Ex Parte Keene et al

Board of Patent Appeals and Interferences

Jun 26, 2002

08862337 (B.P.A.I. Jun. 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for publication and is not binding precedent of the Board.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. 40

UNITED STATES PATENT AND TRADEMARK OFFICE
__________

BEFORE THE BOARD OF PATENT APPEALS
AND INTERFERENCES
__________

Ex parte JACK D. KEENE,
DANIEL J. KENAN, and
DONALD E. TSAI
__________

Appeal No. 2000-2269
Application No. 08/862,337
__________

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, 2, 5, 6, 8-11, 13, 14, 21, 26-34, 49, 50, 58, 59, 68-72,
78, and 79, all of the claims remaining. Claims 1 and 26 are representative and
read as follows:
1. A method of generating a nucleic acid species which is
immunologically cross-reactive with an immunogen, which
immunogen is not a nucleic acid, said method comprising:

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Application No. 08/862,337

combining an antigen binding protein which binds said
immunogen with a degenerate pool of nucleic acid species;
and then

recovering a nucleic acid species bound by said antigen
binding protein from said degenerated pool, with said nucleic
acid and said immunogen binding to the same antigen
recognition site on said antibody.

26. An isolated nucleic acid which inhibits complex formation between
an antigen binding protein and an immunogen, which immunogen is
not a nucleic acid, with said nucleic acid and said immunogen
binding to the same antigen recognition site on said antibody.

The examiner relies on the following references:
Gold et al. (Gold ‘ 163) 5,270,163 Dec. 14, 1993
Gold et al. (Gold PCT) WO 91/19813 Dec. 26, 1991
Bock et al. (Bock), “Selection of single-stranded DNA molecules that bind and
inhibit human thrombin,” Nature, Vol. 355, pp. 564-566(1992)

All of the claims stand rejected under 35 U.S.C. § 103 as obvious over
either of Gold ‘163 or Gold PCT.
All of the claims also stand rejected under 35 U.S.C. § 103 as obvious
over either of Gold ‘163 or Gold PCT, combined with Bock.
We reverse.
Background
Appellants’ specification discloses a method of making nucleic acid
mimetics of non-nucleic acid antigens, i.e., nucleic acids that are specifically
bound by an antibody that also binds a non-nucleic acid antigen. The
specification describes the process as follows:

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[S]uitable antigen binding proteins [e.g., antibodies] are . . .
combined with a degenerate pool of nucleic acid species. . . .
The pool may be formed of DNA molecules or RNA molecules,
with pools of RNA molecules currently preferred. . . . Each
nucleic acid species in the pool includes a degenerate segment
of nucleotides . . . in which each degenerate nucleotide position
is randomly assigned. . . .

Combining the anti-peptide antigen binding protein with the
degenerate pool may be facilitated by immobilizing the antigen
binding protein on a solid support and contacting the degenerate
pool . . . to the solid support. . . .

Typically, . . . the step of combining the degenerate pool with the
antigen binding protein is followed by the step of separating nucleic
acid species bound to said solid support (e.g., by washing away
any unbound nucleic acid species, then eluting nucleic acid species
bound to the solid support); then producing a pool of
complementary nucleic acids from said nucleic acid species
separated from said solid support (e.g., reverse transcribing a pool
of cDNAs from a DNA or RNA pool), then amplifying the pool of
complementary nucleic acids to produce a subset degenerate pool
of nucleic acid species. . . . This sequence of steps may be
cyclically repeated to produce numerous subset degenerate pools.

