Ex Parte McDonnell et al

Board of Patent Appeals and Interferences

Jul 29, 2004

09266465 (B.P.A.I. Jul. 29, 2004)

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for publication and is not binding precedent of the Board.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. 33

UNITED STATES PATENT AND TRADEMARK OFFICE
__________

BEFORE THE BOARD OF PATENT APPEALS
AND INTERFERENCES
__________

Ex parte TIMOTHY J. McDONNELL, STEPHEN G. SWISHER,
BINGLIANG FANG, ELIZABETH M. BRUCKHEIMER,
MONA G. SARKISS, LIN JI, and JACK A. ROTH
__________

Appeal No. 2003-2091
Application No. 09/266,465
__________

ON BRIEF
__________

Before WILLIAM F. SMITH, SCHEINER, and GRIMES, Administrative Patent Judges.

GRIMES, Administrative Patent Judge.

DECISION ON APPEAL

This is a decision on appeal under 35 U.S.C. § 134 from the examiner’s final
rejection of claims 1-3, 6, 7, 9-13, 17-21, 23, 29-32, 34, 36, 108, 109, and 115.1 Claims
1-3 and 9 are representative and read as follows:
1. An adenoviral expression construct comprising a first nucleic acid
encoding a proapoptotic member of the Bcl-2 gene family and a non-
adenoviral first promoter inducible by a non-adenoviral inducer

1 Claims 1-115 are pending. Claims 62-67 have been allowed, and the examiner has indicated that
claims 4, 5, 8, 14, 16, 22, 24-27, 33, 35, 37, 38, 110, and 114 would be allowable if re-written to eliminate
their dependence on rejected claims. See Paper No. 21, mailed June 21, 2002, and the Examiner’s
Answer, page 4. Claims 15, 28, 39-61, 68-107, and 111-113 have been withdrawn from consideration.
See Paper No. 21.
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polypeptide wherein said first nucleic acid is under transcriptional control
of said first promoter.

2. The expression construct of claim 1, wherein said proapoptotic Bcl-2 gene
is a Bax, Bak, Bim, Bik, Bid, or Bad gene.

3. The expression construct of claim 1, further comprising a second nucleic
acid encoding a second transgene.

9. The expression construct of claim 3, wherein said second gene encodes a
protein selected from the group consisting of a tumor suppressor, a
cytokine, a receptor, inducer of apoptosis, and differentiating agents.

The examiner relies on the following references:
June et al. (June) 6,143,291 Nov. 7, 2000
Zhang et al. (Zhang) 6,194,191 Feb. 27, 2001

Lillie et al. (Lillie), “Transcription activation by the adenovirus E1a protein,” Nature,
Vol. 338, pp. 39-44 (1989)

Kaufman, “Vectors used for expression in mammalian cells,” Methods in Enzymology,
Vol. 185, pp. 487-511 (1990)

Oligino et al. (Oligino), “In vivo transgene activation from an HSV-based gene therapy
vector by GAL4:VP16,” Gene Therapy, Vol. 3, pp. 892-899 (1996)

Wang et al. (Wang), “Positive and negative regulation of gene expression in eukaryotic
cells with an inducible transcriptional regulator,” Gene Therapy, Vol. 4, pp. 432-441
(1997)

Claims 1-3, 6, 17-21, 23, 29-32, 34, and 36 stand rejected under 35 U.S.C.
§ 102(e) as anticipated by Zhang.
Claims 7, 108, 109, and 115 stand rejected under 35 U.S.C. § 103 as obvious:
• claim 7 in view of Zhang and June;
• claims 108 and 109 in view of Zhang, combined with any one of Oligino,
Wang, or Lillie, and Kaufman; and
• claim 115 in view of Zhang and Oligino.

