Board of Patent Appeals and Interferences
Patent and Trademark Office (P.T.O.)
*1 EX PARTE CLEMENS SORG, GERD BURMEISTER, LAJOS TARCSAY AND WALTER
Appeal No. 91-2574
January 10, 1992
Application for Patent filed May 17, 1988, Serial No. 196,793, a Continuation of Serial No. 734,641 filed May 16, 1985. Lymphokine in Pure Form, Novel Monoclonal Antibodies, Hybridoma Cell Lines, Processes and Applications.
JoAnn Villamizar et al. for appellants
Primary Examiner--Margaret Moskowitz
This appeal is from the examiner's final rejection of claims 13 to 17, 20 to 24, 33 and 42 to 50, which are all of the claims remaining in the application. Illustrative claim 13 is reproduced below:
13. Monoclonal antibodies which specifically bind to human macrophage migration inhibition factor of approximately 8, 14, 28 and 45 kg/mole molecular weight, and derivatives thereof retaining their specificity for the antigenic determinants of human macrophage migration inhibition factor selected from the group consisting of monoclonal antibody fragments, radioactively labelled monoclonal antibodies, and monoclonal antibody conjugates with biotin, avidin or enzymes.
References relied on by the examiner on appeal are: Brandt et al. (Brandt) 4,299,814 Nov. 10, 1981 Kohler et al. (Kohler), "Continuous cultures of fused cells secreting antibody of predefined specificity," Nature, 356, pp. 495-497 (1975).
Burmeister et al. (Burmeister), "Chemical characterization of human macrophage migration inhibitory factors," Immunology, 160(1), p. 15 (1981).
A newly cited reference which shall be discussed in the following opinion is:
Goding, "Antibody Production by Hybridomas," J. of Immunological Methods, 39, pp. 285-286 (1980).
All of the appealed claims have been finally rejected under 35 U.S.C. 103 as being unpatentable over the combined teachings of Brumeister, Kohler and Brandt. We shall affirm this rejection.
Despite careful consideration of all of appellants' arguments on appeal, we agree substantially with the position set forth by the examiner in her answer on appeal. In the interest of completeness and for emphasis, however, we shall add the following additional comments.
Resolution of the issue of obviousness in cases of the present type is not readily subject to broad generalizations, but in each case those issues must be decided on the specific facts present in that case. [FN1] To the extent that prior decisions can provide guidance, however, we find the decision relied on by the examiner, Ex parte Erlich, 3 USPQ2d 1011 (BPAI 1986), to be more relevant to the facts in the present case than the decision relied on by appellants, Ex parte Old, 229 USPQ 196 (BPAI 1985). Of possibly even greater relevance because of an even closer similarity on its facts is the more recent decision of Ex parte Sugimoto, 14 USPQ2d 1312 (BPAI 1988), which we shall discuss at greater length.
*2 In Sugimoto, the monoclonal antibodies being produced bore no particular similarity to the antibodies produced in the reference relied on by the examiner, i.e., the stimulating immunogens were not particularly related, whereas in Erlich they were two different types of interferon. The facts in the present case would seem to lie somewhere between. The examiner has relied on the Brandt disclosure to illustrate the fact that MIF was known to be used in processes to produce polyclonal antibodies. By citing the Erlich case, she has in effect made of record the fact that the hybridoma technique of producing monoclonal antibodies had been applied to various types of interferon, which have in common with Brandt's and the here claimed MIF that they are of the class of substances known as lymphokynes. Both the Erlich and Sugimoto decisions are consistent, as this one shall be, with our reviewing court's recognition that methods for obtaining and screening monoclonal antibodies were well known in 1980.
Appellants have correctly stated in their specification (page 4), with regard to the application of the hybridoma technique, that "with each new example specific problems arise that require adaptation of the technique to the particular case." The legal issue reflected in that statement is whether or not the adaptations required involve the application of more than ordinary skill in the relevant art, i.e., would not have been obvious under 35 U.S.C. 103. In the present case, despite appellants' arguments in the brief and reply brief, we find that no convincing evidence has been presented that any unobvious adaptations were required.
The use of conjugates with sheep erythrocytes was disclosed in appellants' specification (page 14) only as a preference. This does not support appellants' present arguments that such use was essential to their success, and this inconsistency could give rise to some question of the enabling nature of appellants' specification. Even if appellants' disclosure did support their present argument, the adaptation relied on probably would not require a conclusion of unobviousness. We have supplemented the record with the Goding review article to illustrate that it was already known that "soluble proteins are often very poorly immunogenic in aqueous solution" and that it was generally known to use "some kind of adjuvant" to boost immunogenicity. The Kohler reference itself illustrates that sheep erythrocytes were known to be highly immunogenic. Thus, their use as conjugates for the MIF per se could have been considered an obvious technique. We should emphasize, however, that appellants' argument based on this issue has been found to be unpersuasive because of its lack of support in the specification or anywhere else on the record, and we have elaborated on this issue mainly in the event that this subject matter should be further prosecuted before the examiner, e.g., in a continuing application.
*3 In a similar fashion to the issue discussed above, appellants' arguments concerning the criticality of the use of a specific multistep screening procedure for hybridomas is completely inconsistent with their disclosure at page 16 of the specification, which clearly sets forth that any one of a number of generally known assays may be used, alone or in combination.
For the reasons given by the examiner in the answer on appeal and those discussed above, the rejection of all of the claims on appeal is affirmed.
No time period for taking any subsequent action in connection with this appeal may be extended under 37 CFR 1.136(a). See the final rule notice, 54 F.R. 29548 (July 13, 1989), 1105 O.G. 5 (August 1, 1989).
BOARD OF PATENT APPEALS AND INTERFERENCES
John T. Goolkasian
William F. Smith
FN1. Appellants' en cognizance of this fact in their reply brief.