Board of Patent Appeals and Interferences
Patent and Trademark Office (P.T.O.)
*1 EX PARTE N. CHUNG SIZTO AND CYNTHIA G. ROUX
Appeal No. 87-1346
March 22, 1988
Application for Patent filed March 27, 1984, Serial No. 593,762. Calibration Device For Heterogeneous Immunoassay.
Theodore J. Leitereg for Appellants.
Primary Examiner--Christine M. Nucker.
Before Seidleck, W. Smith and Skinner
This is an appeal from the final rejection of claims 1-20, all of the claims in the application.
Appellants' invention relates to an improved immunoassay method and device with a calibration surface employing a receptor that is capable of specific binding to a conjugate of a catalyst with a member of an immunological pair, but is substantially incapable of binding to the catalyst or the member of the immunological pair apart from the conjugate. Claims 1 and 15 are representative:
1. In a method for determining the presence in a sample of an analyte, which analyte is a member of a specific binding pair ("mip") consisting of ligand and receptor ("antiligand"), said method comprising the step of:
(a) contacting with said sample (i) at least one catalyst including a catalyst bound to a mip ("catalyst-bound-mip") and (ii) a solute which is catalytically transformed by a catalyst bound to a mip-containing measurement first surface to produce a change in a detectable signal at said first surface in proportion to the amount of catalyst-bound-mip bound to said first surface, wherein said catalyst-bound-mip binds to said first surface in proportion to the amount of analyte in said sample, and (iii) a calibration second surface, adjacent to said first surface, to which second surface catalyst becomes bound in an amount which provides substantially predetermined ratios to the amount of said catalyst bound to said first surface, whereby the ratio of the change in signal at said second surface to the change in signal at said first surface is related to the amount of analyte in said sample, and
(b) determining said ratio,
the improvement which comprises employing on said second surface a receptor for said catalyst-bound-mip, said receptor being capable of specific binding to said catalyst-bound-mip and being substantially incapable of binding to said catalyst or said mip apart from said catalyst-bound-mip.
15. An internally calibrated diagnostic device comprising a support, a measurement surface of a porous material, a calibration surface of a porous material in close proximity to said measurement surface, a member of a specific binding pair ("mip") non-diffusively bound to said measurement surface, and a receptor non-diffusively bound to said calibration surface, said receptor being capable of specific binding to a conjugate of an enzyme and a mip but substantially incapable of binding to said enzyme or said mip apart from said conjugate.
Decker et al (Decker) 4,230,683 Oct. 28, 1980
Litman et al (Litman A) 4,533,629 Aug. 6, 1985
(filed May 4,
Litman et al (Litman B) 4,540,659 Sep. 10, 1985
(filed Jul. 16,
Jhsani et al (Jhsani) British 2,098,730 Nov. 24, 1982
Litman et al (Litman C), "An Internally
Referenced Test Strip Immunoassay for
Morphine", Clinical Chemistry, Vol. 29(9), pp.
*2 Claims 1-20 stand rejected on the basis of 35 USC 103 as unpatentable over Litman A, B and C taken collectively in view of Decker or Jhsani. Claims 1-20 stand rejected on the basis of 35 USC 112, first paragraph, as based on insufficient disclosure in that the specification fails to provide an enabling disclosure and fails to adequately teach how to make and use the invention. Claims 1-4 also stand rejected on the basis of 35 USC 112, first paragraph, as exceeding the scope of the enabling disclosure in that the specification is enabling only for catalysts which are enzymes.
The Rejection Under 35 USC 103
The examiner and appellants agree that the subject matter of the claims on appeal is an improvement over the disclosures of Litman A, B and C. The improvement resides in the receptor on the calibration surface, which selectively binds to a conjugate of a catalyst with a member of an immunological pair (mip), but does not bind to the catalyst or the mip apart from the conjugate. The examiner urges that Decker and Jhsani teach assay methods which employ a hapten-label antibody and an anti-hapten antibody, and that these anti-hapten antibodies of the prior art have functions and characteristics similar to those of appellants' receptor materials. We will not sustain this rejection.
Decker teaches a hapten-antibody conjugate and a labeled anti-hapten antibody. The anti-hapten antibody binds to the hapten portion of the conjugate and the antibody portion of the conjugate reacts with an antigen bound to a solid support. Jhsani discloses a method of detecting an antigenic substance in which a primary antibody to the substance is raised, linked to a hapten and then reacted with the antigenic substance. The primary antibody is then bound to a specific bridging antibody, which is subsequently linked to a detecting agent. We are unable to find any suggestion in either of these disclosures, and the examiner has pointed to no specific teaching, to the effect that there is any selective binding of the receptor to the entire conjugate without binding to the elements apart from the conjugate. Neither reference recognizes that degradation of the conjugate would occur or that such degradation would affect the immunoassay. In view of the lack of suggestion or motivation in the prior art to prepare a calibration surface receptor capable of selective binding to catalyst-bound mip conjugate we find that no prima facie case of obviousness has been established, and this rejection of claims 1-20 is reversed.