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Claims 9-13 stand rejected under 35 U.S.C. § 112, second paragraph, as
indefinite.
We affirm the indefiniteness rejection but reverse all of the rejections over the
prior art.
Background
“Adenoviral vectors have become one of the leading vectors for gene transfer,
especially in gene therapy contexts.” Specification, page 1. “Several studies have
demonstrated the ability of adenovirus-mediated wild-type p53 [tumor suppressor]
replacement gene therapy to induce . . . apoptosis in malignant cells carrying p53 gene
mutations.” Id.
“Apoptosis, or programmed cell death, is an essential occurring process for
normal embryonic development . . . and suppressing carcinogenesis.” Id., page 2.
“[L]ittle is known of the mechanisms by which wild-type p53 induces apoptosis. It
appears that p53 induces apoptosis, at least in part, by up-regulating proapoptotic
members of the Bcl-2 family of proteins.” Id., page 1.
“Bcl-2 acts to suppress cell death triggered by a variety of stimuli. . . . [T]here is
a family of Bcl-2 cell death regulatory proteins which share in common structural and
sequence homologies. These different family members have been shown to either
possess similar functions to Bcl-2 or counteract Bcl-2 function and promote cell death.”
Id., page 2. “One such family member having Bcl-2 counteracting function is Bax.” Id.
Other proapoptotic members of the Bcl-2 family include Bak, Bad, Bid, Bik, and Harikiri.
Specification, pages 21-22.
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Discussion
Claim 1, the broadest claim on appeal, is directed to an adenoviral vector
comprising a nucleic acid encoding one of the proapoptotic members of the Bcl-2 gene
family, under the control of a non-adenoviral inducible promoter.
The examiner rejected most of the claims as either anticipated by Zhang or
obvious in view of Zhang and other prior art. The examiner rejected claims 9-13 as
indefinite.
1. Definiteness
The examiner rejected claim 9 (and claims 10-13 because of their dependence
on claim 9) as indefinite. Claim 9 depends on claim 3 which, in turn, depends on claim
1 and adds the limitation that the vector “compris[es] a second nucleic acid encoding a
second transgene.” Claim 9 adds to claim 3 the limitation that “said second gene
encodes a protein selected from the group consisting of a tumor suppressor,” etc.
The examiner concluded that claim 9 is indefinite because “there is no
antecedent basis for the term ‘said second gene.’” Paper No. 21, mailed June 21, 2002,
page 10. In response, Appellants have authorized the examiner to enter an examiner’s
amendment that would change claim 9 to recite “said second transgene”, thereby
overcoming the rejection. Appeal Brief, page 14. The examiner has indicated, as we
understand it, that he would enter such an examiner’s amendment, which would
overcome the rejection. Examiner’s Answer, page 9.
Thus, the examiner and Appellants apparently agree that claims 9-13 are
indefinite as they currently stand, but that the indefiniteness can be cured via the
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agreed-upon examiner’s amendment. We therefore affirm the rejection of claims 9-13,
in their current form, under 35 U.S.C. § 112, second paragraph.
2. Anticipation
The examiner rejected claims 1-3, 6, 17-21, 23, 29-32, 34, and 36 as anticipated
by Zhang, reasoning that Zhang “recite[s] an adenoviral expression construct . . .
comprising a nucleic acid (which can be a cDNA or genomic DNA) encoding a Bax gene
product which can be under the control of a CMV IE promoter and polyA signal. . . .
Zhang et al. therefore teaches the claimed invention.” Paper No. 16, mailed October
10, 2001. The examiner specifically cited the disclosure in Zhang’s columns 2, 25, 27-
30, and 38-39.
Appellants argue that Zhang does not describe an adenoviral expression vector
as defined by instant claim 1; i.e., one having a proapoptotic, Bcl-2-family gene under
the control of a non-adenoviral promoter. Rather, they argue, Zhang
describes a method for the production and purification of adenoviral
vectors generally. In describing such vectors, the Zhang patent lists a
great number of potential components that might be included in adenoviral
vectors amenable to the methods claimed by Zhang. There is a large
number of possible therapeutic genes listed, including p53, kinases, CDK-
inhibitors, cell adhesion molecules, numerous enzymes, over a dozen
interleukins, three dozen hormones, tumor suppressor genes, and
inducers of apoptosis – a total of nearly 100 possible genes. Within this
laundry list is found a listing of some Bcl-2 gene family members. The
[Zhang] patent also lists promoters of various sorts, including at least 17
inducible promoters and their inducing compounds.

. . . Although the [Zhang] patent does describe substitution of genes and
promoters, it does not illustrate the particular combination presently
claimed.

Appeal Brief, page 7. Thus, Appellants argue, in order to derive the claimed product
from Zhang’s disclosure,
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one must select particular species of gene from a very large genus, and
then select a particular species of promoter form a similarly large genus of
possible promoters. And even then, the claimed invention is still not
taught, as these particular elements must be combined. Forcing the
skilled artisan to make each of these selection[s] is akin to asking . . . that
person to modify the prior art. That is not anticipation.

Id., page 9.
We agree with Appellants that Zhang does not anticipate the instant claims.
“Under 35 U.S.C. § 102, every limitation of a claim must identically appear in a single
prior art reference for it to anticipate the claim.” Gechter v. Davidson, 116 F.3d 1454,
1457, 43 USPQ2d 1030, 1032 (Fed. Cir. 1997). “Every element of the claimed
invention must be literally present, arranged as in the claim.” Richardson v. Suzuki
Motor Co., Ltd., 868 F.2d 1226, 1236, 9 USPQ2d 1913, 1920 (Fed. Cir. 1989).
The examiner has not pointed to a single, specific construct disclosed by Zhang
that includes all of the limitations of the instant claims. Rather, the examiner has
pointed to the disclosure in Zhang’s columns 2, 25, 27-30, and 38-39. Those columns
describe particular promoters that can be used in adenoviral vectors (column 2, lines
34-38, and columns 27-30), specific therapeutic genes that can be included in
adenoviral vectors as cancer treatment agents (column 2, lines 46-57, and columns 23-
26), and pharmaceutical compositions (columns 38-39). Thus, as Appellants point out,
deriving the claimed adenoviral constructs from Zhang’s disclosure requires picking a
promoter from among the many promoters disclosed by Zhang, some of which are not
inducible and some of which are not non-adenoviral promoters, then picking a
therapeutic gene from among the many possible genes disclosed by Zhang, only a few
of which are proapoptotic members of the Bcl-2 gene family.
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It is true that all of the elements of the claimed product are encompassed by the
genera described in Zhang. However, when a claimed product is not specifically
described in a reference, but must be derived by choosing and combining different
elements that are separately disclosed, the proper basis for rejection (if any) is 35
U.S.C. § 103.
In response to Appellants’ argument on this point, the examiner cited guidance
from the MPEP to the effect that a claimed product can be anticipated by a prior art
reference, even if it is necessary to select portions of the reference and combine them,
so long as the classes from which the selections are made are “sufficiently limited or
well delineated.” Examiner’s Answer, page 6 (citing MPEP § 2131.02). The examiner
also relied on the MPEP for the following proposition:
If one of ordinary skill in the art is able to “at once envisage” the specific
[claimed] compound within the generic [known] chemical formula, the
compound is anticipated. One of ordinary skill in the art must be able to
draw the structural formula or write the name of each of the compounds
included in the generic formula before any of the compounds can be “at
once envisaged.”

