Ex Parte Lupton

Board of Patent Appeals and Interferences

Jul 26, 2002

08483941 (B.P.A.I. Jul. 26, 2002)

The opinion in support of the decision being entered today was not written
for publication and is not binding precedent of the Board.
Paper No. 41
UNITED STATES PATENT AND TRADEMARK OFFICE
__________
BEFORE THE BOARD OF PATENT APPEALS
AND INTERFERENCES
__________
Ex parte STEPHEN D. LUPTON
__________
Appeal No. 2001-0766
Application No. 08/483,941
__________
ON BRIEF
__________
Before WINTERS, ADAMS, and GREEN, Administrative Patent Judges.
WINTERS, Administrative Patent Judge.
DECISION ON APPEAL
This appeal was taken from the examiner=s decision finally rejecting claims
1-6, 11, 16, 26 and 36, which are all of the claims remaining in the application.
Representative Claim
Claim 1 is representative of the subject matter on appeal, and reads as
follows:
1. A selectable fusion gene comprising a dominant positive selectable
gene fused to and in reading frame with a negative selectable gene, wherein the
selectable fusion gene encodes a single bifunctional fusion protein which when
expressed confers a dominant positive selectable phenotype and a negative
selectable phenotype on a cellular host.
Appeal No. 2001-0766
Application No. 08/483,941
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The References
In rejecting the appealed claims under 35 U.S.C. ' 103, the examiner
relies on the following prior art references:
McKnight, AThe nucleotide sequence and transcript map of the herpes simplex
virus thymidine kinase gene,@ Nucleic Acids Research, Vol. 8, No. 24, pp. 5949-
5964 (1980)
Kaster et al.(Kaster), AAnalysis of a bacterial hygromycin B resistance gene by
transcriptional and translational fusions and by DNA sequencing,@ Nucleic Acids
Research, Vol. 11, No. 19, pp. 6895-6911 (1983)
Sugden et al. (Sugden), AA Vector That Replicates as a Plasmid and Can Be
Efficiently Selected in B-Lymphoblasts Transformed by Epstein-Barr Virus,@
Molecular and Cellular Biology, Vol. 5, No. 2, pp. 410-413 (1985)
Borrelli et al. (Borrelli), ATargeting of an inducible toxic phenotype in animal cells,@
Proceedings of the National Academy of Sciences, Vol. 85, pp. 7572-7576 (1988)
Germann et al. (Germann), AExpression of a Multidrug Resistance-Adenosine
Deaminase Fusion Gene,@ Journal of Biological Chemistry, Vol. 264, No. 3,
pp. 7418-7424 (1989)
Moolten et al. (Moolten), ACurability of Tumors Bearing Herpes Thymidine Kinase
Genes Transferred by Retroviral Vectors,@ Journal of the National Cancer Institute,
Vol. 82, No. 4, pp. 297-300 (1990)
Deliberations
Our deliberations in this matter have included evaluation and review of the
following materials:
(1) the instant specification, including claims 1-6, 11, 16, 26 and 36;
(2) appellant=s Brief on Appeal, received February 26, 1998 (certificate of
mailing February 23, 1998), and appellant=s Reply Brief, received July 27, 1998
(certificate of mailing July 23, 1998);
Appeal No. 2001-0766
Application No. 08/483,941
Page 3
(3) the Examiner=s Answer, mailed May 26, 1998;
(4) the Lupton declaration filed under the provisions of 37 CFR § 1.132,
executed November 3, 1995; and
(5) the above-cited references relied on by the examiner.
The Rejections
The appealed claims stand rejected as follows:
(1) Claims 1, 2, 6, 11, 16, 26 and 36 under 35 U.S.C. ' 103 as
unpatentable over Germann in view of Borrelli or Moolten;
(2) Claim 3 under 35 U.S.C. ' 103 as unpatentable over Germann in view
of Borrelli or Moolten, as applied to claims 1, 2, 6, 11, 16, 26 and 36, further
taken in view of Sugden; and
(3) Claims 4 and 5 under 35 U.S.C. ' 103 as unpatentable over Germann,
Borrelli or Moolten, and Sugden, as applied to claim 3, further taken in view of
Kaster and McKnight.
The examiner=s Abase rejection@ applies a combination of Germann and
Borrelli, or Germann and Moolten, to claims 1, 2, 6, 11, 16, 26 and 36.