The Rejection Under 35 USC 112 (Claims 1-20)
The examiner contends that appellants' disclosure with respect to the preparation of antibody specific to the conjugate is inadequate in that a general outline of the methodology is not shown, and that non-reactivity with the individual components of the conjugate has not been demonstrated. However, we find appellants' arguments in this regard persuasive. Appellants have referred to a well-known method for preparing monoclonal antibodies at page 13, line 14, of the specification, and have subsequently outlined the general methodology relevant to the invention. As the examiner concedes, the methodology for preparing monoclonal antibodies is generally known and routine. In Example 2 of the specification appellants have also set forth the preparation of a penicilloic acid-bovine serum albumin conjugate, the myeloma cell line used for cell fusion, the ELISA assay used to isolate and clone the anti-HRP-PA and the preparation of the desired surfaces. Further, we are convinced that appellants' Examples 6 and 9 sufficiently describe the specificity of the binding by the receptor materials of the invention. In the absence of evidence that the disclosure is inadequate, we are of the opinion that one of ordinary skill in this art would have been enabled to make and use the specific receptor materials of the claims on appeal. This rejection of claims 1-20 is therefore reversed.
The Rejection Under 35 USC 112 (Claims 1-4)
*3 The examiner has taken the position that the single example disclosing an enzyme catalyst is not sufficient to support the claims to catalysts in general. Appellants have incorporated into the specification by reference those portions of U.S. Patent No. 4,160,645 which disclose a "wide variety" of non-enzymatic catalysts which may be employed. However, as the examiner has noted, this wide variety includes compositions which are vastly different from enzymes. They include quinones, quinonediimines, biaryls, heterocyclics, metal complexes and electron transfer agents. We find ourselves in agreement with the examiner that where the enzyme and non-enzyme catalysts are so divergent, it is not unreasonable to require a reasonable number of examples in support of the broad claim. While we agree with appellants' citation of the general rule to the effect that there need only be an enumeration of a sufficient number of members of a diverse group, we also are persuaded that where, as here, there is unpredictability as to the characteristics of conjugates prepared from, e.g., metal complexes and electronic transfer agents as compared to enzymes, the scope of enablement must be commensurate with the scope of the claims. In re Fisher, 427 F.2d 833, 166 USPQ 18 (CCPA 1970). We find such enablement for catalysts other than enzymes lacking.
Appellants point out that the invention broadly relates to a method, and not a specifically active antibody. However, the receptors of the invention are specific to catalyst-mip conjugates. Given this specificity, it is necessary to inquire into the object of the specific activity, i.e., the conjugate. Thus the nature of the catalyst becomes critical to ability to make and use the invention. Appellant also points out that the specification at page 11, lines 21-29, refers to non-enzymatic catalysts. This passage appears to us to indicate that the presence of an enzyme is required in the conjugate, even when non-enzymatic catalysts are involved. We do not find this persuasive enablement for a wide variety of catalysts other than enzymes.
Under the provision of 37 CFR 1.196(b), we reject claim 13 on the basis of 35 USC 112, first paragraph, for the reasons set forth in the preceding rejection of claims 1-4. Claim 13 likewise recites a catalyst as part of the conjugate, and the disclosure is enabling only for claims limited to catalysts which are enzymes.
Any request for reconsideration or modification of this decision by the Board of Patent Appeals and Interferences based upon the same record must be filed with one month from the date hereof (37 CFR 1.197).
With respect to the new rejection under 37 CFR 1.196(b), should appellants elect the alternate option under that rule to prosecute further before the primary examiner by way of amendment or showing of facts, or both, not previously of record, a shortened statutory period for making such response is hereby set to expire one month from the date of this decision. In the event appellants elect this alternate option, in order to preserve the right to seek review under 35 USC 141 or 145 with respect to the affirmed rejection, the effective date of the affirmance is deferred until conclusion of the prosecution before the examiner unless, as a mere incident to the limited prosecution, the affirmed rejection is overcome.
*4 If the appellants elect prosecution before the examiner and this does not result in allowance of the application, abandonment or a second appeal, this case should be returned to us for final action on the affirmed rejection, including any timely request for reconsideration thereof.
37 CFR 1.136(a) does not apply to the times for taking any subsequent action in connection with this appeal.
AFFIRMED-IN-PART. 37 CFR 1.196(b).
BOARD OF PATENT APPEALS AND INTERFERENCES
James A. Seidleck
William F. Smith
William A. Skinner