir. 1986). This presumption places the burden on the challenging party to prove the patent's invalidity by clear and convincing evidence. United States Gypsum Co., 74 F.3d at 1212.
The challenging party's burden also includes overcoming deference to the PTO's findings and decisions in prosecuting the patent application. Deference to the PTO is due "when no prior art other than that which was considered by the PTO examiner is relied on by the attacker." American Hoist Derrick Co. v. Sowa Sons, 725 F.2d 1350, 1359 (Fed. Cir.), cert. denied, 469 U.S. 821 (1984). Conversely, no such deference is due when the party challenging the patent raises prior art or evidence that was not considered by the PTO in its decision and evaluation of the patent application. Id. at 1360.
Unless a judgment as a matter of law is warranted, the Court must adopt the jury's finding that Gen-Probe has proved invalidity by clear and convincing evidence since the jury was not acting in its advisory capacity in rendering its verdict on validity. See Fed.R.Civ.P. 50(a);Beacon Theaters, Inc. v. Westover, 359 U.S. 500, 508-09 (1959); Dairy Queen, Inc. v. Wood, 369 U.S. 469, 479 (1962).
B. Obviousness
In challenging the jury's determination of obviousness, Vysis contends that Gen-Probe failed to provide any motivation to combine the prior art, that the closest prior art teaches away from the combination, that the objective indicia of non-obviousness favored its side, and that Gen-Probe argued an improper claim construction to the jury on closing. Those contentions are without merit.
1. Obviousness Legal Standards
Title 35 U.S.C. § 103 precludes the grant of a patent that is obvious to one of skill in the art.
That statute provides that:
if the differences between the subject matter sought to be patented and the prior art are such that the subject matter as a whole would have been obvious at the time the invention was made to a person having ordinary skill in the art to which said subject matter pertains.35 U.S.C. § 103. The ultimate determination of obviousness is a question of law based on underlying factual inquiries. Richardson-Vicks Inc. v. Upjohn Co., 122 F.3d 1476, 1479 (Fed. Cir. 1997); Specialty Composites v. Cabot Corp., 845 F.2d 981, 989 (Fed. Cir. 1988). Those factual inquiries involve consideration of the four Graham factors: (1) the scope and content of the prior art; (2) the differences between the claims and the prior art; (3) the level of ordinary skill in the pertinent art; and (4) any secondary considerations of nonobviousness, such as commercial success, long-felt but unresolved need, failure of others, copying, and unexpected results. See Graham v. John Deere Co. of Kansas City, 383 U.S. 1, 17-18 (1966); B.F Goodrich Co. v. Aircraft Braking Sys. Corp., 72 F.3d 1577, 1582 (Fed. (Dir. 1996); Miles Labs., Inc. v. Shandon. Inc., 997 F.2d 870, 877 (Fed. Cir. 1993).
The existence of each limitation of a claim in the prior art does not, by itself, demonstrate obviousness, because obviousness may not be established using hindsight. Kahn v. General Motors Corp., 135 F.3d 1472, 1479 (Fed. Cir. 1998). Instead, there must be a "reason, suggestion, or motivation in the prior art that would lead one of ordinary skill in the art to combine the references, and that would also suggest a reasonable likelihood of success." Smiths Indus. Med. Sys., Inc. v. Vital Signs, Inc., 183 F.3d 1347, 1353 (Fed. Cir. 1999). "Such a suggestion or motivation may come from the references themselves, from knowledge by those skilled in the art that certain references are of special interest in a field, or even from the nature of the problem to be solved." Id. at 1356. "Determining whether there is a suggestion or motivation to modify a prior art reference is one aspect of determining the scope and content of the prior art, a fact question subsidiary to the ultimate conclusion of obviousness." SIBIA Neurosciences, Inc. v. Cadus Pharm. Corp., 225 F.3d 1349, 1356 (Fed. Cir. 2000)
In determining obviousness, the invention must be considered as a whole and the claims must be considered in their entirety. Kahn, 135 F.3d at 1479-80. Because the jury returned a verdict in favor of Gen-Probe, the Court must presume that the jury resolved all factual disputes in its favor if substantial evidence supports the verdict. McGinley v. Franklin Sports, Inc., 262 F.3d 1339, 1351 (Fed. Cir. 2001); SIBIA Neurosciences, Inc. v. Cadus Pharm. Corp., 225 F.3d 1349, 1351 (Fed. Cir. 2000). However, Gen-Probe still bears the burden of showing invalidity as a result of obviousness by clear and convincing evidence. United States Surgical Corp. v. Ethicon, Inc., 103 F.3d 1554, 1564 (Fed. Cir. 1997).
2. First Graham Factor: Level of Skill in the Art
The testimony indicates that, generally, one of skill in this field would have a Ph.D. in the biological sciences. (Tr. Vol. IV at 669:16-669:17). Alternatively, the skilled artisan need not have a Ph.D. He would however have sufficient experience in working with molecular biology components. (Tr. Vol. IV at 669:10-669:21). Such experience would include many years of post-graduate studies and research in molecular biology, including work to isolate, characterize, clone, synthesize and amplify nucleic acids. (Tr. Vol. IV at 645:10-648:1 (Mark Berminger's experience); Id., at 667:12-669-5).
3. Second and Third Graham Factor: Scope and Content of the Prior Art and the Differences between the Prior Art and the Claimed Invention
The `338 patent teaches a combination of target capture and amplification of the isolated polynucleotide. It is that combination of known prior art that Vysis claims to be its invention. Thus, it does not dispute that the prior art separately discloses the target capture step and the amplification step. (Tr. Vol. I at 104:4-104:15 ("Amplification technology was known. Indeed, the raw materials to do target capture were known. The pieces were known and old.") It even admits it in its brief (Jun. 17, 2002 Vysis' Memorandum of Points Authorities in Support of its Motion for Judgment as a Matter of Law [Docket #448], at 2:3 (stating "Vysis admits that each step of its claimed process was disclosed in the prior art.")). The record contains substantial evidence of that fact.
Target capture of nucleic acids on a solid support was present in the prior art. As early as 1965, scientists had described the capture of nucleic acid molecules on a solid support. In a landmark publication, Dr. Gillespie and his colleagues immobilized denatured DNA on nitrocellulose membrane filters and then hybridized complementary RNA to the immobilized DNA. (Tr. Vol. III at 515:2-516:21; Plaintiff Exh. 40, Gillespie and Spiegelman, J. Mol. Biol. 12:829-842 (1965)). Prior art patents further teach the use of magnetic particles in nucleic acid hybridization. In their patent, Dr. Whitehead and his colleagues described the use of magnetic particles to isolate and separate enzymes and other proteins from a given medium. (Tr. Vol. II at 248:1-251:16; Plaintiff Exh. 85, U.S. Patent No. 4,554,088 (issued Nov. 19, 1985)). Similarly, Mr. Josephson's patent taught the application of magnetic particles in nucleic acid hybridization and isolation, specifically using complementary single-stranded nucleic acids attached to the magnetic particle to capture the target polynueleotides. (Tr. Vol. II at 253:6-257:3; Plaintiff Exh. 96, U.S. Patent 4,672,040 (issued Jun. 9, 1987) at cols. 10 and 17-18). A later patent issued to Mr. Stabinsky further discloses a method to isolate a target polynucleotide by using a "capture probe" partially attached to the solid support and partially complementary to the target nucleic acid. (Tr. Vol. III at 531:22-531:25; Plaintiff's Exh. 811, U.S. Patent No. 4,751,177 (issued Jun. 14, 1988) at col. 3). The Stabinsky patent also teaches the use of a "sandwich" technique in which a reporter probe is attached to the target polynucleotide. (Plaintiff's Exh. 811, at cols. 11-13). Accordingly, the prior art taught the use of target capture.
Although the Stabinsky patent issued after the effective date of the `338 patent, the reference is nonetheless prior art as of its filing date of June 13, 1985. 35 U.s.c § 102(e); Hazeltine Research v. Brenner, 382 U.S. 252, 254-55 (1965); Baxter Int'l, Inc. v. Cobe Lab., Inc., 88 F.3d 1054, 1062 (Fed. Cir. 1996).
Similarly, the prior art also taught amplification after target capture. For instance, Drs. Chu, Kramer and colleagues disclosed in their patent certain amplification methods after target capture. (Tr. Vol. III at 578:19-579-20; Id., at 584:10-584:23; Plaintiff's Exh. 146, U.S. Patent No. 4, 957, 858 (issued Sept. 18, 1990)). The Chu, Kramer patent disclosed amplification methods using Q replicase to make additional copies of the "reporter molecule" that was affixed to the detector probe hybridized to the target. (Tr. Vol. III at 583:19-584:23; Plaintiff's Exh. 146, at col. 3 ln. 51 to col. 4 ln. 42). The Chu, Kramer patent also disclosed the preparation of the target nucleic acid by capture on a solid support prior to amplification. (Plaintiff's Exh. 146, at col. 7, Ins. 7-60). Thus, as of December 21, 1987, Josephson disclosed the use of capture probes, Stabinksy taught the use of capture probes in a sandwich assay with a reporter probe, and Chu, Kramer disclosed amplification following target capture.
Although the face of the Chu, Kramer patent states that it was filed on April 16, 1988, that filing date is a typographical error. The PTO issued a certificate of correction that shows that the actual filing date is April 16, 1986. 28 As such, that patent constitutes prior art to the `338 patent. 35 U.S.C § 102(e); Brenner, 382 U.S. at 254-55;Baxter Int'l, 88 F.3d at 1062. The parties have stipulated to that fact, and the Court instructed the jury as to that stipulated fact.
Vysis concedes that the individual steps of its patents were in the prior art (Tr. Vol. I at 104:4-104:15; Vysis' Memorandum of Points Authorities in Support of Motion for Judgment as a Matter of Law [Docket #448] at 2:3), but argues that the combination of target capture and amplification is non-obvious. A skilled artisan in this narrow field, aware of all the prior art references, would however have received many explicit suggestions and had substantial motivation to combine those elements. "Such a suggestion or motivation may come from the references themselves, from knowledge by those skilled in the art that certain references are of special interest in a field, or even from the nature of the problem to be solved." Smiths Indus., 183 F.3d at 1356. In this case, there is substantial evidence that the suggestion to combine flowed from the nature of the problem, the knowledge of the skilled artisan and from the references.
The nature of the problem contained a motivation to combine. Those skilled in this field knew that every biologic assay had to include some specificity step. (Tr. Vol. II at 249:21C49:25V In this case, the well-known methods of non-specific amplification using random primers amplified any nucleic acid present in the sample. (E.g., `338 patent, Example 5 at col. 31 lns. 45-47). It was thus obvious to the skilled artisan to isolate or concentrate the target polynucleotide away from other nucleic acids in some manner before the non-specific amplification step. The specificity had to occur in the target capture step rather than the non-specific amplification step. Once the skilled artisan made that obvious and logical determination, he would focus on the target capture step, as taught in the Chu, Kramer patent, as the step with specificity. He could for example use nucleic acid sequences attached to magnetic beads solid support via ligands to capture a complementary nucleic acid of interest. (Tr. Vol. II at 250:1-250:11). Conversely, the use of a solid support to isolate and detect nucleic acids as described in the Josephson and Stabinsky references would militate for an amplification step. Indeed, the amount was often too small for detection, necessitating an amplification step. (Tr. Vol. II at 567:23-568:1). Hence, the problem to be solved in itself suggested the combination of the specific target capture followed by non-specific amplification.
Moreover, the knowledge of the skilled artisans would have also provided the suggestion to combine. For instance, the jury heard Dr. Walter King — one of the patent's inventor — admit that a skilled artisan at the time of the patent filing would have known how to combine target capture and amplification. (Tr. Vol. VIII at 1602:18-1602:20, videotape of Dr. King's Apr. 18, 2001 deposition at 181:2-181:20 played ("That at the time nonspecific amplification is much more feasible in the context of target capture. That to do target capture and specific amplification would have been very, very obvious or much, much easier to do . . . .")).
