Board of Patent Appeals and Interferences
Patent and Trademark Office (P.T.O.)
*1 EX PARTE MICHAEL M. JOCHIM AND SUZANNE C. JONES
Appeal No. 88-0789
December 22, 1988
Application for Patent filed January 12, 1984, Serial No. 06/570,155. Monoclonal Antibodies To Bluetongue Virus Antigen.
M. Howard Silverstein for appellant
Supervisory Patient Examiner--Thomas G. Wiseman
Before Goldstein, Pellman and W. Smith
This is an appeal from the final rejection of claims 29 through 31. Claims 17 through 26 and 28 are in the application and have been allowed by the examiner. Representative of the allowed claims are claims 20, 21, 22 and 23 which are appended to this decision.
Claims 29 through 31 read as follows:
29. A hybridoma which produces monoclonal antibody which reacts with bluetongue virus (BTV) antigen of serotypes 2, 10, 11, 13 and 17 as shown by indirect fluorescent antibody testing (IFAT), and does not react with epizootic hemorrhagic disease virus (EHDV) antigen serotypes 1 and 2 as shown by IFAT.
30. A monoclonal antibody which reacts with bluetongue virus (BTV) antigen of serotypes 2, 10, 11, 13 and 17 as shown by indirect fluorescent antibody testing (IFAT), and does not react with epizootic hemorrhagic disease virus (EHDV) antigen serotypes 1 and 2 as shown by said IFAT.
31. A method of producing a hybridoma which secrets (sic) monoclonal antibody which is group specific to bluetongue virus (BTV) antigen and does not react with epizootic hemorrhagic disease virus (EHDV) antigen, comprising immunizing a mouse with BTV as follows: injecting said mouse with 2 intraperitoneal injections of 3.2 x 106 plague (sic) forming units (PFU) of BTV, given approximately 5 weeks apart; after 2 weeks, injecting said mouse with 1.6 x 106 PFU of BTV intravenously; resting said mouse 20 weeks and reinjecting it with 1.6 x 106 PFU of BTV intravenously; removing the spleen from said mouse 3 days after the last injection of BTV; and thereafter fusing cells from said spleen with mouse myeloma cells.
The examiner has not relied upon any references in rejecting claims 29 through 31. Rather, claims 29 and 30 stand rejected under 35 USC § 112, first paragraph as being nonenabled and claim 31 stands rejected under 35 USC § 112, second paragraph as failing to particularly point out and distinctly claim the subject matter which appellants regard as their invention. We affirm-in-part.
REJECTION UNDER 35 USC § 112, FIRST PARAGRAPH
Claim 29 is directed to a hybridoma which produces a monoclonal antibody which reacts with bluetongue virus (BTV) antigen of the specified serotypes and does not react with epizootic hemorrhagic disease virus (EDHV) antigen of the specified serotypes. Claim 30 is directed to the monoclonal antibody which has the same reactivity. These claims are generic and encompass any hybridoma which produces the recited monoclonal antibody and any monoclonal antibody having the specified reactivity.
*2 The hybridomas and monoclonal antibodies of the disclosed invention are made by a method which parallels the classical method disclosed by Kohler and Milstein. The disclosed method differs from that of Kohler and Milstein, inter alia, in that the mice are injected with BTV to stimulate the lymphocyte population to produce antibodies according to a very specific immunization schedule and the spleens from the immunized mice are removed or harvested three days after the last intravenous inoculation of virus for subsequent cell fusion. See page 4, lines 16-22 and page 9, lines 1-27 of the present specification.
The claims which have been allowed by the examiner are all limited to the specific immunization schedule and spleen harvesting times set forth in the disclosure of this application. In response to a prior art rejection which was based in part on the classical method of Kohler and Milstein for producing monoclonal antibodies and in part on knowledge of the utility of polyclonal serum raised against BTV, co-appellant Dr. Michael Jochim filed a declaration under 37 CFR 1.132. See Paper No. 7 filed October 25, 1986. Dr. Jochim establishes his credentials in the declaration as a recognized expert, both nationally and internationally, in the area of BTV research. In his declaration, Dr. Jochim states that one cannot predict antibody response of an animal species to BTV from results obtained from testing a different species and that each species is different when it comes to the development of an antibody response to BTV. Dr. Jochim further states:
The antibody response of different species to injection of BTV is only one part of the unpredictability of producing the desired antibodies to BTV antigen. Other important factors in the production of antibodies are the method (route) of injection, type (source) of inoculum, level (amount) of inoculum, time schedule for inoculation, and the time after inoculation when mouse spleens are used for cell fusion. Success or failure can depend on the development of the critical protocol.
