Board of Patent Appeals and Interferences
Patent and Trademark Office (P.T.O.)
*1 EX PARTE JEFFREY K. BROWNE
Appeal No. 90-2316
September 25, 1990
Application for Patent filed February 27, 1984, Serial No. 584,132. Papova Virus Construction.
Lewis S. Gruber et al. for appellant
Supervisory Primary Examiner--Margaret Moskowitz
Examiner--Thomas M. Cunningham
Before Goldstein, Pellman and W. Smith
This is an appeal from the examiner's decision finally rejecting claims 1 through 20, all the claims in the application.
The subject matter on appeal is adequately described in our prior decision in Appeal No. 88-0499, Paper No. 14, mailed October 21, 1988, which is incorporated by reference herein. To illustrate the claims on appeal, claim 1, which is a modified form of claim 1 from the earlier appeal, is reproduced as follows:
1. A shutter vector replicative in bacterial cells and in mammalian cells supplying SV40 early gene products comprising:
a first DNA segment consisting essentially of an SV40 origin of replication, an SV40 early gene promoter, an SV40 early gene terminator, and a unique restriction site for insertion of an exogenous gene between said promoter and terminator, said promoter being between said unique site and said SV40 origin;
a third DNA segment, between said terminator and said second segment, comprising a bacterial origin of replication and a marker selectable in bacterial cells;
the shuttle vector being substantially free of SV40 late gene sequences including SV40 late gene regulatory sequences, SV40 late gene coding sequences and SV40 late gene intervening sequences.
For evidence of obviousness, the references listed below are cited by the examiner:
Seeburg 4,446,235 May 1, 1984
Levinson et al. (Levinson) 2,105,344A Mar. 23, 1983
(UK Patent Application)
Liu et al. (Liu CSH), "Expression of Hepatitis B Surface Antigen Using Lytic and Nonlytic SV40-based Vectors,"D' Gluzman (Ed.), Eukaryotic Viral Vectors, Cold Spring Harbor Laboratory, Cold Spring Harbor, NY, pp. 55-60 (1982).
Liu et al. (Liu DNA), "Direct Expression of Hepatitis B Surface Antigen in Monkey Cells from an SV40 Vector,"D' DNA, I(3), pp. 213-221 (1982).
All the claims stand rejected for being unpatentable (35 U.S.C. 103) in view of Liu DNA taken with Liu CSH, Seeburg or Levinson. At page 4 of his answer, the examiner states that Liu DNA discloses the features of the claimed shuttle vector, but does not teach a vector lacking the majority of SV40 DNA sequences. Nevertheless, the examiner reasons, Liu CSH, at page 220, second paragraph, indicates that the cloning capacity of such shuttle vector may be increased by deletion of non-essential DNA sequences, such as SV40 intron sequences. Therefore, the examiner concludes, one with ordinary skill in the subject art would have been motivated to delete other such SV40 DNA sequences based on Liu's suggestion to delete the intron sequences.
*2 Additionally, the examiner turns to the Liu CSH, Seeburg and Levinson references, each of which discloses an SV40 shuttle vector which lacks substantial amounts of SV40 DNA, including the lack of SV40 coding sequences. After pointing to the specific disclosures in each reference relating to the above, the examiner concludes that it would have been prima facie obvious to a person having ordinary skill in the art to have deleted additional SV40 DNA sequences from the Liu DNA shuttle vector to increase its cloning capacity. Therefore, the examiner holds, claims 1 through 20 would have been prima facie obvious in view of the cited prior art.
On the other hand, appellant, beginning at page 10 of the principal brief, argues that Liu DNA actually teaches away from the claimed invention by retaining both the early and late regulatory regions of the SV40 DNA and by emphasizing that the retention was intended to avoid problems that might otherwise occur. It is appellants' position that the reference does not contemplate the removal of functional DNA other than the VP-1 coding region. Appellant contends that the only other regions of the SV40 genome that Liu considers removing are the intervening sequences (introns). Although he acknowledges that the author speculates that introns may be removed to increase the capacity of the vector to accept exogenous DNA, appellant stresses that the term introns refers to non-coding regions of DNA. In support of this interpretation, appellant refers to the publication by Stryer, Biochemistry, Third Ed., Freeman and Company, NY, pp. 110-112 (1988). A copy of the publication item accompanies the reply brief as Exhibit 3.
Beginning at page 13 of the principal brief, appellant traverses the examiner's reliance upon the Seeburg reference. We are told that the patentee describes a vector in which an exogenous gene terminator is used, instead of an SV40 terminator. This is said to be contrary to the claimed invention, which involves only SV40 control elements. To illustrate the difference between the claimed invention and that of Seeburg, appellant notes that the reference vector requires the presence of a helper virus to convert it into a lytic vector that requires constructions not suggested in the reference. The foregoing is followed by a description of appellant's vector.