Even if the nature of the problem and the knowledge of the skilled artisan were insufficient, the prior art references would have supplied the requisite motivation to combine. Four references underscore this point. In the first reference, Brown described the isolation and separation of the target polynucleotides, and recognized the desirability of combining target capture on solid supports with an in vitro amplification. (Plaintiff's Exh. 169, Brown et al., "Methods in Gene Isolations," Ann. Rev. Biochem. 43:667-693 (1974); Tr. Vol. III at 567:12-569:1). Indeed, in their concluding remarks, the authors of the Brown reference recognized that "purification of important structural genes [using techniques described in the article] will have to be coupled with some method in which a small amount of a given gene can be increased enormously in amount[,]" such as "an amplification step [that] might be carried out in vitro by an efficient DNA polymerase, which would replicate faithfully each molecule of DNA many times." (Plaintiff's Exh. 169, at 687). The second reference by Arsenyan also suggests the combination of target capture followed by some form of amplification. (Plaintiff's Exh. 78, Arsenyan et al., "Isolation of Rat Liver 5S RNA Genes," Gene 11:97-108 (1980)). The Arsenyan scientific article taught the isolation and capture of a particular RNA through a cellulose column followed by amplification through cloning. (Tr. Vol. III at 576:11-577:1). The third reference, the Chu, Kramer patent, similarly taught the combination of target capture and amplification. (Tr. Vol. III at 579:6-579:20, 581:5-581:18, 582:10-583:1; Plaintiff's Exh. 146, col. 6-ln. 26 to col. 6-ln. 40, and col. 7-ln. 7 to col. 7-ln. 60). As the testimony at trial indicates, the Chu, Kramer patent represents an example of skilled artisans relying on the Brown article to combine target capture and amplification. (Tr. Vol. III at 581:19-582:9). The fourth reference, authored by Powell et al., similarly provides the requisite motivation to combine by describing the isolation of a poly(A) KNA through specific capture using oligo(dT) cellulose followed by PCR amplification. (Tr. Vol. 111 at 586:3-587:1; Plaintiff's Exh. 236, Powell et al., "A Novel Form of Tissue Specific RNA Processing Produces Apolipoprotein-B48 in the Intestine," Cell 50:831-840 (1987)).
Armed with the motivation from the above four references, a skilled artisan knowing the applicable prior art references in this narrow field would find it obvious to combine the Stabinsky and Josephson references to the Chu, Kramer patent. In re Dance, 160 F.3d 1339, 1343 (Fed. Cir. 1998) ("The teachings of the references, their relatedness to the field of the applicant's endeavor, and the knowledge of persons of ordinary skill in the field of the invention, are all relevant considerations. When the references are in the same field as that of the applicant's invention, knowledge thereof is presumed.") (citations omitted);Motorola, Inc. v. Interdigital Tech. Corp., 121 F.3d 1461, 1472 (Fed. Cir. 1997) ("[T]here is no requirement that the prior art contain an express suggestion to combine known elements to achieve the claimed invention. Rather, the suggestion to combine may come from the prior art, as filtered through the knowledge of one skilled in the art.").
Against this prima facie proof of obviousness, Vysis offers three weak rebuttal arguments. First, it counters that PCR made sample purification unnecessary and thus taught away from combining those prior art references. It is true that some scientists in the mid-1980's believed that the then-novel PCR technology could render unnecessary the purification of DNA before amplification. (Tr Vol. IV at 825:21-826:10 and 827:4-827:13; Defendant's Exh. D, K. Mullis et al., "Specific Enzymatic Amplification of DNA in Vitro: the Polymerase Chain Reaction" in Cold Spring Harbor Symposia on Quantitative Biology Vol. 51:263-273 (1986)). But, that was not a universal view held by most scientists at that time. (Tr. Vol. IV at 825:23-826:4). The combination was still possible and, once done, was hilly operational. In fact, as shown by the four references cited above, scientists at that time continued to believe that such combination was desirable. Therefore, PCR does not teach away from the invention as Vysis argues. See Tec Air, Inc. v. Denso Mfg Mich. Inc., 192 F.3d 1353, 1356 (Fed. Cir. 1999) ("A reference may be said to teach away when a person of ordinary skill, upon reading the reference, would be discouraged from following the path set out in the reference, or would be led in a direction divergent from the path that was taken by the applicant . . . [or] if it suggests that the line of development flowing from the reference's disclosure is unlikely to be productive of the result sought by the applicant.").
Second, Vysis argues that the Syvanen reference taught away from the combination that led to the invention by teaching amplification followed by a sandwich assay. (Tr. Vol. III at 621:11-622:8; Plaintiff's Exh. 79, Syvanen et al., Nucleic Acids Res. 12:5037-5048 (1986)). The Syvanen prior art only constitutes an instance of a plausible alternative combination of target capture and amplification. It does not teach away from the patent, because it neither discourages nor indicates as unproductive the capture of a target polynucleotide followed by amplification. See Tec Air, 192 F.3d at 1356.
Third, Vysis contends that there is no evidence that a skilled artisan would select specific target capture from among the other known purification methods to combine with amplification. (E.g., Tr. Vol. 11 at 412:2-412:14, 463:1-463:15, 417:4-417:24; Tr. Vol. 111 at 467:20-467:22 and 469:4-469:17; Plaintiff's Exh. 87, Daniel Kacian's notebook (using other purification methods)). Vysis' argument is erroneous legally and evidentiarily. The law of obviousness only requires that the elements of the patent were in the prior art and that there was a motivation to combine those elements. Ecolochem Inc. v. South. Cal. Edison, 227 F.3d 1361, 1371-72 (Fed. Cir. 2000). As discussed above, the record contains clear and convincing evidence that there were many suggestions to combine the target capture idea with a successive step of nucleic acid amplification. Nothing in the case law requires Gen-Probe to prove that target capture was the most preferred purification methods over other common' approaches. Moreover, the record indicates that people of skill in the art at that time would have selected target capture as a purification method to eliminate the effects of inhibitors on amplification techniques. (Tr. Vol. 1189:10-1192:10; 1200:10-1203:1).
In sum, Vysis' proffered evidence does not rebut the clear and convincing evidence of obviousness presented by Gen-Probe. The jury found obviousness after hearing the trial testimony and considering all the evidence, including the rebuttal evidence and arguments offered by Vysis, in light of Gen-Probe's evidence. In a judgment as a matter of law, the Court is not at liberty to substitute its own determination of the witnesses' credibility and assessment of conflicting evidence for those of the jury. See Perkin-Elmer, 732 F.2d at 893.
3. The Secondary Indicia of Obviousness
In addition to the Graham factors, the Federal Circuit requires that the district court considers secondary considerations of nonobviousness, such as commercial success, long-felt but unresolved need, failure of others, licensing, copying, and unexpected results. United States Surgical Corp. v. Ethicon, Inc., 103 F.3d 1554, 1563 (Fed. Cir. 1997). Vysis cites three of those factors — licensing, commercial success, and long-felt need — to rebut the compelling evidence of obviousness.
However, those three factors do not support Vysis' cause. For the objective evidence to be accorded substantial weight, its proponent must establish a nexus between the evidence and the merits of the claimed invention. SIBIA Neurosciences, 225 F.3d at 1358. "The term `nexus' is often used, in this context, to designate a legally and factually sufficient connection between the proven success and the patented invention, such that the objective evidence should be considered in the determination of nonobviousness." Demaco Corp. v. F. Von Langsdorff Licensing, Ltd., 851 F.2d 1387, 1392 (Fed. Cir. 1988). Although the patentee bears the burden of showing such nexus, SIBIA Neurosciences, 225 F.3d at 1358, Vysis did not present at trial any evidence showing a nexus between those factors and the patent. It has thus failed to satisfy its evidentiary burden.
Even if it had offered some evidence, Vysis would not have succeeded in supporting its claim of non-obviousness based on those objective factors. First, Vysis argues that the licenses taken by Gen-Probe, Bayer and Chiron indicates non-obviousness. (Tr. Vol. II at 391:11-391:17; Vol. III at 448:1-448:18). But, Vysis has not shown a nexus between the merits of the patent and those three licenses. In re GPAC Inc., 57 F.3d 1573, 1580 (Fed. Cir. 1995) ("Licenses taken under the patent in suit may constitute evidence of nonobviousness; however, only little weight can be attributed to such evidence if the patentee does not demonstrate a nexus between the merits of the invention and the licenses of record.") (internal quotations omitted). There is no proof that Vysis' competitors took a license to the `338 patent because they deemed the patent to be non-obvious and commercially successful. Rather, the record indicates that Gen-Probe entered into the license to settle pending litigations against Vysis' corporate parent and that Gen-Probe did not fully assess the merits of the patent when it took the license. (Tr. Vol. II at 366:10-371:24; Defendant's Exh. YH). Moreover, the other two licensees do not affect the analysis because, as Gen-Probe's alliance partners, Chiron and Bayer are not separate entities who have taken a license. (Tr. Vol. II at 391:6-391:14). Therefore, the existence of licenses without a showing that they relate to the merits of the invention does not support Vysis' claim of non-obviousness.
Second, Vysis argues that the patent was a commercial success, as shown by the $120 million in annual revenue that the blood screening product will generate for Gen-Probe. (Tr. Vol. I at 196:21-198:24). But, Vysis cannot rely on Gen-Probe's products to claim commercial success. As construed by the Court, the patent only encompasses non-specific amplification. (Jun. 20, 2001 Order [Docket #144], at 5-10; Nov. 11, 2001 Order [Docket #200], at 13-32). Differently from the patent and as undisputed by Vysis, Gen-Probe's product only involves specific amplification. (Jun. 20, 2001 Order, [Docket #144], at 11). Therefore, Vysis cannot meet its burden of showing that the commercially successful product is the actual invention disclosed and claimed in the `338 patent. See Demaco Corp., 851 F.2d at 1392. ("A prima facie case of thisnexus is generally made out when the patentee shows both that there is commercial success, and that the thing (product or method) that is commercially successful is the invention disclosed and claimed in the patent.") (internal quotations and citations omitted).
The Court's ruling that there was no literal infringement and the jury's determination of no infringement under the doctrine of equivalents buttress the point that Gen-Probe's commercial product is not the invention claimed in the "338 patent.
Third, Vysis contends that its invention satisfied a long-felt need for improving sample processing for nucleic acid amplification. To support that contention, Vysis points to Gen-Probe's admissions that target capture, combined with specific amplification in its commercial products, solved that need. (Tr. 197:15-198:24; Tr. 209:19-211:1; Plaintiff's Exh. 579-1; Defendant's Exh. PZ at 2-3). That contention, however, assumes that Gen-Probe's products correspond to Vysis' invention. As Gen-Probe's literature indicated, the combination of target capture and specific amplification in its Aptima Combo devices addressed the long-felt need of improving the amplification of nucleic acid. (Id.). There is no evidence that Vysis' patent, which combines target capture and non-specific amplification, resolved any such need. Without such evidence, Vysis has not supported its burden of showing a nexus between the secondary factors and the claimed invention. See Monarch Knitting Mach. Corp. v. Sulzer Morat GmbH, 139 F.3d 877. 884 (Fed. Cir. 1998).
Vysis has not satisfied its burden of providing evidence of a nexus between the objective indicia and the patent. Accordingly, the secondary factors do not support its claim of non-obviousness and its request to overturn the jury's verdict.