Specification, pages 10-12.
Discussion
According to Appellants, the claims stand or fall in two groups: product
claims 26-34 stand or fall together and the remaining claims (directed to
methods) stand or fall together. Appeal Brief, page 5. Therefore, we will limit our
consideration to claims 1 and 26. Claim 1 is directed to the disclosed process of
producing nucleic acid mimetics for non-nucleic acid immunogens; i.e., a process
of producing a nucleic acid that is “immunologically cross-reactive with an
immunogen,” by combining an antigen-binding protein with a degenerate pool of
nucleic acids, and recovering a nucleic acid that binds the antigen-binding protein

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at the same antigen-recognition site bound by the immunogen. Claim 26 is
directed to a nucleic acid that binds an antigen binding protein at the same
antigen recognition site as a non-nucleic acid immunogen; i.e., a nucleic acid
produced in a process such as that of claim 1.
1. The rejection over Gold
The examiner rejected the claims as obvious in view of the teachings of
either Gold ‘163 or Gold PCT.1 The examiner characterized Gold as teaching
a method for identifying nucleic acid species which interact with
targets comprising the steps: a) combining a broad class of
molecules including proteins, such as antigen binding proteins or
antibodies, [and] receptors, such as T cell receptors . . . , with a
degenerate pool of nucleic acids . . . , b) recovering a nucleic acid
bound to the target at a specific site . . . , c) amplifying selected
nucleic acids by cDNA synthesis followed by PCR and RNA
transcription. . . . Gold also teaches the interaction of selected
nucleic acids with proteins not known to bind nucleic acids . . . as
well as the use of solid supports.

Examiner’s Answer, page 4.
The examiner concluded that
[i]t would have been prima facie obvious to one having ordinary skill
in the art at the time the invention was made to utilize the method of
Gold for the identification of targets of any molecule and any
epitope. The method of Gold is not limited to the specific examples
cited in the patent, and an ordinary practitioner would have been
able to utilize the method of Gold to identify nucleic acids which
interact with any specific desired antibody, and for the selection of
nucleic acids which can compete for binding at an antibody target
site.

Examiner’s Answer, page 5.

1 Although the rejection is putatively based on either Gold reference, the examiner cited only to
Gold ‘163 when explaining the basis of the rejection. The disclosures of both Gold references
appear to be identical. Therefore, we will limit our discussion to Gold ‘163.

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Appellants argue that the nucleic acids of the present claims are different
from the “nucleic acid antibodies” disclosed by Gold, in that Gold’s nucleic acids
are defined as capable of binding “any compound of interest,” including
carbohydrates, viruses, dyes, or cofactors, whereas the nucleic acids of the
present claims bind only to the antigen recognition site of an antibody. Appeal
Brief, page 4. Appellants argue that Gold would not have suggested the instantly
claimed products and methods because “the only place in [Gold’s] lengthy
disclosure where a true antibody is mentioned as a target molecule is within the
‘laundry list’ of putative target molecules set forth at column 13, lines 54-60.” Id.,
page 5. Appellants conclude that
[t]his inclusion, in the Gold patent, of “antibodies” in a broad list of
putative target molecules does not establish that nucleic acids
binding specifically to antigen binding sites of antibodies were
contemplated by Gold, or that one skilled in the art would have had
a reasonable expectation of producing such nucleic acid ligands.

Id. Additionally, Appellants submitted rebuttal evidence in the form of a
declaration under 37 CFR § 1.132 by inventors Jack D. Keene and Daniel J.
Kenan.
“In rejecting claims under 35 U.S.C. § 103, the examiner bears the initial
burden of presenting a prima facie case of obviousness.” In re Rijckaert, 9 F.3d
1531, 1532, 28 USPQ2d 1955, 1956 (Fed. Cir. 1993). “[The Examiner] can
satisfy this burden only 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,

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972 F.2d 1260, 1265, 23 USPQ2d 1780, 1783 (Fed. Cir. 1992). “Although
couched in terms of combining teachings found in the prior art, the same inquiry
must be carried out in the context of a purported obvious ‘modification’ of the
prior art. The mere fact that the prior art may be modified in the manner
suggested by the Examiner does not make the modification obvious unless the
prior art suggested the desirability of the modification.” Id. at 1266, 23 USPQ2d
at 1783 (citations omitted).
We agree with Appellants that the examiner has not carried his burden of
showing that the claims are prima facie obvious over the prior art. We note
initially that the basis of the examiner’s rejection is somewhat difficult to discern,
because he did not address the particular limitations of any specific claim. For
example, the examiner noted that Gold differs from the claimed invention in that
Gold does not explicitly teach the collection of antibodies from
individuals, with whatever malady, for use in the assay. Gold also
does not explicitly teach specific Kd values, all possible specific
buffer conditions, or selection of nucleic acids which can compete
for binding with an antigen at an antibody target site.