Dependent claims 3, 4 and 5 stand rejected over the same combination of
references, with Sugden, Kaster and McKnight also applied to reach additional
limitations present in those claims. The examiner=s rationale for the Abase
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rejection@ of claims 1, 2, 6, 11, 16, 26 and 36 is set forth at pages 5-7 of the
Examiner’s Answer as follows:
Germann et al. disclose the use of a[n] in-frame chimeric
fusion gene between the genes encoding a dominant selectable
marker and a protein of interest as a simple means of selecting
for eukaryotic cells expressing the protein of interest and the
use of retroviral vectors as the means of introduction of the
chimeric genes into the cells. Germann et al. teach on page
7418, paragraph 1 the advantages of fusing the dominant
selectable gene to the gene of interest in contrast to vectors in
which the dominant selectable gene and unselectable gene of
interest are under the control of different promoters i.e.[,] the
use of a fusion gene encoding a chimeric protein ensures that
the expression of both the selected and unselected constituents
occurs in the selected cells.
Borrelli et al. and Moolten et al. each disclose that the
expression of negative selectable markers, particularly the
HSV1 thymidine kinase gene (HSV1-TK) within eukaryotic cells
(which are naturally TK+), is useful for the selective elimination
of particular cell types within a living organism. Moolten et al.
further disclose the use of the neomycin phosphotransferase
gene (NeoR) as a dominant selectable marker to select for cells
expressing the HSV1-TK gene as well[] as vectors for the
introduction of the HSV1-TK gene into cells which comprise both
a dominant selectable marker (NeoR) and the negatively
selectable gene (HSV1-TK) each under the control of a different
promoter. Cells expressing the HSV1-TK gene are selected for
by growing the transformed cells in the presence of neomycin.
Therefore, as positive selection for cells which express the
HSV1-TK gene is possible only in mutant TK- cells (whereas
both Borrelli et al. and Moolten et al. teach that one would
desire to produce cells which are naturally TK+ expressing this
gene), it would have been obvious to one of ordinary skill in the
art to construct a vector comprising a chimeric gene fusion
between the HSV1-TK gene and a dominant selectable marker
(such as NeoR) in order to be able to select for cells expressing
this useful gene within any cell type. One of ordinary skill in the
art would have been motivated to fuse the HSV1-TK gene to the
dominant selectable marker instead of using a vector similar to
that of Moolten et al. by the advantages of such a strategy
taught by Germann et al. It would have been further obvious to
transduce this vector into eukaryotic cells and to grow these
cells under the selection pressure of the dominant selectable
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gene in order to select those cells expressing the HSV1-TK
gene (i.e., the negatively selectable gene).
We disagree with that line of reasoning and, accordingly, reverse all of the
appealed ' 103 rejections.
In proceedings before the PTO, the examiner bears the burden of
establishing a prima facie case of obviousness based upon the prior art. The
examiner can satisfy this burden Aonly by showing some objective teaching in the
prior art or that knowledge generally available to one of ordinary skill in the art
would lead that individual to combine the relevant teachings of the references.@
In re Fritch, 972 F.2d 1260, 1265, 23 USPQ2d 1780, 1783 (Fed. Cir.
1992)(footnote omitted). As set forth in In re Kotzab, 217 F.3d 1365, 1369-70,
55 USPQ2d 1313, 1316 (Fed. Cir. 2000):
A critical step in analyzing the patentability of claims
pursuant to section 103(a) is casting the mind back to the
time of invention, to consider the thinking of one of
ordinary skill in the art, guided only by the prior art
references and the then-accepted wisdom in the field....
Close adherence to this methodology is especially
important in cases where the very ease with which the
invention can be understood may prompt one to fall
victim to the insidious effect of a hindsight syndrome
wherein that which only the invention taught is used
against its teacher....
Most if not all inventions arise from a combination of
old elements.... Thus, every element of a claimed
invention may often be found in the prior art.... However,
identification in the prior art of each individual part
claimed is insufficient to defeat patentability of the whole
claimed invention.... Rather, to establish obviousness
based on a combination of the elements disclosed in the
prior art, there must be some motivation, suggestion or
teaching of the desirability of making the specific
combination that was made by the applicant. (Citations
omitted.)
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Here, the motivation asserted by the examiner for combining references is
Germann=s disclosure that fusing a positive selectable gene to an unselectable
gene ensures expression of the unselectable gene. Extrapolating from that
disclosure, the examiner argues that Germann would provide incentive for fusing
a positive selectable gene to a negative selectable gene, such as disclosed in the
remaining references, to ensure expression of the negative selectable gene.