4. The Legal Conclusion of Obviousness
The ultimate determination of obviousness is a question of law based on underlying factual inquiries. Richardson-Vicks, 122 F.3d at 1479;Specialty Composites, 845 F.2d at 989. As discussed above, there is substantial evidence to support the jury's determination that the skilled artisan in this field had the motivation to combine the prior art reference of target capture and amplification. The secondary factors do not detract from that determination. See Newell Cos. v. Kenney Mfg. Co., 864 F.2d 757, 769 (Fed. Cir. 1988) (holding that because the record established such a strong case of obviousness based on the teachings of the prior art, the secondary factors do not by themselves overcome the conclusion of obviousness). Therefore, only one legal conclusion is possible based on those facts: the `338 patent is invalid for obviousness.
C. Enablement 1. Enablement Legal Standards
Title 35 U.S.C. § 112, paragraph 1 precludes the grant of a patent that lacks the enablement requirement. That statute provides that:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same. . . .35 U.S.C. § 112.
"The enablement requirement ensures that the public knowledge is enriched by the patent specification to a degree at least commensurate with the scope of the claims." Nat'l Recovery Techs. Inc. v. Magnetic Separation Sys. Inc., 166 F.3d 1190, 1195-96 (Fed. Cir. 1999). Accordingly, "[t]he scope of the claims must bear a reasonable correlation to the scope of enablement provided by the specification to persons of ordinary skill in the art" Genentech, Inc. v. Novo Nordisk A/S, 108 F.3d 1361, 1365 (Fed. Cir. 1997) (quoting In re Fisher, 427 F.2d 833, 839 (CCPA 1970)).
The scope of enablement in turn depends on the type of art at issue. "If an invention pertains to an art where the results are predictable, e.g. mechanical as opposed to chemical arts, a broad claim can be enabled by disclosure of a single embodiment." Spectra-Physics, Inc. v. Coherent, Inc., 827 F.2d 1524, 1533 (Fed. Cir. 1987). However, the scope of enablement is different for the unpredictable arts such as chemistry or biotechnology. "In unpredictable art areas, [the Federal Circuit] has refused to find broad generic claims enabled by specifications that demonstrate the enablement of only one or a few embodiments and do not demonstrate with reasonable specificity how to make and use other potential embodiments across the full scope of the claim." PPG Indus., Inc. v. Guardian Indus. Corp., 75 F.3d 1558, 1564 (Fed. Cir. 1996). See also In re Goodman, 11 F.3d 1046, 1050-52 (Fed. Cir. 1993); Amgen, 927 F.2d at 1212-14; In re Vaeck, 947 F.2d 488, 496 (Fed. Cir. 1991). As with other invalidity inquiries, "[e]nablement is determined from the viewpoint of persons of skill in the field of the invention at the time the patent application was filed." Ajinomoto Co. v. Archer-Daniels-Midland Co., 228 F.3d 1338, 1345 (Fed. Cir. 2000).
Once the full scope of enablement is determined, the enablement inquiry consists of determining whether the disclosure was sufficient to enable one skilled in the art to practice the full scope of the claimed invention without undue experimentation. Northern Telecom, Inc. v. Datapoint Corp., 908 F.2d 931, 941 (Fed. Cir. 1990). The Federal Circuit has held that a patent specification complies with the statute even if a "reasonable" amount of routine experimentation is required in order to practice a claimed invention, but that such experimentation must not be "undue." In re Wands, 858 F.2d 731, 736-37 (Fed. Cir. 1988) ("Enablement is not precluded by the necessity for some experimentation . . . . However, experimentation needed to practice the invention must not be undue experimentation. The key word is `undue,' not `experimentation.'") (footnotes, citations, and internal quotation marks omitted). In In re Wands, the court of appeals set forth a number of factors which a district court may consider in determining whether a disclosure would require undue experimentation:
(1) the quantity of experimentation necessary, (2) the amount of direction or guidance presented, (3) the presence or absence of working examples, (4) the nature of the invention, (5) the state of the prior art, (6) the relative skill of those in the art, (7) the predictability or unpredictability of the art, and (8) the breadth of the claims.Id. at 737. However, the district court need not review all of the factors when determining whether a disclosure is enabling. Amgen, Inc. v. Chugai Pharm. Co., Ltd., 927 F.2d 1200, (Fed. Cir. 1991) (noting that the Wands factors "are illustrative, not mandatory. What is relevant depends on the facts.").
Although enablement is a matter of law, that determination must be based on underlying factual inquiries. Enzo Biochem, Inc. v. Calgene, Inc., 188 F.3d 1362, 1369 (Fed. Cir. 1999). Judgment as a matter of law is therefore improper if substantial evidence supports the jury's factual findings. See Perkin-Eliner Corp. v. Computervision Corp., 732 F.2d 888, 893 (Fed. Cir. 1984).
2. Substantial Evidence Supports the Finding of Lack of Enablement
Vysis concedes that its invention is the combination of target capture and amplification. (Tr. Vol. 1 at 104:6-104:15). As such, the patent must enable one of ordinary skill in the art to make the invented combination, including each of its limitations. Presumably, Examples 4, 5, 6, and 7 in the written description should enable those amplification methods to the extent required by the law. ("338 patent, col. 30 ln. 14 to col. 32 ln. 25). The jury found that the patent lacked enablement. Having reviewed the record, the Court rules that the jury's verdict must stand because of the patent fails to adequately enable post-target capture amplification in this unpredictable field.
The parties have not implicated any other part of the written description as enabling those amplification following target capture.
Except for Examples 4 through 7, the `338 patent does not provide any specific teaching on the amplification step. Thus, the enablement analysis must focus on those examples. Upon scrutiny, the record shows that Examples 5, 6 and 7 are not enabled.
Indeed, the record indicates that Example 6 of the `338 patent fails to adequately enable the skilled artisan. Example 6 describes a method of non-specific enzymatic amplification using DNA polymerase enzymes primed by random hexamer primers. (`338 patent, col. 31 ln. 55 to col. 32 ln. 8). That example purports to teach exponential) non-specific amplification for producing approximately 1,000-fold increase in the level of target DNA. (Id. col. 32 ln. 4-5). But, the evidence at trial showed otherwise. The record suggests that none of the inventors did or could successfully practice the method of Example 6. (Tr. Vol. III at 532:1-532:19). Internal reports prepared by Gene-Trak, Vysis' corporate predecessor, further indicated the impracticability of that amplification method. (Plaintiff's Exh. 52, Monthly Report dated Sept. 21, 1987 (disclosing that amplification using random hexamer resulted in linear, rather than exponential, amplification and generated synthesis products of different length rather than one single target polynucleotide); Plaintiff's Exh. 56, Monthly Report dated Jan. 6, 1988 (acknowledging impracticability of random primers for amplification); Plaintiff's Exh. 57, Monthly Report Executive Summary dated Nov.-Dec. 1987 (stating that "[u]niversal, random primers appear to be of limited use for target amplification.")).
People with relevant skill in this field, like Mr. Berninger and Dr. Decker, also testified that Example 6 was not enabled. Mr. Berninger testified that the example fails to disclose any of the conditions necessary to achieve exponential amplification using random primers. (Tr. Vol. IV at 670:23-671:24). As Mr. Beminger told the jury, random priming amplification is very sensitive to changes in the protocol, requiring ample experimentation to achieve the desired result. (Tr. Vol. IV at 671:19-672:17). The quantity of experimentation that Mr. Berninger had to undertake is apparent from the extensive disclosures provided by the Hartley and Hartley/Berninger patents on amplification using random primers. (Plaintiff's Exh. 547, U.s. Patent No. 5, 043, 272 (issued Aug. 27, 1991); Plaintiff's Exh. 548, U.S. Patent. No. 5, 016, 727 (issued Apr. 21, 1992)). Dr. Scott Decker and his team at Gene-Trak were also unable to practice Example 6. (Tr. Vol. V at 873:17 and 873:25 where the videotape deposition of Dr. Decker taken on June 1, 2001 was played, including deposition testimony at 88:6-89:3, 95:3-97:14, 122:8-123:16, 129:4-130:2). Dr. Decker worked side-by-side with the patent's inventors at Gene-Trak and thus had access to the inventors' knowledge. The reports Dr. Decker prepared also indicated that he used methods and techniques more detailed than those disclosed in Example 6, but he was still unable to put it into practice. (Plaintiff's Exhs. 52 and 56). Although Vysis contends that neither Mr. Berninger nor Dr. Decker qualify as a skilled artisan in the art (E.g., Tr. Vol. VI at 1099:19-1100:5), the verdict suggests that the jury rejected Vysis' argument on this factual determination and found that those two researchers had the requisite ordinary skill in the field. Consequently, their work provides substantial evidence to support the jury's finding that Example 6 was not enabled.
Similarly, substantial evidence indicates that Example 7 of the `338 patent fails to enable. As the only other example that purports to teach exponential amplification, Example 7 describes exponential non-specific amplification using the RNA polymerase Q replicase enzyme. (`338 patent, col. 32 ln. 9-25). The record indicates that, with its conclusory sentences, Example 7 is impracticable even with undue experimentation. Dr. Kramer, recognized as one of the world's leading authorities on Q replicase, testified that the method described in Example 7 "would not work and did not work." (Tr. Vol. VI at 1208:11-1209:21 (Kramer's testimony); Tr. Vol. VIII at 1598:21-1598:22 (Dr. King testified that "Dr. Kramer is one of the world's experts on Q beta replicase enzyme."). Dr. Kramer further told the jury that the technology available in 1987 — or even today — could not achieve non-specific exponential amplification of RNA or DNA using Q replicase. (Tr. Vol. VI at 12 13:25-1214:10). Indeed, as Drs. Kacian and Kramer testified, Q replicase could not be used in non-specific amplification of different type of nucleic acids as promised by the patent. (Ir. Vol. VI at 1209:10-1209:2 1; Tr. Vol. II at 417:23-418:5). Because it is a highly specific enzyme "Q replicase would normally only copy Q viral RNA, nothing else," thereby sharply limiting its use. (Tr. Vol. II at 417:23-418:5). To buttress Drs. Kramer and Kacian's point, inventors Lawrie and King testified that they could not recall any efforts at Amoco — Vysis' former parent corporation — or at Gene-Trak to actually practice the method of Example 7. (Tr. Vol. III at 522:4-522:12 (Lawrie's testimony); Tr. Vol. VIII at 1598:2-1598:11 (King's testimony)). Moreover, the reference to the Blumenthal article in Example 7 does not provide an adequate disclosure sufficient to enable the claimed amplification of nucleic acids other than the Q polynucleotide itself (Tr. Vol. VI at 1210:14-1212:25). Rather, the Blumenthal reference only showed the initiation of Q 3 replicase-meditated synthesis; there was no evidence that Dr. Blumenthal even obtained a full copy of the desired polynucleotide. (Tr. Vol. VI at 1212:13-1212:25). Hence, that reference did not provide any teaching of the claimed use of Q replicase for exponential amplification of the target polynucleotide. Consequently, the record contains substantial evidence that Example 7 constituted an invitation to experiment, required unsuccessful and undue experimentation, and was simply not enabling.
Similarly, the record suggests that Example 5 in the `338 patent lacked teaching adequate to enable it. Example 5 describes a method of non-specific, linear amplification in which captured DNA templates are transcribed into RNA. (`338 patent, col. 31 ln. 24-54; Tr. Vol. III at 535:3-535:4). However, Dr. King, one of the inventors, testified that he is not aware of anyone ever making Example 5 work. (Tr. Vol. VIII at 1599:2-1599:7, 1600:9-1600:14). Dr. Lawrie, another one of the inventors, confirmed that, before he left Gene-Trak, he was not aware that anyone successfully implemented the teaching of Example 5. (Tr. Vol. III at 537:2-537:5). These admissions by the inventors are buttressed by the views of Dr. Kramer. (Tr. Vol. VI at 1275:4-1275:). Thus, there was substantial evidence in the record that Example 5 was also not enabled.
