Talk:Hybritech v. Monoclonal Antiboties, 802 F.2d 1375 (1986)

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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