Id. (citing In re Petering, 301 F.2d 676, 133 USPQ 275 (CCPA 1962)).
The examiner argues that this passage from the MPEP supports the rejection
because “one of ordinary skill could write out the combinations of promoters and genes;
indeed, many different combinations of the promoters and Bcl-2 transgenes disclosed in
the ‘191 patent would anticipate the claimed invention. For example, in claims reciting
any [non-adenoviral] inducible promoter . . . many of the 17 inducible promoters listed in
Table 3 . . . and several of the promoters listed in Table 2 . . . combined with any of the
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Bcl-2 family member genes . . . would anticipate claims reciting these limitations.” Id.,
pages 6-7.
The facts of this case are not analogous to those of Petering. At issue in
Petering was a claimed chemical compound that had been rejected over a prior art
patent (Karrer). See id. at 995-96, 133 USPQ at 276-77. Karrer disclosed a similar
compound having substituents at various positions that could be, but were not
necessarily, the same as those in the claimed compound. The court concluded that the
generic disclosure did not anticipate Petering’s claims: “Even though appellants’
claimed compounds are encompassed by [Karrer’s] broad generic disclosure, we do not
think this disclosure by itself describes appellants’ invention, as defined by them in any
of the appealed claims, within the meaning of 35 U.S.C. 102(b).” Id. at 1000, 133
USPQ at 279 (emphasis in original).
The court noted, however, that Karrer also described preferred substituents for
each of the variable positions. When the disclosed preferences were taken into
account, the court found that only 20 compounds were within the preferred subgenus
taught by Karrer. See id. at 1000, 133 USPQ at 279-80. The court concluded that “one
skilled in this art would, on reading the Karrer patent, at once envisage each member of
this limited class.” Id. at 1001, 133 USPQ at 280 (emphasis in original).
In the present case, by contrast, Zhang lists at least 57 promoters that could be
used in the disclosed adenoviral vectors. See Tables 2 and 3 in columns 29-30. In
addition, Appellants have asserted (and the examiner has not disputed) that Zhang
discloses nearly 100 different therapeutic agents that could be used. Thus, it would
appear that Zhang discloses a genus of adenoviral vectors comprising nearly 5700
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different members. The examiner has pointed to nothing in Zhang indicating a
preference for inducible promoters over other types of promoters, or indicating a
preference for proapoptotic members of the Bcl-2 gene family over other cancer
therapeutic genes.
Thus, the record does not indicate that one skilled in the art, on reading the
Zhang patent, would have at once envisaged each member of a limited class, as in
Petering. Zhang does not describe with specificity any product within the scope of
claim 1. The rejection for anticipation is therefore reversed.
3. Obviousness
The examiner rejected claims 7, 108, 109, and 115 as obvious in view of Zhang
combined with other prior art references. Each of these rejections, however, cited
Zhang as disclosing the basic adenoviral construct defined in claim 1, and relied on the
other references to meet limitations of the dependent claims. The examiner did not cite
any evidence or provide any reasoning to show that those skilled in the art would have
found it obvious to combine a specific promoter (or class of promoters) with a
proapoptotic member of the Bcl-2 gene family.
Since we have already concluded that Zhang does not describe an adenoviral
construct within the scope of claim 1, and the examiner has not shown that Zhang
would have made such a construct obvious, our reversal of the § 102 rejection
mandates reversal of the § 103 rejections as well.
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Summary
We reverse the rejections based on the prior art because the examiner has not
shown that the claimed adenoviral construct was described or would have been obvious
based on Zhang. We affirm the rejection for indefiniteness, with the understanding that
Appellants and the examiner have agreed on acceptable alternative language.
No time period for taking any subsequent action in connection with this appeal
may be extended under 37 CFR § 1.136(a).
AFFIRMED IN PART

WILLIAM F. SMITH )
Administrative Patent Judge )
)
)
) BOARD OF PATENT
TONI R. SCHEINER )
Administrative Patent Judge ) APPEALS AND
)
) INTERFERENCES
)
ERIC GRIMES )
Administrative Patent Judge )

EG/jlb
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