Dr. Kramer's testimony as to Example 5 occurred outside of the presence of the jury. Thus, his testimony on this point is not included in the Court's "substantial evidence" analysis. The Court merely cites Dr. Kramer's explanations on this point to buttress the substantial evidence provided by Drs. King and Lawrie's admission as to Example 5 and to illustrate what one skilled in the field would think.
Hence, the record indicates that there are substantial problems with the teachings of Examples 5, 6 and 7 in the `338 patent, and an analysis of the Wands factors indicates that undue experimentation is required to enable, if at all, the claimed invention. Indeed, two to three out of the four amplification examples in the patent are not practicable by one of skill in the art. As shown by the testimony related to those examples, there is evidence that one of skill in the art would have to perform extensive experimentation to practice the suggested amplification methods. The patent is simply an invitation to experiment the suggested amplification methods following target capture.
Indeed, such "invitation to experiment" falls short of teaching the full scope of the claimed invention in this unpredictable field of biological sciences. Because the biological art is considered unpredictable, the patent must provide a high degree of disclosure to avoid undue experimentation by the skilled artisan in the field. PPG Indus., 75 F.3d at 1564. Especially in the biological field, the Federal Circuit has admonished that "[t]o be enabling, the specification of a patent must teach those skilled in the art how to make and use the full scope of the claimed invention without `undue experimentation.'" Novo Nordisk A/S, 108 F.3d at 1365 (quoting In re Wright, 999 F.2d 1557, 1561 (Fed. Cir. 1993)). Indeed, "[t]he scope of the claims must be less than or equal to the scope of enablement." Nat'l Recovery Techs., 166 F.3d at 1196. The Federal Circuit has on many occasions invalidated biotechnology patent claims for lack of enablement where the narrow disclosure in the patent specification is not commensurate with the broad scope of the claims. E.g., In re Goodman, 11 F.3d 1046, 1050 (Fed. Cir. 1993) (invalidating patent claiming any mammalian peptide produced in plant cell based merely on example of producing gamma-interferon in tobacco plants); Amgen, Inc. v. Chugai Pharma. Co., 927 F.2d 1200, 1213-14 (Fed. Cir. 1991) (invalidating patent claiming all analogs of EPO protein based on only the EPO sequence and a few analogs); In re Vaeck, 947 F.2d 488, 495 (Fed. Cir. 1991) (invalidating patent claiming gene expression in all cyanobacteria despite only using one species of cyanobacteria in the examples).
This case presents another example of inadequate disclosure unable to support broad claims. The `338 patent's claims require non-specific amplification, including linear and exponential amplification. (`338 patent, col. 34 ln. 27 to col. 36 ln. 14). Yet, the specification fails to adequately teach such amplification. None of the preferred embodiments of exponential amplification following target capture is operative; neither Examples 6 nor 7 is practicable, if at all, without extensive experimentation. Even one of the two linear amplification preferred embodiments, Example 5, appears unworkable. As the disclosed preferred embodiments of the inventions, those examples necessary lie within the scope of the claimed invention. Vitronics Corp. v. Conceptronics, Inc., 90 F.3d 1576, 1582 (Fed. Cir. 1996); Modine Mfg. Co. v. United States Int'l Trade Comm'n, 75 F.3d 1545, 1550 (Fed. Cir. 1996). Their inoperativeness and impracticability leave substantial and unremedial "gaps" in the required scope of enablement. Despite claiming all forms of amplification following target capture, there is no enablement for exponential amplification and questionable enablement for linear amplification. To quote the Federal Circuit in an analogous case, "[t]his specification provides only a starting point, a direction for further research," not an enabling disclosure. Id.
In sum, there is substantial evidence to support the jury's finding that Examples 5, 6 and 7 in the `338 patent are neither operative nor practicable. Analyzing that finding in light of the Wands factors, it is clear that the limited scope of enablement falls short of the broad scope of the patented claims. Therefore, the `338 patent is invalid for lack of enablement.
3. Vysis' Attempt to Rebut the Lack of Enablement Fails
Vysis attempts to rebut the clear and convincing evidence by advancing six arguments. None of those contentions have merit.
First, Vysis contends that the jury's verdict of non-enablement conflicts with the verdict of obviousness. That contention has no merit. Obviousness under § 103 focuses on three major factual inquiries: (1) the level of skill in the art, (2) the disclosures and content of the prior art and (3) whether the "differences between the subject matter sought to be patented and the prior art are such that the subject matter as a whole would have been obvious. . . ." 35 U.S.C. § 103; Graham, 383 U.S. at 17-18; B.F. Goodrich Co., 72 F.3d at 1582. The inquiries for lack of enablement occur under a different legal standard. The enablement inquiry under § 112 focuses on the disclosure in the specification and on whether "the specification . . . contain(s) a written description of the invention, and of the manner and process of making and using it . . . to enable any person skilled in the art . . . to make and use the same . . . ." 35 U.S.C. § 112; Genentech, 108 F.3d at 1365. Given the differing standards and inquiries, it is possible for an invention to be obvious while its patent's specification fails to provide sufficient instruction to enable a skilled artisan to successfully make the invention to the full scope of the claims. Accordingly, Vysis' argument merely obfuscates the true issue at hand.
Second, Vysis argues that there was enablement as long as a person of ordinary skill in the art could have obtained, by any method whether disclosed in the patent or not, non-specific amplification of a target polynucleotide without undue experimentation. Based on that precept, Vysis cites to the testimony of Gen-Probe's witnesses as establishing Gen-Probe's failure to meet its burden of proof (Tr. Vol. IV at 845:16-845:22, 745:21-747:13, 786:17-787:10; Tr. Vol. VII at 1363:12-1363:22; Tr. Vol. I at 143:23-144:2; and Tr. Vol. III at 454:19-455:7). But, Vysis' argument fails because it relies on an erroneous legal standard. In patent law, it is clear that the scope of enablement of the specification varies inversely with the degree of unpredictability in the art. In re Angstadt, 537 F.2d 498, 502 (C.C.P.A. 1976) ("We note that many chemical processes, and catalytic processes particularly, are unpredictable and that the scope of enablement varies inversely with the degree of unpredictability involved.") (citations omitted). In a predictable art like the mechanical or electrical field, the degree of required enablement is low and the disclosure of a single embodiment would suffice. Spectra Physics, 827 F.2d at 1533. But, in an unpredictable field of art like molecular biology or biochemistry, the required scope of enablement is much greater. E.g., PPG Indus., 75 F.3d at 1564. As discussed above, the patent fails to teach the skilled artisan how to perform exponential amplification after target capture. Indeed, the only teaching as to exponential amplification appears in Examples 6 and 7, and neither of those examples adequately enable without undue experimentation. In this unpredictable art, it is insufficient to enable through only one operative embodiment. The patent has to enable to the full scope of the claimed invention, including exponential amplification. Nat'l Recovery Techs., 166 F.3d at 1196; Novo Nordisk A/S, 108 F.3d at 1365. The gaps in the disclosure of exponential amplification and linear amplification indicate a failure to enable to the full scope of the claimed invention in this unpredictable field. Vysis' argument must therefore fail.
Third, Vysis complains that Gen-Probe unnecessarily focused its case on the examples disclosed in the patent because a specification does not need to contain any example. See In re Marzocchi, 439 F.2d 220, 223 (C.C.P.A. 1971). Vysis ignores the fact that, except for Examples 4 through 7, the patent is devoid of enabling teachings on amplification. (See generally Plaintiff's Exh. 1, the `338 patent). The unpredictability of this field requires adequate teaching, not mere broad terminology and conclusory statements. If the jury and the Court did not look at the examples for evidence of amplification enablement, the patent would likely violate section 112.
Fourth, Vysis contends that Gen-Probe's evidence is refuted by Dr. Feinberg's testimony that a person of ordinary skill in the art could have achieved non-specific amplification using the method taught in Example 6. (See Tr. Vol. IV at 745:21-747:13 and 786:17-787:10). Vysis is asking the Court to rule as a matter of law that Dr. Feinberg's testimony has more weight and is more credible than Gen-Probe's witnesses and evidence. The Court declines to do so. It is the jury's function to weigh the evidence and determine credibility. Here, the jury had substantial evidence to reject Dr. Feinberg's testimony. Indeed, in his testimony, Dr. Feinberg continuously described Example 6 as a form of PCR. (Tr. Vol. IV at 745:21-747:13 and 786:17-787:10). The jury understood that, based on the Court's claim construction, the patent only encompasses non-specific amplification. The jury also heard evidence that POR was a specific form of amplification, different from the non-specific form disclosed in the patent. (E.g., Tr. Vol. III at 589:17-590:9). The jury could therefore determine that Dr. Feinberg's testimony held less credibility than the testimony of other witnesses. In a judgment as a matter of law, the Court is not at liberty to substitute its own determination of the witnesses' credibility and assessment of conflicting evidence for those of the jury. See Perkin-Elmer, 732 F.2d at 893. Dr. Feinberg's testimony is insufficient to overcome the jury's determination as to enablement.
Fifth, Vysis contends that Gen-Probe has not met its invalidity burden because Gen-Probe did not demonstrate that all of the examples were non-enabling. See Johns Hopkins Univ. v. CellPro, Inc., 152 F.3d 1342, 1361 (Fed. Cir. 1998). CellPro is distinguishable from this case. In affirming a summary judgment of enablement in CellPro, the Federal Circuit determined that an alternative embodiment, disclosed in the specification, sufficiently enabled the claimed invention despite the inoperativeness of the preferred embodiment. Id. In other words, the alternative embodiment sufficiently enabled the full scope of the claims. Here, even assuming that linear amplification were adequately enabled, the patent still fails to teach the skilled artisan how to perform exponential amplification after target capture without undue experimentation. Differently from CellPro, the "alternative" embodiment of linear amplification is insufficient to cover the full scope of the claimed amplification, since non-specific amplification encompasses both linear and exponential amplification. A gap in the enablement disclosure remains. And the Federal Circuit has invalidated many patents with such gaps. E.g., In re Goodman, 11 F.3d 1046, 1050 (Fed. Cir. 1993) (invalidating patent claiming any mammalian peptide produced in plant cell based merely on example of producing gamma-interferon in tobacco plants); Amgen, Inc. v. Chugai Pharma. Co., 927 F.2d 1200, 12 13-14 (Fed. Cir. 1991) (invalidating patent claiming all analogs of EPO protein based on only the EPO sequence and a few analogs); In re Vaeck, 947 F.2d 488, 495 (Fed. Cir. 1991) (invalidating patent claiming gene expression in all cyanobacteria despite only using one species of cyanobacteria in the examples).
Sixth, Vysis contends that the knowledge available in the art could supply the requisite enablement. See Atlas Powder Co. v. E.I. Du Pont de Nemours Co., 750 F.2d 1569, 1576-77 (Fed. Cir. 1984). That contention has no merit. In Atlas, the Federal Circuit explained that the claims at issue were not invalid, even if they covered inoperable as well as operable combinations of ingredients, because the skilled artisan would be able to use Bancroft's Rule, a basic principle of emulsion chemistry, to perform the claimed method. Id. at 1576. Here, there is no "basic principle" by which One can predict whether a disclosed non-specific amplification technique would work with any target polynucleotide. Not even the inventors were able to determine, as of the filing date, which technique could non-specifically amplify the target nucleic acid. In addition, there is substantial evidence that the knowledge in the public domain in 1987 was insufficient to substitute for this incomplete and inoperative disclosure. (E.g., Tr. Vol. VI at 1210:14-1212:25 and 1213:25-1214:10; Tr. Vol. V at 873:17 and 873:25; Tr. Vol. IV at 670:23-671:24). See Novo Nordisk A/S, 108 F.3d at 1366. Therefore, Vysis' last argument fails.
Consequently, Gen-Probe has provided clear and convincing evidence of a lack of enablement. Therefore, the Court concludes that the `338 patent is invalid for lack of enablement.
