Talk:Hybritech v. Monoclonal Antiboties, 802 F.2d 1375 (1986)
Scientists and clinicians have long employed the ability of antibodies to recognize and complex with antigens as a tool to identify or label particular cells or molecules and to separate them from a mixture. Their source of antibodies has been primarily the serum separated from the blood of a vertebrate immunized or exposed to the antigen.
Immunoassays, the subject matter of the '110 patent, are diagnostic methods for determining the presence or amount of antigen in body fluids such as blood or urine by employing the ability of an antibody to recognize and bind to an antigen. Generally, the extent to which the antibody binds to the antigen to be quantitated is an indication of the amount of antigen present in the fluid. Labelling the antibody or, in some cases, the antigen, with either a radioactive substance, I125, or an enzyme makes possible the detection of the antibody-antigen complex.
Hybritech sued Monoclonal March 2, 1984, for damages and an injunction alleging that the manufacture and sale of Monoclonal's diagnostic kits infringed the '110 patent.
The district court also invalidated the patent on various grounds based on 35 U.S.C. Sec. 112, first and second paragraphs, as hereinafter discussed.A.
B. The Claimed Subject Matter of the '110 Patent 50 Hybritech argues that the district court's determination that there is no credible evidence of conception or reduction to practice of the '110 invention before May 1980 is error because Dr. David's laboratory notebooks, Nos. 21 and 24, clearly show successful sandwich assays using monoclonal antibodies in August, September, and October of 1979. At the least, argues Hybritech, the invention was conceived in January of 1979, long before Drs. Ruoslahti, Engvall, and Uotila began work on a sandwich assay using monoclonal antibodies, and diligence was thereafter exercised until constructive reduction to practice occurred by the filing of the '110 patent application on August 4, 1980.
Under 35 U.S.C. Sec. 282, a patent is presumed valid, and the one attacking validity has the burden of proving invalidity by clear and convincing evidence.
Hybritech's claim of conception, generally, is evidenced by the sometimes sparsely documented work of a start-up company whose first small advances evolved into the myriad activities of a mature company with efforts directed toward developing the claimed invention by first employing the Kohler and Milstein technology to produce the necessary monoclonal antibodies and using those antibodies in diagnostic sandwich assay kits. There is no doubt that exploiting monoclonal antibodies for use in sandwich assays was one of the major objectives of Hybritech.
A section 103 obviousness determination--whether the claimed invention would have been (not "would be" as the court repeatedly stated because Monoclonal's pretrial papers used that improper language) obvious at the time the invention was made is reviewed free of the clearly erroneous standard although the underlying factual inquiries--scope and content of the prior art, level of ordinary skill in the art,3 and differences between the prior art and the claimed invention--integral parts of the subjective determination involved in Sec. 103, are reviewed under that standard.
Objective evidence such as commercial success, failure of others, long-felt need, and unexpected results must be considered before a conclusion on obviousness is reached and is not merely "icing on the cake," as the district court stated at trial.
The district court's finding that Kohler and Milstein developed a method for producing monoclonal antibodies in vitro is correct, but that finding proves no more; although it made possible all later work in that it paved the way for a supply of monoclonal antibodies, it indisputably does not suggest using monoclonal antibodies in a sandwich assay in accordance with the invention claimed in the '110 patent.
The trial court's finding that the "sudden availability of monoclonals" was the reason for the commercial success of Hybritech's diagnostic kits (Finding 11) is unsupported by the record and clearly erroneous. Monoclonal admits that monoclonal antibodies were available in the United States in 1978, and the evidence clearly reflects that. Thus, at least three years passed between the time monoclonal antibodies were available in adequate supply and the time Hybritech began selling its kits. Especially in the fast-moving biotechnology field, as the evidence shows, that is anything but sudden availability. 97
With respect to the objective indicia of nonobviousness, while there is evidence that marketing and financing played a role in the success of Hybritech's kits, as they do with any product, it is clear to us on the entire record that the commercial success here was due to the merits of the claimed invention. It cannot be argued on this record that Hybritech's success would have been as great and as prolonged as admittedly it has been if that success were not due to the merits of the invention. The evidence is that these kits compete successfully with numerous others for the trust of persons who have to make fast, accurate, and safe diagnoses. This is not the kind of merchandise that can be sold by advertising hyperbole.