The prior aret rejections of record were withdrawn by the examiner after Dr. Jochim's declaration was again presented in Paper No. 10, filed January 20, 1987.
Turning to the examiner's rejection under § 112, first paragraph, we note the court's statement in In re Marzocchi, 58 CCPA 1069, 439 F.2d 220, 169 USPQ 367 (1971):
As a matter of Patent Office practice, then, a specification disclosure which contains a teaching of the manner and process of making and using the invention in terms which correspond in scope to those used in describing and defining the subject matter sought to be patented must be taken as in compliance with the enabling requirement of the first paragraph of § 112 unless there is reason to doubt the objective truth of the statements contained therein which must be relied on for enabling support. Assuming that sufficient reason for such doubt does exist, a rejection for failure to teach how to make and/or use will be proper on that basis; such a rejection can be overcome by suitable proofs indicating that the teaching contained in the specification is truly enabling. [emphasis in original]
*3 Here, Dr. Jochim's declaration provides an ample basis to question the scope of enablement for claims 29 and 30. Dr. Jochim states in his declaration that the immunization and spleen harvesting schedule which is used in the classical method of Kohler and Milstein to obtain the hybridomas and monoclonal antibodies of the specificity required by the present invention is critical. The present disclosure sets forth only a single immunization and spleen harvesting protocol. Claims directed to the hybridomas and monoclonal antibodies produced by the disclosed method, claims 21 and 23 respectively, have been allowed. Claims 21 and 23 are generic in nature and are not limited to the hybridomas produced according to the disclosed method which have been deposited in accordance with M.P.E.P. 608.01(p).
Claims 29 and 30 are broader than allowed claims 21 and 23 in that, in addition to encompassing the subject matter of claims 21 and 23, they also include hybridomas and monoclonal antibodies of the specified reactivity without regard to the method of their manufacture. See In re Hughes, 496 F.2d 1216, 182 USPQ 106 (CCPA 1974). It is this additional subject matter, that which is beyond the limits of claims 21 and 23, which gives rise to the present enablement issue, viz., having received protection for hybridomas and monoclonal antibodies produced according to the single disclosed method which has been established to be critical to their production, are appellants entitled to coverage for hybridomas and monoclonal antibodies beyond those disclosed and claimed in claims 21 and 23?
We conclude that appellants are not entitled to this additional coverage in view of Dr. Jochim's declaration which establishes that one of ordinary skill in the art would not be enabled to produce hybridomas and monoclonal antibodies throughout the scope of claims 29 and 30, i.e., that portion of the subject matter of these claims which extends beyond that of claims 21 and 23, without undue experimentation.
Appellants have not relied upon any evidence in response to the examiner's prima facie case of nonenablement. Rather, appellants argue that after reading the present disclosure, one of ordinary skill in this art would know exactly what to do and what to look for during this procedure and that it would be just a matter of time before identifying the desired products. However, such arguments are misplaced. It has not been questioned that the disclosed method of obtaining hybridomas and monoclonal antibodies of the required specificity is enabled. The examiner has allowed claims directed to the disclosed method, e.g., claim 20 as well as claims directed to the hybridomas and monoclonal antibodies produced according to this method. The question to be resolved in this appeal is whether generic claims 29 and 30 are enabled throughout their scope. In re Marzocchi, supra. Appellants do not point to any portion of the original disclosure of this application which would guide one of ordinary skill in the art beyond the specific protocol disclosed, or any disclosure which enables one to produce hybridomas and monoclonal antibodies beyond those already claimed in claims 21 and 23.