D. Summary of Invalidity Rulings
In sum, Gen-Probe has met its burden of showing by clear and convincing evidence that the patent-in-suit is invalid under 35 U.S.C. §§ 103 and 112. The substantial evidence presented at trial, when considered in light of the controlling law, requires a conclusion that the `338 patent is invalid as obvious and for lack of enablement. The Court consequently DENIES Vysis' motion for judgment as a matter of law that its patent is not invalid under §§ 103 and 112.
III. Inequitable Conduct
At trial and in its papers, Gen-Probe based its claim of inequitable conduct on three main grounds: Vysis has (1) failed to disclose to the PTO the "Chu/Kramer references," which consists of the Chu, Kramer patent and the manuscript by Lizardi et al.; (2) misrepresented the scope of the claimed invention as encompassing PCR; and (3) failed to disclose that it knew that Examples 6 and 7 were not enabled. The Court has reviewed the jury's advisory verdict on this issue, the evidence presented at trial, and the parties argument. For the following reasons, the Court holds that Gen-Probe failed to prove by clear and convincing evidence that inequitable conduct occurred in the prosecution of the `338 patent.
A. Legal Standards for Inequitable Conduct
To prove inequitable conduct in the prosecution of a patent, Gen-Probe must provide clear and convincing evidence of "affirmative misrepresentations of a material fact, failure to disclose material information, or submission of false material information, coupled with an intent to deceive." Baxter Int'l, Inc. v. McGaw, Inc., 149 F.3d 1321, 1327 (Fed. Cir. 1998) (citations omitted). To determine this issue, the district court must follow a two-step analysis: "first, a determination of whether the withheld reference meets a threshold level of materiality and intent to mislead, and second, a weighing of the materiality and intent in light of all the circumstances to determine whether the applicant's conduct is so culpable that the patent should be unenforceable." GFI, Inc. v. Franklin Corp., 265 F.3d 1268, 1273 (Fed. Cir. 2001).
In the first step, the district court must determine whether the withheld reference meets a threshold level of materiality and whether the evidence shows a threshold level of intent to mislead the PTO. Baxter, 149 F.3d at 1327. "Both intent and materiality are questions of fact reviewed for clear error." Id. "The more material the omission, the less culpable the intent required, and vice versa." Halliburton Co. v. Schlumberger Tech. Corp., 925 F.2d 1435, 1439 (Fed. Cir. 1991).
As to materiality, a reference, even if it is not prior art, is deemed material if there "is a `substantial likelihood that a reasonable examiner would consider it important in deciding whether to allow the application to issue as a patent.'" Halliburton, 925 F.2d at 1440 (quoting 37 C.F.R. § 1.56 (1989)). See also Akron Polymer Container Corp. v. Exxel Container, Inc., 148 F.3d 1380, 1382, (Fed. Cir. 1998). However, "a patentee need not cite an otherwise material reference to the PTO if that reference is merely cumulative or is less material than other references already before the examiner." Baxter, 149 F.3d at 1328. "When weighing whether uncited prior art is more material than that before the examiner, a trial court considers similarities and differences between prior art and the claims of the patent [and] must consider portions of prior art references which teach away from the claimed invention."Halliburton, 925 F.2d at 1440
Inequitable conduct also requires an intent to act inequitably. GFI, 265 F.3d at 1274. As the Federal Circuit recognized, "the facts in inequitable conduct cases rarely include direct evidence of admitted deceitful conduct." Id. (citing Molins PLC v. Textron, Inc., 48 F.3d 1172, 1180 (Fed. Cir. 1995)). Thus, "[t]he intent element of the offense is therefore in the main proven by inferences drawn from facts, with the collection of inferences permitting a confident judgment that deceit has occurred." Id. However, materiality of an undisclosed reference does not presume an intent to deceive. Allen Organ Co. v. Kimball Int'l, Inc., 839 F.2d 1556, 1567 (Fed. Cir. 1988). And, gross negligence does not of itself justify an inference of intent to deceive. Kingsdown Medical Consultants, Ltd. v. Hollister Inc., 863 F.2d 867, 876 (Fed. Cir. 1988). In a case involving an omission of a material reference to the PTO, there must be clear and convincing evidence that the applicant made a deliberate decision to withhold a known material reference. Molins, 48 F.3d at 1181. When examining intent to deceive, a court must weigh all the evidence, including evidence of good faith. Gambro Lundia AB v. Baxter Healthcare Corp., 110 F.3d 1573, 1580 (Fed. Cir. 1997).
Once the threshold levels of materiality and intent have been established, the trial court must weigh materiality and intent. Molins, 48 F.3d at 1178. The more material the omission, the less evidence of intent will be required in order to find that inequitable conduct has occurred. N.V. Akzo v. E.I. du Pont de Nemours Co., 810 F.2d 1148, 1153 (Fed. Cir. 1987). In light of all the circumstances, the court must then determine whether the applicant's conduct is so culpable that the patent should be held unenforceable. LaBounty Mfg., Inc. v. United States Int'l Trade Comm'n, 958 F.2d 1066, 1070 (Fed. Cir. 1992). The district court's ultimate determination of inequitable conduct is reviewed under an abuse of discretion standard. Kolmes v. World Fibers Corp., 107 F.3d 1534, 1541 (Fed. Cir. 1997).
B. There Is No Inequitable Conduct Based on the "Chu/Kramer References"
At trial, Gen-Probe argues that Vysis intentionally and fraudulently withheld two allegedly material prior art references from the PTO: (1) U.S. Patent No. 4,957,858 (issued Sept.18, 1990) invented by Chu, Kramer et al. (Plaintiff's Exh. 146), and (2) the related manuscript by Lizardi et al., "Billion-fold amplification of recombinant-RNA hybridization probes," dated December 1987. (Plaintiff's Exh. 235). Vysis concedes that the inventors and Vysis' patent counsel did not disclose those references to the PTO. (Tr. Vol. V at 977:4977:6). The Court must therefore decide whether the references are material, whether the failure to disclose is evidence of an intent to deceive, and in light of those findings whether Vysis committed inequitable conduct.
1. The Jury's Obviousness Verdict Does Not Affect This Equitable Inquiry
At the threshold of the inquiry, Gen-Probe contends that the jury's verdict on obviousness is binding on the Court in its disposition of any accompanying equitable claim. See Cabinet Vision v. Cabnetware, 129 F.3d 595, 600 (Fed. Cir. 1997). Specifically, Gen-Probe argues that, by determining that the `338 patent was obvious, the jury found that the Chu/Kramer prior art was material evidence for inequitable conduct. It further cites two Federal Circuit cases that it claims to be applicable to this case: Semiconductor Energy Lab. Co. v. Samsung Elecs. Co., 204 F.3d 1368, 1374 (Fed. Cir. 2000); BF Goodrich Co. v. Aircraft Braking Systems Corp., 72 F.3d 1577, 1584 (Fed. Cir. 1996). The argument has no merit.
First, the cases from the Federal Circuit that Gen-Probe cites to support its argument are inapplicable here. BF Goodrich andSemiconductor involved bench trials in which judges made explicit factual findings that the undisclosed references rendered the claimed invention obvious. In other words, those cases did not implicate jury findings. Thus, neither case involved the Seventh Amendment's imperative to preserve the jury's function as a fact-finder and to defer to the jury's findings on related equitable issues. Moreover, in BF Goodrich, the district court's holding of obviousness in that case was not the basis for the Federal Circuit's determination of materiality in the inequitable conduct inquiry. BF Goodrich, 272 F.3d at 1584. Therefore, Gen-Probe has no legal basis to support its contention.
Second, there is no clear factual basis to support Gen-Probe's contention. Although the jury found the patent-in-suit obvious, the jurors did not make any express and specific factual finding that the Chu/Kramer patent or the Lizardi manuscript were material evidence that formed the basis of their determination. It is likely that those references were material to the jury's obviousness determination. But, the special verdict form does not indicate which prior art the jury relied upon. Given the ambiguity of the special verdict as to the prior art upon which the jury relied, the Court declines to rule conclusively that the jury found the Chu/Kramer references to be material.
However, as discussed above, it is clear that Gen-Probe provided clear and convincing evidence to support its claim under section 103, and that substantial evidence supported the jury's determination of obviousness.
2. Materiality of the Chu/Kramer References
Vysis does not dispute that the prior art separately discloses the target capture step and the amplification step because it concedes that its invention is the combination of those two steps (Tr. Vol. I at 104:4-104:15). Although arguably not anticipatory, the Chu/Kramer references appears to refute, or at least show inconsistencies in, the patentability position that Vysis adopted.As discussed above, the Chu, Kramer patent disclosed certain amplification methods following target capture. See Discussion, Part II.B., supra, at 24 (citing Tr. Vol. III at 578: 19-579-20 and at 584:10-584:23; Plaintiff's Exh. 146). Specifically, the Chu, Kramer patent disclosed amplification methods using Q replicase to make additional copies of the "reporter molecule" affixed to the detector probe hybridized to the target. (Tr. Vol. III at 583:19-584:23; Plaintiff's Exh. 146, at col. 3 ln. 51 to col. 4 ln. 42). The Chu, Kramer patent also disclosed the preparation of the target nucleic acid by capture on a solid support prior to amplification. (Tr. Vol. III at 581:5-583:1; Plaintiff's Exh. 146, at col. 7, Ins. 7-60). The Chu, Kramer patent thus appears to contradict Vysis' position that the prior art did not teach the combination of the target capture followed by amplification.
During the reissue proceeding, the PTO specifically considered the Chu, Kramer patent and the related argument offered by Gen-Probe in examining the same claims as in the `338 patent. (Tr. Vol. V at 995:8-995:15 and 996:25-997:3). However, the examiner did not reject the reissue patent over the Chu, Kramer patent. (Tr. Vol. V at 998:25-999:7). The examiner's reissue determination is probative evidence rebutting Gen-Probe's contention of materiality. J.P. Stevens Co. v. Lex Tex Ltd., 747 F.2d 1553, 1562 (Fed. Cir. 1984) (holding that the result of a PTO proceeding that assesses patentability in light of information not originally disclosed can be of strong probative value in determining whether the undisclosed information was material). Although what the particular examiner did on reissue in this case is not conclusive of the materiality inquiry, Molins, 48 F.3d at 1179-80, it remains probative evidence of what the hypothetical "reasonable examiner" would do.
In light of the totality of the evidence on this issue, Gen-Probe has not met its burden. Although the Chu/Kramer references provide a strong basis for a determination of obviousness, the materiality inquiry looks beyond that and attempts to determine what a reasonable examiner would do in such situation. The legal standards are thus different. Applying the proper standard to the evidence provided by Gen-Probe and Vysis on this issue, the Court is not convinced by clear and convincing evidence that a reasonable examiner would have substantially found those references to be important to his determination of patentability. Thus, the Court finds that Gen-Probe has not shown by clear and convincing evidence that the reasonable examiner would have determined the references to be material.EMC, 835 F.2d at 1415.
2. No Intent to Deceive Regarding Chu/Kramer References
At trial, Gen-Probe based its intent to deceive argument on certain interactions between Dr. Kramer and Gene-Trak. On June 19, 1987, Gene-Trak invited Dr. Kramer to make a presentation to its scientists. (Tr. Vol. VI at 1192:11-1193:2). Dr. Lawrie, among other Gene-Trak personnel, attended that presentation. (Tr. Vol. VI at 1193:16-1194:5). In the course of that presentation, Dr. Kramer shared with Gene-Trak personnel the ideas ultimately contained in the Chu, Kramer patent. (Tr. Vol. VI at 1194:6-1195:8). Gene-Trak became very interested in Dr. Kramer's work and decided to take a license to his patent. (Tr. Vol. VI at 1195:9-1197:17; Plaintiff's Exh 143, letter from Gene-Trak to Dr. Kramer regarding his well-received presentation). In addition to Dr. Lawrie, Mr. Galloway also knew Dr. Kramer, who was a member of Vysis' scientific advisory board, and knew that Vysis had licensed the Chu, Kramer patent. (Tr. Vol. V at 976:9-977:6). In essence, Gen-Probe has shown evidence that Dr. Kramer made a well-received presentation to Gene-Trak in 1987 and that Gene-Trak subsequently licensed Dr. Kramer's technology.