"The specification ... shall set forth the best mode contemplated by the inventor of carrying out his invention." 35 U.S.C. Sec. 112. Because not complying with the best mode requirement amounts to concealing the preferred mode contemplated by the applicant at the time of filing, in order to find that the best mode requirement is not satisfied, it must be shown that the applicant knew of and concealed a better mode than he disclosed. DeGeorge v. Bernier, 768 F.2d 1318, 1324, 226 USPQ 758, 763 (Fed.Cir.1985) (quoting with approval In re Sherwood, 613 F.2d 809, 204 USPQ 537 (CCPA 1980)). The only evidence even colorably relating to concealment is testimony by various Hybritech employees that sophisticated, competent people perform the screening and that the screening process is labor-intensive and time-consuming. It is not plausible that this evidence amounts to proof of concealment of a best mode for screening or producing monoclonal antibodies for use in the claimed '110 process, and therefore we are of the firm conviction that the district court's finding that the best mode requirement was not satisfied is clearly erroneous.
The evidence of record indisputably shows that calculating affinity was known in the art at the time of filing, and notwithstanding the fact that those calculations are not precise, or "standard," the claims, read in light of the specification, reasonably apprise those skilled in the art and are as precise as the subject matter permits.
The record also shows that Blakemore, who testified extensively for Monoclonal that the claimed invention would have been obvious, never used monoclonal antibodies in sandwich assays at Bio-Rad before 1980.
It bears repeating that it is crucial that counsel set forth the law accurately. More particularly, it is the duty of counsel to impart to the judge that the obviousness question properly is whether the claimed invention as a whole would have been obvious to one of ordinary skill in the art at the time the invention was made, and that the district court must expressly make the three factual determinations required by Graham and consider objective evidence of obviousness before the legal conclusion of obviousness vel non is made. Submitting to the court language like "any differences ... would have been obvious," as was done here, violates the axiom that the question is not whether the differences would have been obvious but the claimed invention as a whole. Furthermore, arguing that "it would be obvious" rather than that it would have been obvious shifts the court's focus to the wrong period of time, namely to a time long after the invention was made, in which, more likely than not, the prior art and the level of ordinary skill in the art are more advanced. See 35 U.S.C. Sec. 103
Immunoassays, the subject matter of the '110 patent, are diagnostic methods for determining the presence or amount of antigen in body fluids such as blood or urine by employing the ability of an antibody to recognize and bind to an antigen.
The '110 patent, application for which was filed August 4, 1980, issued March 8, 1983, with claims defining a variety of sandwich assays using monoclonal antibodies.
The district court held that the claimed subject matter of the '110 patent was neither conceived nor actually reduced to practice before May 1980, and was anticipated under Sec. 102(g) by the actual reduction to practice of the invention by Drs. Uotila and Ruoslahti at the La Jolla Cancer Research Foundation (LJCRF) as early as November of 1979 and by the actual reduction to practice of the invention by Drs. Oi and Herzenberg (Oi/Herzenberg work) at the Stanford University Laboratory as early as July 1978, later published in December of 1979. 22 The district court also held the claims of the '110 patent invalid for obviousness from the Oi/Herzenberg work in view of (1) a February 1979 article by M.E. Frankel and W. Gerhard (Frankel article) which discloses high- affinity monoclonal antibodies, and apparently in view of numerous other references including; (2) the work of Nobel Prize winners G. Kohler and C. Milstein disclosing a Nobel Prize-worthy method for producing monoclonal antibodies in vitro (outside the body) published in an August 7, 1975...
Rule 52(a) "ensures care in the preparation of an opinion ... and provides appellate courts with the benefit of the District Court's insights into a case," Pentec, Inc. v. Graphic Controls Corp., 776 F.2d 309, 318, 227 USPQ 766, 772 (Fed.Cir.1985) (Harvey, Senior District Judge, concurring) by requiring a district court to "find the facts specially and state separately its conclusions of law thereon."
"A finding is clearly erroneous when, although there is evidence to support it, the reviewing court on the entire evidence is left with the definite and firm conviction that a mistake has been committed." United States v. United States Gypsum Co., 333 U.S. 364, 395, 68 S.Ct. 525, 542, 92 L.Ed. 746 (1948). "This standard plainly does not entitle a reviewing court to reverse the finding of the trier of fact simply because it is convinced that it would have decided the case differently." Anderson, supra, 105 S.Ct. at 1511. In other words, "if the district court's account of the evidence is plausible in light of the record viewed in its entirety" or "where there are two permissible views of the evidence," the factfinder cannot be clearly erroneous.
Under 35 U.S.C. Sec. 282, a patent is presumed valid, and the one attacking validity has the burden of proving invalidity by clear and convincing evidence.