At page 17 of the principal brief, appellant discusses the Levinson reference. This reference is described as showing an SV40 construction in which only the VP-1 coding region is deleted, leaving intact the regulatory elements of the gene, as in Liu DNA. Appellant emphasizes that no SV40 terminators are used in the Levinson vector construction. The Levinson vector is said to be specific for the incorporation of the HBsAg gene.
Similarly, beginning at page 19 of the principal brief, appellant deals with the teachings of Liu CSH. Appellant interprets the reference as reporting the construction of a vector containing as its only SV40 DNA the SV40 origin of replication and the early and late promoters. Appellant stresses that no SV40 terminators are used in the vector construction. The reference is dismissed as failing to disclose the specific construction of the claimed shuttle vectors.
*3 In the reply brief, appellant continues his attack upon the examiner's rejection. It is argued that the cited art provides no guidance as to how to construct a vector or to perform the methods recited in the claims on appeal. To illustrate his position, appellant provides a graphic comparison of the vectors in appellant's claims in comparison with those of the references and attaches this to the reply brief as Exhibit 4.
After carefully considering the opposing arguments of appellant and of the examiner, as well as reviewing the basis for our position in deciding Appeal No. 88-0499, the earlier appeal in this application, we are convinced that a prima facie case of obviousness has not been established and that the rejection of record cannot be sustained.
The penultimate paragraph in the examiner's answer and appellant's parallel arguments at page 12 of the principal brief and page 9 of the reply brief appear to be dispositive of the appealed claims' patentability. Initially, we focus upon the examiner's statement at page 6 of the answer.
In reaching his conclusion, the examiner, at page 6 of the answer, provides the following statement:
Such complementarity between viral strains and/or host cells leading to cell lysis was well known in the art. Construction of vectors with restriction sites facilitating insertion of exogenous gene cassettes was also well-known within the art as evidenced by Levinson's insertion of growth hormone genes at the EcoR1 site (see Levinson, first page). Accordingly, Applicant's suggestion to construct a lytic SV40 vector by modular inserton of early or late SV40 genes would have been obvious to one with ordinary skill in the art given the teachings of the prior art.
In response to the foregoing, appellant, at page 9 of the reply brief, responds that:
According to the Examiner, construction of vectors with restriction sites facilitating insertion of exogenous gene cassettes was also well-known within the art, as evidenced by Levinson's insertion of growth hormone genes at the EcoR1 site (citing Levinson, first page). Accordingly, Applicant's suggestion to construct a lytic SV40 vector by modular insertion of early or late SV40 genes is asserted by the Examiner to have been obvious to one with ordinary skill in the art given the teachings of the prior art.
This final assertion of the Examiner is a non sequitur. The Examiner has asserted that, because complete lytic vectors were known, and because it was known to insert an exogenous gene into a restriction site in a vector for expressing that single gene (exemplified by the growth hormone gene), therefore it was obvious to insert a module of a whole functional region of the SV40 genome into a non-lytic vector to render it lytic.
In connection with the foregoing, we note that the examiner's reference to the first page of Levinson would seem to be in error since Levinson was not concerned with growth hormone genes. Rather, Seeburg is limited to the human growth hormone and discloses insertion of genes at the EcoRI site in Figure 4. Nevertheless, even with the correctly identified reference being substituted for Levinson, we agree with appellant that the examiner's assertion is a non sequitur. That is, the examiner's conclusion as to obviousness does not flow logically from the statement preceding it. Furthermore, as stressed by appellant, no art has been cited showing insertion of an SV40 functional region into a vector containing an exogenous gene to render it lytic. While we appreciate the examiner's apparent dilemma in giving reasons to buttress the rejection set forth under 37 C.F.R. 1.196(b), we must be honest in recognizing the truth of appellant's cogent argument raising the issue of support for the examiner's conclusion.
*4 Additionally, a feature we previously overlooked was the use of a bank of restriction endonuclease recognition sites in appellant's invention that render the vector capable of accommodating a variety of exogenous genes, as set forth at page 12 of the principal brief. Thus, although we still find it would have been prima facie obvious to remove certain material from the vector, as taught by Liu DNA, we find no hint of providing a restriction site facilitative of insertion of an SV40 late gene region, as recited in claim 1, or an early gene region, as recited in claim 7. Since these restriction sites seem to be at the heart of appellant's invention, and since the prior art is silent as to this feature, we are unable to sustain the rejection which we originally precipitated.
In light of our foregoing remarks, it is apparent that the rejection previously affirmed cannot stand. Therefore, sua sponte, for the same reasons to which we advert above, we reverse the outstanding rejection which was sustained at page 8 of our earlier opinion. Thus, there are no longer any affirmed rejections now present in this application.
For the reasons expressed above, the examiner's decision rejecting claims 1 through 20 is reversed.
BOARD OF PATENT APPEALS AND INTERFERENCES
Irving R. Pellman
William F. Smith