Gen-Probe then attempts to fit those facts into the scenario of GFI, Inc. v. Franklin Corp., 265 F.3d 1268, 1274-75 (Fed. Cir. 2001). But,GFI is distinguishable. In that case, the Federal Circuit found the requisite intent to deceive because, despite knowing about the prior licensing discussion and the fact that prior art covered its patent, the patentee in the GFI affirmatively distinguished its invention from those prior art references in its response to the PTO. Id. Thus, the patentee in GFI affirmatively misled the PTO regarding the material prior art references. Here, Gen-Probe has not provided any similar evidence of deliberate intent to deceive. The Court thus finds that Gen-Probe has not met its burden as to the intent prong. Therefore, the Court concludes that Vysis did not commit inequitable conduct in failing to disclose the Chu/Kramer prior art.
C. There Is No Inequitable Conduct Based on the PCR Disclosures
At trial, Gen-Probe further claimed that Vysis intentionally misrepresented the intended scope of the claimed invention as encompassing PCR. Gen-Probe, however, failed to provide the required clear and convincing evidence to satisfy its burden on the issues of materiality and intent.
1. The Materiality of the PCR Disclosures
Evidence is "material" if there is a "substantial likelihood that a reasonable examiner would consider it important in deciding whether to allow the application to issue as a patent.'" Halliburton, 925 F.2d at 1440. The reasonable examiner would consider something important if it "refutes, or is inconsistent with a position the applicant takes in . . . [a]sserting an argument of patentability." 37 C.F.R. § 1.56. As part of its inequitable conduct claim, Gen-Probe argues that Vysis belatedly claimed that its invention encompassed PCR but failed to disclose the inventors' contradictory statements and drawings.
Indeed, the PTO initially rejected the application in light of many references, including the PCR article authored by Dr. Mullis. (Defendant's Exh. OV at 245-246; Defendant's Exh. OW at 359-360). Instead of properly replying to that rejection, the applicants abandoned the application and filed a continuation, and repeated that process multiple times. (Apr. 5, 2002 Order Granting Vysis' Motion for a Determination That Effective Filing Date of `338 Patent Is 12/21/87 [Docket #374], at 4-8 (Providing an overview of the complicated prosecution history)). Some eight years after the applicants filed the first application, Vysis finally responded to the merits of the PTO's rejections and belatedly asserted that its technique encompassed PCR. On December 5, 1995, the inventors submitted a' preliminary amendment (Plaintiff's Exh. 3 at VI 31662-361681), in which they suggested that the invention represented an improvement to the PCR amplification methods. (Id., at VI 31672-31673). To reinforce that suggestion, Dr. David Persing submitted a declaration to the PTO on July 9, 1997, arguing that those skilled in the art did not recognize the potential effect of inhibitors on the operation of the PCR specific amplification method until after the filing of the patent application. (Id., at VI 31493-31500). Based on that preliminary amendment and Dr. Persing's argument, the PTO withdrew its prior objections and allowed the claims to issue as a patent. (Id., at VI 31547-31548).
The record suggests that Vysis failed to disclose to the PTO certain information that appears inconsistent with its position that its patent encompasses PCR. It did not tell the PTO that the inventors held views that contradicted Vysis' position. For instance, Dr. Lawrie acknowledged that the patent disclosed amplification methods "other than PCR." (Tr. Vol. III at 525:19-526:9). Similarly, Dr. King's testimony indicates that the inventors were looking for a method different from PCR. (Tr. Vol. VIII at 1595:5-1595:9, where the videotape deposition of Dr. King taken on April 18, 2001 was played, including deposition testimony at 45:3-45:24 (stating in part "Vysis did not have an amplification method, a licensed amplification method. So we felt that it was important that we either seek one out or invent one or have, you know, the ability to demonstrate that we have an amplification method that was different than PCR.")).
To overcome this evidence, Dr. King and Dr. Lawrie testified that the patent-in-suit could encompass PCR technology. Dr. King's testimony intimated that his patent's broadest claims and specification did not exclude specific amplification techniques. (Tr. Vol. VIII at 1570:16-1571:24 and 1572:5-1579:8). On the stand, Dr. King further stated that his invention contemplated any amplification method, including PCR. (Tr. Vol. VIII at 1581:5-1581:11). Similarly, Dr. Lawrie told the jury that the claims did not exclude the use of non-specific amplification (Tr. Vol. III at 541:8-541:11) or exclude specific enzymes or primers. (Tr. Vol. III at 541:12-542:15).
Having heard the testimony and scrutinized the witnesses' demeanor on the stand, the Court concludes that the inventors' testimony was not filly credible. It is thus unclear which part of their testimony was actually reliable. In the same testimony, Dr. Lawrie affirmed that his invention encompassed PCR while being different from PCR. (Compare Tr. Vol. III at 541:8-542:15 and Tr. Vol. III at 525:19-526:9). Similarly, Dr. King's trial testimony and his previous deposition under oath are contradictory on the inclusion of PCR within the claims' scope. (Compare Tr. Vol. VIII at 1595:5-1595:9 and Tr. Vol. VIII at 1581:5-1581:11). The witnesses were either confused or self-serving. Either way, their testimony is unreliable on this issue.
Moreover, Drs. King and Lawrie's testimony is not reliable because it contradicts the intrinsic patent evidence. As the Federal Circuit recognized, "the subjective intent of the inventor when he used a particular term is of little or no probative weight in determining the scope of a claim (except as documented in the prosecution history)."Markman v. Westview Instruments, Inc., 52 F.3d 967, 985 (Fed. Cir. 1995) (en banc), aff'd, 517 U.S. 370 (1996). See also Bell Howell Document Management v. Altek Sys., 132 F.3d 701, 706 (Fed. Cir. 1997) ("The testimony of an inventor and his attorney concerning claim construction is thus entitled to little or no consideration. The testimony of an inventor is often a self-serving, after-the-fact attempt to state what should have been part of his or her patent application . . . ."); Roton Barrier, Inc. v. Stanley Works, 79 F.3d 1112, 1126 (Fed. Cir. 1996) ("We have previously stated that an inventor's after-the-fact testimony is of little weight compared to the clear import of the patent disclosure itself") (internal quotation marks omitted). The Court has already carefully and comprehensively reviewed the specification and the prosecution history. (Nov. 20, 2001 Order [Docket #200] at 21-31). From that analysis of the intrinsic evidence, the Court determined that the `338 patent does not encompass specific amplification. (Id., at 32). Since the inventors' statements regarding PCR are unreliable, the Court declines to find them material because a reasonable examiner would not reasonably consider them in his decision.
As a second basis for a finding of materiality, Gen-Probe submits drawings created by Dr. Lawrie in the late 1980's. (Plaintiff's Exh. 42 at VI 129773; Plaintiff's Exh. 43 at VI 129781). Those drawings cautioned that the invention was "too close to Cetus," the assignee to the PCR patent. (Id.). Vysis did not submit those drawings to the PTO during the prosecution of the `338 patent. (Tr. Vol. V at 974:8-974:19 and 975:18-976:1).
The drawings are, however, irrelevant to patentability. They only relate to whether the practice of the depicted process using specific amplification would infringe the Cetus patents. The reasonable examiner would not find such information material since overlapping patent rights do not affect the PTO's patentability inquiry. Atlas Powder Co., 750 F.2d at 1580-81 (noting that the "well-known fact that a very considerable portion of the patents granted are in a field covered by a former relatively generic or basic patent, are tributary to such earlier patent, and cannot be practiced unless by license thereunder.") (quotingHerman v. Youngstown Car Mfg. Co., 191 F. 579, 584-85 (6th Cir. 1911)).
Moreover, the reissue proceeding supports the idea that the drawings are not material. During the reissue proceeding, those drawings and notes were submitted to the PTO as part of Gen-Probe's motion for summary judgment of no literal infringement. The PTO did not rely on those drawings to make its rejection, providing probative evidence of non materiality. J.P. Stevens Co. v. Lex Tex Ltd., 747 F.2d 1553, 1562 (Fed. Cir. 1984).
In sum, the reasonable examiner would not have relied on either the inventors' statements or their drawings in his patentability determination. Therefore, the Court finds the Gen-Probe failed to satisfy its burden as to the threshold issue of materiality related to the POR disclosures.
2. The Lack of Intent Regarding The PCR Disclosures
In a case involving an omission of a material reference to the PTO, there must be clear and convincing evidence that the applicant made a deliberate decision to withhold a known material reference. Molins, 48 F.3d at 1181. Here, the Court finds that Gen-Probe did not provide clear and convincing evidence of an intent to deceive the PTO regarding the PCR disclosures.
To satisfy its burden, Gen-Probe points to the preliminary amendments in 1995 as proof of the intent to deceive. The Court sees no deceit in such evidence. December 1995 was the first time that Vysis responded to the merits of the PTO's rejections. Between 1987 and 1995, Vysis repeatedly abandoned its application when faced with the same rejection from the PTO and then filed a new continuation application. (Apr. 5, 2002 Order Granting Vysis' Motion for a Determination That Effective Filing Date of `338 Patent Is 12/21/87 [Docket #374], at 4-8). Nevertheless, the law requires evidence — actual or circumstantial — of a deliberate decision to withhold the material information. Molins, 48 F.3d at 1181. Having presided over this trial, the Court finds that there is insufficient evidence that Vysis, its attorneys and the inventors intended to deceive the PTO.
Gen-Probe cannot buttress its argument based on a supposed "duty to investigate" imposed on Mr. Galloway, the patent attorney who prosecuted the `338 patent. There is no authority that imposes on a patent attorney such a duty to investigate under similar circumstances. In the only case that Gen-Probe cited for that proposition, Brasseler, U.S.A. I., L.P. v. Strker Sales Corp., 267 F.3d 1370, 1380 (Fed. Cir. 2001), the Federal Circuit did not create such "duty to investigate" or impose any similar obligation. The Court declines to carve out a new duty that is unsupported by precedent or statute. In any case, the Court had the opportunity to hear Mr. Galloway's testimony and observe his demeanor during trial. Based on that scrutiny, the Court finds that Mr. Galloway's testimony regarding his lack of intend to deceive the PTO on this issue is credible. Therefore, the Court concludes that Vysis did not intend to deceive the PTO regarding the PCR disclosures.
In sum, Gen-Probe has failed to provide clear and convincing evidence that Vysis deliberately withheld from the PTO the material information regarding the scope of the claims vis-a-vis PCR. Since there was no materiality and no intent to deceive, the Court concludes that Gen-Probe has not met the threshold of the inequitable conduct inquiry and that its attack based on this issue fails.
D. There Is No Inequitable Conduct Based on Failure to Enable Examples 6 7
Gen-Probe further contends that Vysis intentionally withheld from the PTO the fact that Examples 6 and 7 were inoperative and not enabled. Having considered the evidence, the Court determines that Gen-Probe has not proved by clear and convincing evidence that there was an intent to deceive the PTO regarding the inoperativeness of Examples 6 and 7.