*4 We have considered the recent case of In re Wands, F.2d 8 USPQ2d 1400 (Fed. Cir. 1988) in reaching our decision. Wands was also concerned with an issue under 35 USC § 112, first paragraph, in regard to claims directed to monoclonal antibody technology. Keeping in mind that each case must be decided on its own facts, we find that the facts of record in this application are distinguishable from those in Wands. Here, there is no question that appellants are entitled to coverage beyond the deposited hybridomas as there was in Wands. Rather the question is what is the scope of coverage to which appellants are entitled beyond that of claims 21 and 23?
REJECTION UNDER 35 USC § 112, SECOND PARAGRAPH
The examiner is of the opinion that claim 31 does not particularly point out and distinctly claim the subject matter which appellants regard as their invention in that the preamble of claim 31 states that the claim is directed to a method of producing a hybridoma which secretes monoclonal antibody which is group specific to BTV and does not react with EHDV antigen, yet, the claim does not positively recite selecting and isolating such a hybridoma.
We will not sustain this rejection as we do not find that the metes and bounds of this claim cannot be readily ascertained by one of ordinary skill in the art. In re Moore, 58 CCPA 1042, 439 F.2d 1232, 169 USPQ 236 (1971). The examiner's concern that claim 31 does not recite selection and isolation steps is misplaced since the purpose of the claim is to define the production of the specified hybridoma, not its selection and isolation.
The examiner's rejection of claim 31 under § 112, second paragraph is reversed.
The decision of the examiner is affirmed-in-part.
37 C.F.R. 1.136(a) does not apply to the times for taking any subsequent action in connection with this appeal.
BOARD OF PATENT APPEALS AND INTERFERENCES
Irving R. Pellman
William F. Smith
APPENDED CLAIMS 20, 21, 22 AND 23
20. A method of producing a hybridoma which secrets (sic) monoclonal antibody which is group-specific to bluetongue virus (BTV) antigen and does not react with epizootic hemorrhagic disease virus (EHDV) antigen, which comprises:
(a) immunizing a mouse with BTV as follows: injecting said mouse with 2 intraperitoneal injections of 3.2 x 106 plague (sic) forming units (PFU) of BTV, given approximately 5 weeks apart; after 2 weeks, injecting said mouse with 1.6 x 106 PFU of BTV intravenously; resting said mouse 20 weeks and reinjecting it with 1.6 x 106 PFU of BTV intravenously;
*5 (b) removing the spleen from said mouse 3 days after the last injection of BTV and making a suspension of the spleen cells;
(c) fusing said spleen cells, in the presence of a fusion promotor, with mouse myeloma cells which lack hypoxanthine phosphoribosyl transferase to form hybridomas capable of producing monoclonal antibody;
(d) individually culturing said hybridoma in a medium which will support growth of only said hybridomas so that said monoclonal antibody is secreted into said culture medium;
(e) testing said antibody-containing medium for the presence of antibody which is group-specific to BTV antigen and does not react with EHDV antigen as follows:
(i) (a) reacting said antibody-containing medium with cell cultures infected with BTV serotypes 2, 10, 11, 13, and 17;
(i) (b) reacting said antibody-containing medium with cell cultures infected with EHDV serotypes 1 and 2, and
(i) (c) reacting said antibody-containing medium with uninfected cell cultures;
(ii) reacting said reacted cultures of step (i) with fluorescein isothiocyanate conjugated antimouse IgG;
(iv) selecting said antibody-containing medium in which said BTV-infected cultures show fluorescence in step (iii); said EHDV-infected cultures show no fluorescence in step (iii), and said uninfected cell cultures show no fluorescence in step (iii);
(f) cloning said hybridoma which is contained in said medium selected in step (e)(iv).
21. The hybridoma produced according to the method of claim 20.
22. The method of claim 20 which further includes:
(g) recovering said monoclonal antibody secreted by said hybridoma of step (f) by a method selected from the group consisting of (i) culturing said cloned hybridoma in a medium and recovering said antibody from said medium, and (ii) culturing said cloned hybridoma intraperitoneally in mice and harvesting malignant ascites or serum from said mice, which ascites or serum contains said antibody.
23. The monoclonal antibody produced according to the method of claim 22.