Section 102(g) states that a person shall be entitled to a patent unless "before the applicant's invention thereof the invention was made in this country by another who had not abandoned, suppressed, or concealed it." Section 102(g) "relates to prior inventorship by another in this country" and "retains the rules governing the determination of priority of invention...." Kimberly-Clark Corp. v. Johnson & Johnson, 745 F.2d 1437, 1444, 223 USPQ 603, 606 (Fed.Cir.1984) (quoting P.J. Federico, Commentary on the New Patent Act, 35 USCA page 1, at 19 (1954)). Section 102(g) says: "In determining priority of invention there shall be considered not only the respective dates of conception and reduction to practice of the invention, but also the reasonable diligence of one who was first to conceive and last to reduce to practice, from a time prior to conception by the other." 59
Conception is the "formation in the mind of the inventor, of a definite and permanent idea of the complete and operative invention, as it is hereafter to be applied in practice." 1 Robinson On Patents 532 (1890); Coleman v. Dines, 754 F.2d 353, 359, 224 USPQ 857, 862 (Fed.Cir.1985). Actual reduction to practice requires that the claimed invention work for its intended purpose, see, e.g., Great Northern Corp. v. Davis Core & Pad Co., 782 F.2d 159, 165, 228 USPQ 356, 358, (Fed.Cir.1986), and, as has long been the law, constructive reduction to practice occurs when a patent application on the claimed invention is filed.
We are left with the definite and firm conviction that a mistake has been committed because the district court's account of the evidence that "there was no credible evidence of conception before May 1980" is insupportable. There is such evidence. The laboratory notebooks, alone, are enough to show clear error in the findings that underlie the holding that the invention was not conceived before May 1980. That some of the notebooks were not witnessed until a few months to one year after their writing does not make them incredible or necessarily of little corroborative value.
Hybritech laboratory notebooks and the uncontradicted testimony of Dr. David and Mr. Greene show that development of the claimed invention proceeded diligently through the rest of 1979 and 1980, there being absolutely no evidence of record nor even argument by Monoclonal that Hybritech was not diligent in its efforts to reduce to practice the claimed invention during the period January 1979 to the '110 application filing date of August 4, 1980. We therefore hold as a matter of law that Hybritech's conception, which was before LJCRF conceived the claimed invention, coupled by diligence to its constructive reduction to practice by the filing of the '110 application, entitle Hybritech to priority over LJCRF. See 35 U.S.C. Sec. 102(g). The work of LJCRF is therefore not prior art. 72
A section 103 obviousness determination--whether the claimed invention would have been (not "would be" as the court repeatedly stated because Monoclonal's pretrial papers used that improper language) obvious at the time the invention was made is reviewed free of the clearly erroneous standard although the underlying factual inquiries--scope and content of the prior art, level of ordinary skill in the art,3 and differences between the prior art and the claimed invention--integral parts of the subjective determination involved in Sec. 103, are reviewed under that standard. Objective evidence such as commercial success, failure of others, long-felt need, and unexpected results must be considered before a conclusion on obviousness is reached and is not merely "icing on the cake," as the district court stated at trial. See Lindemann, supra, 730 F.2d at 1461, 221 USPQ at 488; Stratoflex, Inc. v. Aeroquip Corp., 713 F.2d 1530, 218 USPQ 871 (Fed.Cir.1983); Kansas Jack, Inc. v. Kuhn, 719 F.2d 1144, 219 USPQ 856 (Fed.Cir.1983); W.L. Gore & Associates v. Garlock, Inc., 721 F.2d 1540, 220 USPQ 303, 314 (Fed.Cir.1983). 78
Having considered the evidence of nonobviousness required by Sec. 103 and Graham, supra, we hold, as a matter of law, that the claimed subject matter of the '110 patent would not have been obvious to one of ordinary skill in the art at the time the invention was made and therefore reverse the court's judgment to the contrary. The large number of references, as a whole, relied upon by the district court to show obviousness, about twenty in number, skirt all around but do not as a whole suggest the claimed invention, which they must, to overcome the presumed validity, Lindemann, 730 F.2d at 1462, 221 USPQ at 488, as a whole.
"The specification ... shall set forth the best mode contemplated by the inventor of carrying out his invention." 35 U.S.C. Sec. 112. Because not complying with the best mode requirement amounts to concealing the preferred mode contemplated by the applicant at the time of filing, in order to find that the best mode requirement is not satisfied, it must be shown that the applicant knew of and concealed a better mode than he disclosed.
The judgment of the district court holding the patent in suit invalid is reversed in all respects, and the case is remanded for a determination of the issue of infringement which the court held was moot. 114 REVERSED AND REMANDED.