As extensively discussed in this order's invalidity section, there was substantial evidence to support the jury's verdict that the patent fails to fully enable the skilled artisan to make the invention. See Discussion, Part II.C.2-3, supra, at 32-40. Indeed, there is strong evidence that neither Examples 6 or 7 of the `338 patent provides sufficient enabling disclosure. Id., Part II.C.2, supra, at 32-37. And, the record also suggests that Vysis did not submit that information to the PTO. For instance, it never submitted Dr. Decker's reports or findings regarding the inoperability of Example 6. (Tr. Vol. V at 976:2-976:8). A reasonable patent examiner would likely consider such information important in deciding whether to allow the issuance of the patent, because the information affects the patentability requirement under § 112 and appears inconsistent with certain patentability positions taken by Vysis during the prosecution of the `338 patent.Halliburton, 925 F.2d at 1440. That information appears to be material.See LaBounty Mfg., Inc. v. United States Int'l Trade Comm'n, 958 F.2d 1066, 1076 (Fed. Cir. 1992) ("Close cases should be resolved by disclosure, not unilaterally by applicant.").
Nevertheless, Gen-Probe has failed to prove that Vysis had the requisite intent to deceive the PTO by withholding this information. It is true that the record indicates that Gene-Trak and Dr. Lawrie may have known that the examples were inoperative. For instance, Dr. Decker testified that he informed Gene-Trak management about his negative results and that he may have shared that information with Dr. Lawrie as well. (Tr. Vol. V at 873:17 and 873:25 where the videotape deposition of Dr. Decker taken on June 1, 2001 was played, including deposition testimony at 88:15-89:2). Similarly, Dr. Kramer informed Gene-Trak as early as 1991 that there were serious impediments to the functioning of Q replicase amplification assays, including reporter probe amplification and possibly the amplification method described in Example 7. (Plaintiff's Exh. 162, letter from Dr. Kramer to Gene-Trak summarizing results of scientific research; Tr. Vol. VI at 1205:21-1208:10). If Gene-Trak and the inventors knew of the inoperativeness of the examples, they should have disclosed that fact to the PTO.
But, their failure to disclose does not amount to a deliberate decision to withhold the information. At worse, it borders on negligence. (E.g., Tr. Vol. V at 977:8-977:21 (explaining abandonment of patent application due to docketing failure)). Negligence does not equate to an intent to deceive. Kingsdown, 863 F.2d at 876. Gen-Probe has not shown any evidence of an actual deliberate decision to withhold the information. And, there is not enough circumstantial evidence to show clearly and convincingly that Vysis or the inventors made that deliberate decision. Without clear and convincing proof of such deliberate decision to deceive, the Court finds that Gen-Probe has not proved the required intent under the inequitable conduct inquiry. Since Gen-Probe has not met one of the two threshold inquiries, it has failed to satisfy its burden of proving inequitable conduct regarding the non-enabled examples.
D. Summary of Inequitable Conduct Rulings
In sum, Gen-Probe has not met its burden of showing by clear and convincing evidence that the patent-in-suit is unenforceable due to inequitable conduct. In each of the three bases for its claim of inequitable conduct, Gen-Probe has failed to show sufficient evidence that there was an intent to deceive and!or that the reasonable examiner would have found the cited references to be material. Consequently, in the exercise of its discretion, the Court concludes that Gen-Probe has not satisfied its burden of proving inequitable conduct by clear and convincing evidence. Judgment shall therefore enter for Vysis on Gen-Probe's claim of inequitable conduct.
IV. Prosecution Laches
At trial, Gen-Probe has argued that the `338 patent is unenforceable because Vysis has unreasonably and prejudicially delayed the prosecution of its patent. See Symbol Techs. Inc. v. Lemelson Med., Educ. Research Found., 277 F.3d 1361, 1363 (Fed. Cir. 2002). The Court has reviewed the jury's advisory verdict on this issue, the evidence presented at trial, and the parties' arguments. For the following reasons, the Court holds that Gen-Probe failed to prove by clear and convincing evidence that prosecution laches renders the `338 patent unenforceable.
A. Facts Underlying the Claim of Prosecution Laches
The parties do not dispute facts associated with the prosecution history of the `338 patent. The genealogy of the `338 patent dates back to the 1980's. On December 21, 1987, Vysis filed U.S. Patent Application Serial No. 136, 920 (the "`920 Application") entitled "Target and Background Capture Methods with Amplification for Affinity Assays." (Plaintiff's Exh. 7, at VI 32 177-32245). On July 20, 1990, the Patent and Trademark Office issued an office action, rejecting all the pending claims in the `920 Application. (Id., at VI 32153-32160). The PTO based its rejection on indefiniteness under 35 U.S.C. § 112 and obviousness under 35 U.S.C. § 103. (Id.). Even after requesting a three-month extension, Vysis failed to respond to the office action. (Tr. Vol. V at 9 12:6-14). The `920 Application thus became abandoned as of January 22, 1991 pursuant to 35 U.S.C. § 133. (Tr. Vol. V at 914:20-914:25).
"Upon failure of the applicant to prosecute the application within six months after any action therein, of which notice has been given or mailed to the applicant, or within such shorter time, not less than thirty days, as fixed by the Director in such action, the application shall be regarded as abandoned by the parties thereto, unless it be shown to the satisfaction of the Director that such delay was unavoidable." 35 U.S.C. § 133 (2001).
On the same day that the `920 Application became abandoned, Vysis filed U.S. Patent Application Serial No. 644, 967 (the "967 Application") as a continuation of the `920 Application with the same claims as its parent application. (Tr. Vol. V at 914:20-9 14:25; Defendant's Exh. OW, `967 Application). On March 12, 1992, the PTO issued an office action, rejecting all the pending claims in the `967 Application pursuant to §§ 103 and 112. Again, Vysis did not respond to the office action and allowed the application to become abandoned pursuant to 35 U.S.C. § 133. (Tr. Vol. V at 929:23-930:7). To overcome the abandonment, Vysis successfully petitioned the PTO to revive the `967 Application to September 14, 1992. (Defendant's Exh. OW).
On September 14, 1992, Vysis submitted the same 24 claims by filing U.S. Patent Application Serial No. 944, 505 (the "`505 Application"), as a continuation of the `967 Application. (Tr. Vol. V at 930:8-930:12). On November 5, 1992, the PTO rejected all the pending claims in the `505 Application for the same reason as it rejected the previous applications. (Plaintiff's Exh. 13, Vysis' internal file of the prosecution history of the `505 application). Vysis then permitted the `505 Application to become abandoned on February 5, 1993, pursuant to 35 U.S.C. § 133. (Tr. Vol. V at 933:22-934:8).
More than a year after the abandonment of the `505 Application, Vysis filed Application Serial No. 238,080 (the "`080 Application"). Filed on May 3, 1994, the `080 Application would ultimately issue as the `338 patent. (Plaintiff's Exh. 3, file wrapper for the `080 Application). Because the PTO denied Vysis' petition to revive the `505 Application in order to provide co-pendeney for U.S. Patent (Plaintiffs Exh. 13), Vysis claimed priority for the application through related co-pending applications, including the `657 Application and its parent applications. (See Apr. 5, 2002 Order Granting Vysis' Motion for a Determination That Effective Filing Date of `338 Patent Is 12/21/87 [Docket #374], at 4-8).
This time, Vysis prosecuted the `080 Application to completion. On May 12, 1998, the `080 Application issued as the `338 Patent. (Plaintiff's Exh. 1, the `338 patent). Thus, the prosecution of the `338 patent lasted about eleven (11) years after Vysis filed the `920 Application.
B. Legal Standards for Prosecution Laches
The Federal Circuit has recently recognized the doctrine of prosecution laches. Symbol Techs. Inc. v. Lemelson Med., Educ. Research Found, 277 F.3d 1361, 1363 (Fed. Cir. 2002). Unfortunately, beyond acknowledging the existence of that doctrine, the court of appeals did not provide any guidance on the legal standards applicable to prosecution laches claims.
For guidance, this Court turns to the Supreme Court cases on which the Federal Circuit relied. In Symbol Tech, the Federal Circuit derived the existence of this doctrine from a series of Supreme Court rulings. Id. (citing Woodbridge v. United States, 263 U.S. 50 (1923), Webster Elec. Co. v. Splitdorf Elec. Co., 264 U.S. 463 (1924) Crown Cork Seal Co. v. Ferdinand Gutmann Co., 304 U.S. 159 (1938), and Gen. Talking Pictures Corp. v. W. Elec. Co., 304 U.S. 175 (1938)).
In Woodbridge, the inventor delayed the issuance of his patent by over nine years after the PTO allowed it to wait until his invention became pecuniarily valuable. Facing those facts and finding laches, the Supreme Court stated that "[a]ny practice by the inventor and applicant for a patent through which he deliberately and without excuse postpones . . . the beginning of the term of his monopoly is an evasion of the statute and defeats its benevolent aim." Woodbridge, 263 U.S. at 56.
In Webster, the applicant filed a divisional application in which he claimed for the first time, over eight years after filing his original application, subject matter originally disclosed but never claimed.Webster, 264 U.S. at 464. The Supreme Court held that such a delay was "unreasonable, and under the circumstances shown by the record, constitutes laches, by which the petitioner lost whatever rights it might otherwise have been entitled to." Id., at 466.
"The Supreme Court [in Crown Cork and Gen. Talking Pictures] subsequently ratified prosecution laches as a defense to an infringement action involving new claims issuing from divisional and continuing applications that prejudice intervening adverse public rights." Symbol Tech., 277 F.3d at 1364 (citing Crown Cork, 304 U.S. at 167-68; Gen. Talking Pictures, 304 U.S. at 183). Although it ratified the existence of prosecution laches, the Supreme Court limited the doctrine's reach to instances where intervening rights occurred. Symbol Tech., 277 F.3d at 1365. Thus, the Supreme Court required some form of prejudicial intervening rights before laches could apply.
The Supreme Court cases thus provide some guidance on the applicable legal standards. Prosecution laches thus apply where the patent applicant delays deliberately, unreasonably and without excuse the issuance of his patent so as to prejudice the intervening rights of another party. And, since the application of this doctrine would render a patent unenforceable, the moving party must provide clear and convincing evidence. See Li Second Family Ltd. Partnership v. Toshiba Corp., 231 F.3d 1373, 1378 (Fed. Cir. 2000). With those legal standards, the Court now turns to their applications to the facts of this case.
At trial, the parties agreed that the "clear and convincing" evidence apply to the prosecution ladies inquiry.
C. Prosecution Laches Does Not Apply In this Case
In this case, Gen-Probe has not presented clear and convincing evidence that prosecution laches should apply in this case. There was a substantial delay between the filing of the `920 Application and in the issuance of the `338 patent. Indeed, almost eleven years elapsed. That delay effectively increased the patent term by another eleven years, providing for more time for the patent to have pecuniary value.
However, there is no clear and convincing evidence that the delay was deliberate or without excuse. Norval Galloway, the attorney who prosecuted the `338 patent and its parent applications, testified that he never intended to delay the prosecution of the patent. (Tr. Vol. V at 1024:10-1024:13). He also stated that he filed those continuation applications because of some personnel changes within Amoco and the extraordinary volume of work assigned to him at the time. (Tr. Vol. V at 919:8-920:3, 934:16-935:23, and 1009:254012:3). In fact, he spent a substantial amount of his time overseeing litigation between Gen-Probe and Amoco Corporation at that time. (Tr. Vol. V at 1023:9-1024:5). Against that testimony, Gen-Probe has only offered the argument that Amoco had twenty to twenty-five patent attorneys and that Amoco could hire more outside counsel to overcome Mr. Galloway's time-constraints. (Tr. Vol. V at 921:7-922:3). Gen-Probe essentially asks the Court to second-guess the budget and personnel decisions that Amoco made at that time, and to infer an intent to delay simply because Amoco refused to reallocate its resources. Such allocation are discretionary decisions based on the Amoco executives' business judgment. The Court thus declines to find that the delay was deliberate or without excuse.
