Ex Parte Borns

Patent Trial and Appeal Board

Mar 11, 2013

11488535 (P.T.A.B. Mar. 11, 2013)

UNITED STATES PATENT AND TRADEMARK OFFICE
__________

BEFORE THE PATENT TRIAL AND APPEAL BOARD
__________

Ex parte MICHAEL BORNS
__________

Appeal 2011-010077
Application 11/488,535
Technology Center 1600
__________

Before DONALD E. ADAMS, DEMETRA J. MILLS, and
FRANCISCO C. PRATS, Administrative Patent Judges.

PRATS, Administrative Patent Judge.

DECISION ON APPEAL
This appeal under 35 U.S.C. § 134 involves claims to chimeric DNA
polymerases. The Examiner entered a rejection for lack of written
description.
We have jurisdiction under 35 U.S.C. § 6(b). We affirm.
STATEMENT OF THE CASE
“One approach to modifying the property of a DNA polymerase is to
generate chimeric DNA polymerases in which one or more protein domains
having the requisite activity are combined with a DNA polymerase” (Spec.
1). The Specification discloses that one DNA-binding protein suitable for
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fusion with a DNA polymerase is Sso7d, which is “a small, basic
chromosomal protein from the hyperthermophilic archaeabacteria
Sulfolobus solfataricus. . . . The wild-type protein sequence is set forth in
SEQ ID NO:2” (id. at 11).
Thus, “fusion of . . . Sso7d or Sac7d from Sulfolobus sulfataricus to a
DNA polymerase, such as Pfu or Taq DNA polymerase, was shown to
greatly increase the processivity of these DNA polymerases as disclosed in
WO 01/92501 A1 and US2004/0081963 A1” (Spec. 1).
Along these lines, Appellant’s invention is directed to chimeric DNA
polymerases in which mutated forms of Sso7d or Sso7d-like proteins are
fused to a DNA polymerase domain (see id. at 11-13).
Claims 1-14, 16-22, 25, 29, and 31-33 stand rejected and appealed
(App. Br. 6).1 Claims 1, 5, 9, 13, and 18, the independent claims on appeal,
illustrate the appealed subject matter and read as follows:
1. A chimeric DNA polymerase comprising a DNA binding
domain and a polymerase domain, wherein said DNA binding domain
has seven or more mutations, one mutation being present at seven,
eight, or all nine of the following amino acid positions: 13, 16, 40, 41,
45, 55, 56, 61, and 63 of SEQ ID NO:2, or at a corresponding position
in a wild-type Sso7d-like protein, wherein the wild-type Sso7d-like
protein shows about 78% to about 98% sequence identity to the
sequence of SEQ ID NO:2.

5. A chimeric DNA polymerase comprising a DNA binding
domain and a polymerase domain, wherein said DNA binding domain
has three or more mutations, one each at amino acid positions 40, 41,
and 45 of SEQ ID NO:2, or at a corresponding position in a wild-type
Sso7d-like protein, wherein the wild-type Sso7d-like protein shows

1 Appeal Brief entered November 22, 2010. Appellant presented a corrected
copy of the appealed claims in a paper entered December 28, 2010.
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about 78% to about 98% sequence identity to the sequence of SEQ ID
NO:2.

9. A chimeric DNA polymerase comprising a DNA binding
domain and a polymerase domain, wherein said DNA binding domain
has six or more mutations, one each at amino acid positions 40, 41,
45, 55, 61, and 63 of SEQ ID NO:2, or at corresponding positions in a
wild-type Sso7d-like protein, wherein the wild-type Sso7d-like
protein shows about 78% to about 98% sequence identity to the
sequence of SEQ 1D NO:2.

13. A chimeric DNA polymerase comprising a DNA binding
domain and a polymerase domain, wherein said DNA binding domain
has mutations at amino acid positions 13, 16, 40, 45, 55, 56, and 63 of
SEQ ID NO:2, or at corresponding positions in a wild-type Sso7d-like
protein, wherein the wild-type Sso7d-like protein shows about 78% to
about 98% sequence identity to the sequence of SEQ 1D NO:2.

18. A chimeric DNA polymerase comprising a DNA binding
domain and a polymerase domain, wherein said DNA binding domain
has mutations at amino acid positions 13, 16, 40, 41, 45, 55, 56, 61
and 63 of SEQ ID NO:2, or at corresponding positions in wild-type
Sso7d-like protein, wherein the wild-type Sso7d-like protein shows
about 78% to about 98% sequence identity to the sequence of SEQ ID
NO:2.

The sole rejection before us for review is the Examiner’s rejection of
claims 1-14, 16-22, 25, 29, and 31-33 under 35 U.S.C. § 112, first
paragraph, as failing to comply with the written description requirement.