However, Moolten is the only reference relied on disclosing a vector with both a
dominant positive selectable gene and a negative selectable gene; and Moolten
does not disclose any problem expressing these genes, even though each is
under the control of a different promoter. Moolten is not faced with the problem
addressed by Germann, and Moolten=s non-fusion vector does not suffer from
the disadvantages discussed by Germann with respect to gene expression.
Germann discloses preparing fusion proteins to ensure expression of
genes which Ahave no selectable phenotype associated with their expression@ or
genes which encode Aan unselected protein@ (page 7418, column 1, first full
paragraph of text). As stated by Germann, A[t]aken together the results indicate
that the human MDR1 gene may be used as a dominant selectable marker to
introduce nonselectable genes in the form of gene fusions into human cells@
(page 7424, column 1, first full paragraph, emphasis added). In contrast, all of
the claims on appeal require a negative selectable gene. Because Germann
discloses the advantages of fusion constructs only with respect to nonselectable
genes, the artisan of ordinary skill would not have been led by Germann to
prepare a fusion protein containing a negative selectable marker of the type
disclosed in the other references. We find nothing in Germann leading the
artisan of ordinary skill to apply Germann=s fusion construct technique to negative
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selectable genes, disclosed in the secondary references and recited in the
appealed claims.
The examiner argues (Examiner=s Answer, page 11) that the claim term
Anegative selectable gene@ encompasses any gene which is not positively
selectable, and therefore encompasses the nonselectable genes disclosed by
Germann as suitable for inclusion within a fusion construct. However, that
argument is not supported by the specification=s definition of the term Anegative
selectable gene,@ or by Germann. As discussed above, Germann discloses that
fusion constructs are advantageous because they ensure expression of genes
which Ahave no selectable phenotype associated with their expression@ or genes
which encode Aan unselected protein@ (page 7418, column 1, first full paragraph
of text). In contrast, on page 18, lines 13-16, appellant=s specification defines
Anegative selectable gene@ as Aany gene which, upon being transduced into a
host cell, expresses a phenotype permitting negative selection (i.e.[,] elimination)
of stable transductants.@ Thus, in contrast to the genes disclosed in Germann,
the claimed genes, and those disclosed in the references applied in combination
with Germann, all have a selectable phenotype associated with their expression.
The examiner=s position to the contrary, notwithstanding, Germann’s disclosure
of Anonselectable genes@ does not encompass the negative selectable genes
recited in the claims, or disclosed by the references applied in combination with
Germann.
On this record, the examiner has not established adequate reason,
suggestion or motivation stemming from the prior art which would have led a
person having ordinary skill to combine Germann and Borrelli, or Germann and
Moolten, in the manner proposed. Nor do the remaining references relied on by
the examiner cure the deficiencies of the proposed combination of Germann and
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Borrelli, or Germann and Moolten. The examiner has not established that the
cited prior art would have led a person having ordinary skill to apply the fusion
techniques described by Germann to the negative selectable genes disclosed in
the remaining references. A review of appellant=s specification and claims makes
it clear that the prior art could be modified in the manner proposed by the
examiner. However, “[t]he mere fact that the prior art could be so modified would
not have made the modification obvious unless the prior art suggested the
desirability of the modification." In re Mills, 916 F.2d 680, 682, 16 USPQ2d 1430,
1432 (Fed. Cir. 1990); In re Gordon, 733 F.2d 900, 902, 221 USPQ 1125, 1127
(Fed. Cir. 1984).
For these reasons, we conclude that the examiner has not established a
prima facie case of obviousness of claims 1-6, 11, 16, 26 and 36, within the
meaning of 35 U.S.C. ' 103. We find it unnecessary to discuss the Lupton
declaration, filed under the provisions of 37 CFR ' 1.132, relied on by appellant
as rebutting any such prima facie case.
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The examiner’s decision rejecting claims 1-6, 11, 16, 26 and 36 under 35
U.S.C. ' 103 is reversed.
REVERSED
SHERMAN D. WINTERS )
Administrative Patent Judge )
)
)
DONALD E. ADAMS ) BOARD OF PATENT
Administrative Patent Judge ) APPEALS AND
)
) INTERFERENCES
)
LORA M. GREEN )
Administrative Patent Judge )
Appeal No. 2001-0766
Application No. 08/483,941
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