Moreover, Gen-Probe cannot show by clear and convincing evidence that the delay was unreasonable. The `338 patent underwent an eleven year prosecution. Two of Gen-Probe's patents-which were the subject of previous litigations with Amoco — were prosecuted for eleven and fifteen years respectively. (Tr. Vol. V at 1016:21-1020:3 and 1021:2-1022:6; Defendant's Exh. ZU, patent assigned to Gen-Probe and issued after eleven years of prosecution; Defendant's Exh. AAK, patent I assigned to Gen-Probe and issued after fifteen years of prosecution). And, an expert in patent practice and procedure also provided unrebutted testimony that no improper delay occurred in the prosecution of the patent-in-suit. (Tr. Vol. VIII at 1504:8-1506:8). The expert further testified that a person wishing to delay the prosecution intentionally would not have simply refiled the applications as Vysis did, but would have responded to each office action so that the PTO would have to consider the response and then issue another office action. (Tr. Vol. VIII at 1506:9-1509:7). Beyond mere innuendos that Vysis intended to sit on its rights, Gen-Probe has not provided any evidence to show the unreasonableness of the delay. In light of this evidence, the Court finds that the eleven years between filing and issuance of the `338 patent is not unreasonable.
In sum, Gen-Probe has failed to satisfy its burden of proof on its prosecution laches claim. Therefore, the Court concludes that Vysis has not committed prosecution laches in the prosecution of the `338 patent and that judgment as to this declaratory claim should enter in favor of Vysis.
V. Unfair Competition
In addition to the patent arguments, Gen-Probe also raises a claim of unfair competition under state law. Gen-Probe bases its claim of unfair competition on the allegation that Vysis knew or should have known that the claims of the `338 patent were invalid, unenforceable and not infringed. That claim is without merit.
California's unfair competition law ("CUBPA") is broadly phrased to prohibit "any unlawful, unfair or fraudulent business act or practice and unfair, deceptive, untrue or misleading advertising." Cal. Bus. Prof. Code § 17200. "When determining whether a practice is `unlawful,' section 17200 `borrows' violations of other laws, and makes them independently actionable under the [CUBPA]." Aicco, Inc. v. Ins. Co. of North Am. (2001)90 Cal.App. 4th 579 (citing Cel-Tech Communications, Inc. v. Los Angeles Cellular Tel. Co. (1999) 20 Cal. 4th 163, 180). Conduct proscribed by the antitrust law includes "enforc[ing] a patent with knowledge that the patent is invalid or not infringed . . . ." C.R. Bard Inc. v. M3 Sys., Inc., 157 F.3d 1340, 1367 (Fed. Cir. 1998).
First, as discussed above, the Court has concluded that Gen-Probe has not met its burden of showing by clear and convincing evidence that the `338 patent is unenforceable based on inequitable conduct or prosecution laches. See Discussion, Parts III and IV, supra, at 40-56. Since the Court did not find unenforceability, the claim of unfair competition based on alleged knowledge of inequitable conduct or prosecution laches fails.
Second, Gen-Probe has not shown that Vysis knew or should have known that its patent was not infringed. In denying Gen-Probe's motion for summary judgment of non-infringement under the doctrine of equivalents, the Court found that there were genuine issues of material facts concerning the issue of infringement. (Nov. 20, 2001 Order [Docket # 200], at 33-38). There was thus a possibility that the patent was actually infringed. Consequently, the claim of unfair competition based on alleged knowledge of non-infringement also fails.
Finally, at trial, the jury returned a verdict of invalidity based on obviousness and lack of enablement. But, the verdict does not mean that Vysis knew or should have known of its patent's invalidity. A patent is presumed to be valid. 35 U.S.C. § 282. As a result of that statutory presumption, Vysis had reasons to believe that the `338 patent could be valid. Moreover, the fact that Gen-Probe took a license to the patent demonstrates that Vysis was not alone in assuming that the patent could be valid. (Tr. Vol. II at 391:11-391:17; Vol. V at 987:10-987:20). Therefore, Gen-Probe has not proved that Vysis knew or should have know that the `338 patent was invalid.
In sum, Gen-Probe's claim of unfair competition is meritless. Consequently, the Court concludes that judgment shall enter in favor of Vysis on Gen-Probe's claim of unfair competition.
VI. Vysis' Motion for a New Trial
Finally, Vysis requests a new trial under Federal of Civil Procedure 59. In the exercise of its discretion, the Court denies the motion for new trial for the following reasons . . .
First, Vysis contends that it was error for the jury's verdict to find all the claims of the `338 patent invalid. It is true that each claim of a patent is "presumed valid independently of the validity of other claims." 35 U.S.C. § 282. But, all the claims are "invalid once the broad and representative claim [has] been declared invalid, and in the absence of any indication that other claims contained other limitations that might have rendered [non-invalid] the inventions set forth as wholes in those other claims." N.V. Akzo v. E.I. Dupont de Nemours, 810 F.2d 1148, 1152 (Fed. Cir. 1987). In this case, Vysis concedes that its invention consisted of a combination of well-known references on target capture and non-specific amplification. See Discussion, Part II.B.3, supra, at 23. Since all of the claims in the patent stood on that sole inventive premise, a finding supported by substantial evidence that such combination was obvious to one skilled in the art necessarily affected all of the claims in the `338 patent. Similarly, since all the claims included an amplification limitation, the failure to enable that limitation to the full claimed scope in this unpredictable art affected and invalidated the entire `338 patent. See Discussion, Part II.C.2., supra, at 32-37. Hence, the verdict was proper since each and every claim contains the amplification limitation that formed the basis for the invalidity finding. See N.V. Akzo, 810 F.2d at 1152.
Second, Vysis argues that Gen-Probe relied upon the Stabinsky reference for its obviousness case despite having failed to identify that reference as required by law. 35 U.S.C. § 282 ("In actions involving the validity or infringement of a patent the party asserting invalidity or noninfringement shall give notice in the pleadings or otherwise in writing to the adverse party at least thirty days before the trial . . . ."). That argument is erroneous legally and factually. "[S]ection 282 does not dictate an arbitrary or absolute rule barring introduction of relevant, material evidence on the purely formalistic fact that notice of reliance was lacking." Eaton Corp. v. Appliance Valves Corp., 790 F.2d 874, 879-80 (Fed. Cir. 1986). Indeed, on such evidentiary issues under § 282, "[t]he boundaries of the district court's discretion are defined by unfair, prejudicial harm to a party deprived of an adequate opportunity to present its case." Id. In other words, the thirty-days provision of the statute aims to provide adequate and fair notice so that the patentee is not unfairly surprised for the first time at trial. Id., at 879. That provision does not impose a strict and unyielding restriction as Vysis implies. Here, the Court exercised its broad discretion in admitting that evidence and permitting Gen-Probe to rely on the reference because Vysis received adequate and fair notice long before the trial. Vysis knew about the Stabinksy reference since the early 1990's because the PTO cited it as prior art during prosecution in each of the `920, `967, and `505 Applications. Gen-Probe also introduced it as an exhibit at the deposition of Dr. Lawrie on February 15, 2001, more than a year before trial. (Tr. Vol. III at 530:8-530:16). At trial, Vysis did not object when Gen-Probe placed the Stabinsky reference into evidence. (Plaintiff's Exh. 811; Tr. Vol. III at 530:17-53 1:25). As the Court ruled, Vysis has known about this reference well before trial. (Tr. Vol. IX at 1681:11-1681:14). Consequently, the Court rejects Vysis' claims of unfair surprise and prejudice.
Third, Vysis contends that Gen-Probe confused the jury by improperly presenting an erroneous claim construction. But, the record does not support that contention. In fact, the short excerpt cited by Vysis shows that Gen-Probe's argument was not inconsistent with this Court's claim construction. (Tr. Vol. IX at 1682:7-1684:5; Apr. 5, 2002 Order Construing Claim Limitations [Docket #375], at 9-17). Both Gen-Probe and Vysis were at liberty to argue their case to the jury as long as they were consistent with this Court's orders.
Fourth, Vysis complains about a host of evidentiary rulings by listing them without providing any evidentiary support for its objection or showing any prejudice. Under this regional circuit's evidentiary rules as applied by the Federal Circuit, evidentiary rulings are "reviewed for abuse of discretion and should not be reversed absent some prejudice."Defenders of Wildlife v. Bernal, 204 F.3d 920, 927-28 (9th Cir. 2000). Vysis has failed to show any prejudice derived from any of the evidentiary rulings in its litany of alleged errors. In fact, it has shown no evidence of reversible error-or any evidence for that matter — on any of those challenged rulings. Those complains of errors fall flat.
Finally, Vysis asserts that it deserves a new trial because the Court erred in its claim construction of amplification and lacked subject matter jurisdiction over this case. The Court has construed the disputed claim limitation and has reaffirmed it by providing a comprehensive discussion to support its holding. (June 20, 2001 Order [Docket #144]; Nov. 20, 2001 Order [Docket #200)). Having heard and considered all of the trial evidence, the Court determines that its claim construction of that limitation is correct and declines to modify that interpretation. As to Vysis' other major objection, it cannot ask for a new trial while simultaneously asserting that this Court is without jurisdiction over the case. In any case, the Court has already explained at length the reasons why it has jurisdiction over this declaratory judgment action. (Mar. 12, 2002 Order [Docket #334]). Vysis has not shown any evidence contradicting the Court's ruling. In fact, the trial record buttresses the Court's conclusion that there was a reasonable apprehension of litigation and thus jurisdiction. (E.g., Tr. Vol. II at 358:2-362:11 and 366:10-371:24).
A trial court may grant a new trial if the verdict is "contrary to the clear weight of the evidence, or is based upon evidence which is false, or to prevent, in the sound discretion of the trial judge, a miscarriage of justice." Richardson, 868 F.2d at 1245. The decision to grant or deny a new trial rests within the sound discretion of the court. Allied Chemical Corp., 449 U.S. at 36. Having considered this motion in light of all the evidence presented at trial, the Court exercises its broad discretion in denying Vysis' motion for a new trial.
CONCLUSION
Having considered the controlling law, the parties' arguments, and the totality of the evidence, the Court (1) DENIES Vysis' motion for judgment as a matter of law an for new trial [Docket #448], (2) GRANTS Vysis' motion for entry judgment on equitable issues [Docket #448], and (3) DENIES Gem-Probe's motions for entry of judgment on the equitable issues [Docket #450-452]. Specifically, the Court holds that:
In ruling on these post-trial motions, the Court has reviewed the entire record of this case and all the evidence presented at trial. For reasons of judicial efficiency, this Order only cites to portions of the record and the evidence that are most germane to the issues raised by the parties. Accordingly, although it has not cited every exhibit or testimony that may be relevant to those issues, the Court has considered the totality of the evidence in reaching the present rulings.
• Because substantial evidence supports the jury's verdict on non-infringement, the judgment entered in favor of Gen-Probe on the issue of non-infringement remains undisturbed.
• Because the `338 patent is invalid based on obviousness and lack of enablement in light of the jury's verdict and the controlling law, the judgment in favor of Gen-Probe on the issues of invalidity remains unchanged.
• Because Gen-Probe has not proved by clear and convincing evidence that Vysis has committed inequitable conduct in prosecuting the `338 patent, judgment shall enter in favor of Vysis on Gen-Probe's claim of inequitable conduct.
• Because Gen-Probe has not shown that Vysis unreasonably and deliberately delayed without excuse the prosecution of its patent, judgment shall enter in favor of Vysis on Gen-Probe's claim of prosecution laches.
• Because Gen-Probe has not shown that Vysis committed unfair competition, judgment shall enter in favor of Vysis on Gen-Probe's state law claim of unfair competition.
• Having reviewed the record and the evidence, the Court exercises its discretion in denying Vysis' motion for a new trial.
The Clerk of Court shall enter judgment as to the three equitable claims and close this docket.
Finally, the Court commends the parties' attorneys for their performance in the prosecution of this case. The Court particularly compliments the attorneys for the high quality of their briefs, their presentation of the evidence, their ability to explain a complex technology to a lay jury, their oral advocacy, and their overall courtesy and professionalism during the course of this litigation.