DISCUSSION
The Examiner initially noted that, while the claims recite mutations at
specific locations of the Sso7d amino acid sequence, the mutations “include
but are not limited to one or more point mutations, N- and/or C-truncations,
internal deletion or insertion . . . or any additional type of post-translational
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modification at these referred to amino acid positions” (Ans. 4 (citing Spec.
22, 24)). The Examiner reasoned, therefore, that the claimed DNA
polymerases “have no required structure for either the DNA binding domain
or the polymerase domain” (id.).
While contending that the genus of chimeric DNA polymerases
encompassed by the claims is thus limited only “by the number and position
of mutations of the DNA binding domain relative to SEQ ID NO:2[,]” the
Examiner also noted the claims’ separate recitation of mutations not only
“relative to SEQ ID NO:2, but also those mutation positions which are a
corresponding mutation in an Sso-7d-like protein” (id.).
In contrast to this claim breadth, the Examiner found that the
Specification “only provides the representative species of [a] chimeric DNA
polymerase comprising the amino acid sequence of SEQ ID NO: 20,
encompassed by these claims. There is no disclosure of any particular
structure to function/activity relationship in the disclosed species” (id. at 5).
The Examiner also found that the Specification “fails to describe
additional representative species of these enzymes by any identifying
structural characteristics or properties other than DNA polymerase activity
and corresponding mutation positions recited in claim 1, for which no
predictability of structure is apparent” (id). The Examiner further reasoned
that given the “lack of additional representative species as encompassed by
the claims, Appellant[] ha[s] failed to sufficiently describe the claimed
invention, in such full, clear, concise, and exact terms that a skilled artisan
would recognize Appellant[] w[as] in possession of the claimed invention”
(id.).
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Appellant contends that a sufficient correlation between the structure
and function of the claimed polymerases is provided by the fact that, in
addition to being known in the art, the Specification provides the amino acid
sequence of the Sso7d protein as well as a number of examples of Sso7d-like
proteins, and the claims recite the specific positions within that sequence of
the mutations required by the claims (see App. Br. 15). Thus, Appellant
urges, a skilled artisan
could readily identify each of the mutated residues in the
known sequences of the DNA binding proteins encompassed by
the claims with reference to SEQ ID NO:2 and Sso7d-like
proteins because the recited mutated residues are specifically
disclosed in SEQ ID NO:2 and are easily identifiable from the
alignment presented in Figure 1.

(Id. at 16; see also id. at 25, 27, 29, 31.) In other words, Appellant argues,
“the claims specifically recite the mutant polymerases by way of defined
alterations to the amino acid sequences of known DNA binding proteins (i.e.,
by complete structural information) described in the specification” (id. at
16).
Appellant further contends that, although the claims encompass
chimeric polymerases with any number of mutations in addition to those
specifically recited, that fact does not demonstrate that the claims lack
descriptive support (id. at 17 (citing Ex parte Anderson, Appeal No. 2005-
0908); see also id. at 25, 27, 29, 31-32).
In particular, Appellant urges, SEQ ID NO:2 provides “a starting
point for one of skill in the art to identify corresponding residues in other
DNA polymerases having homologous structures to SEQ ID NO:2” (App.
Br. 18). Similarly, Appellant argues, the six wild-type Sso7d-like proteins
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provided in Appellant’s disclosure would allow a skilled artisan to “readily
identify all chimeric DNA polymerases covered by the claims” (id.).
As stated in In re Oetiker, 977 F.2d 1443, 1445 (Fed. Cir. 1992):
[T]he examiner bears the initial burden . . . of presenting a
prima facie case of unpatentability. . . .
After evidence or argument is submitted by the applicant
in response, patentability is determined on the totality of the
record, by a preponderance of evidence with due consideration
to persuasiveness of argument.

Appellant’s arguments do not persuade us that a preponderance of the
evidence fails to support the Examiner’s position.
As to the Board’s previous decision in Ex parte Anderson, we note the
decision’s express statement that it is not binding precedent (see App. Br.,
Appendix 4).
Moreover, as our reviewing court has more recently pointed out, the
written description requirement “ensures that when a patent claims a genus
by its function or result, the specification recites sufficient materials to
accomplish that function - a problem that is particularly acute in the
biological arts.” Ariad Pharms., Inc. v. Eli Lilly and Co., 598 F.3d 1336,
1352-53 (Fed. Cir. 2010) (en banc).
Thus, a “sufficient description of a genus . . . requires the disclosure
of either a representative number of species falling within the scope of the
genus or structural features common to the members of the genus so that one
of skill in the art can ‘visualize or recognize’ the members of the genus.” Id.
at 1350 (quoting Regents of the University of California v. Eli Lilly & Co.,
119 F.3d 1559, 1568-69 (Fed. Cir. 1997)).
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Accordingly, “merely drawing a fence around the outer limits of a
purported genus is not an adequate substitute for describing a variety of
materials constituting the genus and showing that one has invented a genus
and not just a species.” Id.
Nonetheless, “the written description requirement does not demand
either examples or an actual reduction to practice; a constructive reduction to
practice that in a definite way identifies the claimed invention can satisfy the
written description requirement.” Id. at 1352 (citing Falkner v. Inglis, 448
F.3d at 1366-67 (Fed. Cir. 2006)).
Specifically, the Federal Circuit has “set forth a number of factors for
evaluating the adequacy of the disclosure [supporting generic claims],
including ‘the existing knowledge in the particular field, the extent and
content of the prior art, the maturity of the science or technology, [and] the
predictability of the aspect at issue.’” Id. at 1351 (quoting Capon v. Eshhar,
418 F.3d 1349, 1359 (Fed. Cir. 2005)).
Here, the genera encompassed by Appellant’s claims are relatively
broad, as the claims have very little limitation as to structure. For example,
contrary to Appellant’s seeming suggestion, claim 1 does not recite a
chimeric DNA polymerase having a DNA binding domain with the amino
acid sequence of SEQ ID NO:2, or having 78% to about 98% sequence
identity to the sequence of SEQ ID NO:2, with at least seven mutations at
the positions recited in the claim.
Rather, because of its concededly open language (see App. Br. 17, n.
2), claim 1 encompasses any DNA polymerase that also has a DNA binding
domain, as long as the binding domain has something other than the amino
acids naturally present at positions 13, 16, 40, 41, 45, 55, 56, 61, and 63 of
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SEQ ID NO:2, or at the corresponding positions in a wild-type Sso7d-like
protein that has about 78% to about 98% sequence identity to the sequence
of SEQ ID NO:2. While they recite slightly different required mutations,
independent claims 5, 9, 13, and 18, reproduced above, are similarly broad
as to the structures encompassed.
Moreover, rather than being simple one-for-one amino acid
substitutions, the many changes to SEQ ID NO:2 or its similar sequences
can include N-terminal, internal, or C-terminal truncations (see Spec. 25).
Thus, we detect no error in the Examiner’s conclusion, stated in the Final
Rejection, that claims 1, 5, 9, 13, and 18, encompass structures which “may
be ‘mutated’ an unlimited number of times such that [they] in no way
resemble[] anything that would ever be construed as being associated with
SEQ ID NO:2” (Final Rejection 4).
Turning to the Specification, in contrast to the wide variation in
structures encompassed by the claims, the only expressly described
functional chimeric DNA polymerases having mutated DNA binding
domains are constructs having the Sso7d protein as the binding domain, with
specific single amino acid substitutions at specific positions in the protein’s
sequence (see Spec. 12-13, 39-42; see also Fig. 2). While a number of
amino acid substitutions were tested, the “results indicated that only a
limited number of amino acids could be changed without causing a loss of
Sso7d functionality in the DNA polymerase chimera” (Spec. 41).
Other than those specific single amino acid substitutions in the Sso7d
sequence, however, Appellant does not direct us to, nor do we see, any
specific guidance correlating protein sequence, i.e. structure, to enzymatic
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function. To the contrary, the Specification suggests that modifying these
proteins is unpredictable:
It was observed that many amino acids that vary between the
Sso7d-like polypeptides could not be changed without
negatively effecting the Sso7d-chimeric DNA polymerases. In
addition, some of the amino acids which did not vary between
the Sso7d like proteins could be changed without causing a loss
of Sso7d-chimeric DNA polymerase functionality.

(Id. at 12; see also id. at 42 (“Amino acids L and A are structurally very
similar to I and yet all changes resulted in a functionally deficient chimera
when compared to the wild-type construct.”)).
Thus, given the unpredictability in modifying these proteins, and
given the fact that each of independent claims 1, 5, 9, 13, and 18
encompasses a broad genus of chimeric DNA polymerases that includes
significantly modified molecules which need not have any particular
similarity with the Sso7d protein (SEQ ID NO:2) or an Sso7d-like protein,
and further given the fact that the Specification describes only certain
specific amino acid substitutions to the Sso7d sequence which provide a
functional DNA polymerase, Appellant’s arguments do not persuade us that
the Examiner erred in finding that the Specification failed to adequately
describe the full scope of the subject matter recited in claims 1, 5, 9, 13, and
18. We therefore affirm the Examiner’s rejection of those claims, and their
dependents, for failing to comply with the written description requirement of
35 U.S.C. § 112, first paragraph.

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Application 11/488,535

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TIME PERIOD
No time period for taking any subsequent action in connection with
this appeal may be extended under 37 C.F.R. § 1.136(a).

AFFIRMED

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