Examiner’s Answer, pages 4-5. None of these limitations, however, appears in
independent claims 1 or 26.
With respect to claims 1 and 26, the examiner has not identified any
specific difference between what is claimed and what is disclosed in the prior art,
nor has he provided any reasoning as to why the difference(s) would have been
obvious to those skilled in the art. Thus, on this record, we cannot say that the
examiner has carried his burden of showing that a person skilled in the art would

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have found it obvious to modify the method taught by Gold in such a way as to
meet the limitations of claim 1, nor has he established that Gold would have
rendered obvious the product of claim 26.
The examiner’s statement that “[i]t would have been prima facie obvious to
one having ordinary skill in the art at the time the invention was made to utilize
the method of Gold for the identification of targets of any molecule and any
epitope,” Examiner’s Answer, page 5, is not sufficient. Claim 1 is not directed to
identifying the “targets of any molecule and any epitope;” it is limited to identifying
nucleic acids that bind to the antigen-recognition site of an antigen-binding
protein. Likewise, claim 26 is limited to a nucleic acid that binds to the antigen-
recognition site of an antigen-binding protein. The examiner has pointed to
nothing in the reference that would have led those skilled in the art to the
specific, claimed method or product. We conclude that the examiner has met his
burden of showing that the prior art would have motivated those skilled in the art
to modify Gold in such a way as to meet the limitations of the appealed claims.
Since we conclude that the examiner has not made out a prima facie
case, we need not address Appellants’ rebuttal evidence, presented in the Keene
and Kenan declaration. We note, however, that the examiner seemed to be
trying mainly to minimize the declaration’s evidentiary weight, rather than to
evaluate it objectively. If so, the examiner erred. “When prima facie obviousness
is established and evidence is submitted in rebuttal, the decision-maker must
start over. . . . The appealed claims must be reconsidered in the light of all the

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evidence, and the resultant finding, that the claimed invention would or would not
have been obvious, is to be made in such light. . . . [A] final finding of
obviousness may of course be reached, but such finding will rest upon evaluation
of all facts in evidence, uninfluenced by any earlier conclusion reached . . . upon
a different record.” In re Rinehart, 531 F.2d 1048, 1052, 189 USPQ 143, 147
(CCPA 1976).
2. The rejection over Gold and Bock
In addition to rejecting all of the claims over the Gold references, the
examiner also rejected all of the claims as obvious over either Gold references
combined with Bock. Again, the examiner’s rejection fails to address the
particular limitations of any specific claim, but Bock is purportedly cited “[w]ith
regard to Kd values and to identification of inhibitors.” Examiner’s Answer, page
5. The examiner characterizes Bock as “teach[ing] that selection techniques can
[be] applied using nucleic acids and identifying aptamers with affinities of 25-200
nM (abstract). Bock also teaches that these selected nucleic acid aptamers can
inhibit enzyme function . . . by binding a specific site on the protein.” Id., pages
5-6. The examiner concludes that “[i]t would have been prima facie obvious to
one having ordinary skill in the art at the time the invention was made to utilize
the method of Gold to identify aptamers as suggested by Bock since Bock states
‘The chemical nature, size and mode of isolation of aptamers may sometimes
offer advantages over existing antibody technology.’” Id., page 6.

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We reverse this rejection as well. The rejection over Gold and Bock
suffers from the same deficiencies as the rejection over Gold alone. The
examiner has pointed to nothing in the cited references that would have led one
of skill in the art to a method or product meeting the limitations of claims 1 or 26.
The examiner has not, for example, identified a difference between the teachings
of a specific prior art reference and a specific claim, then explained how the
combination of references would nonetheless have suggested the claimed
subject matter to a person skilled in the art. On this record, we cannot say that
the examiner has carried his burden of showing that the claims would have been
prima facie obvious.
Other Issues
Claims 1 and 26 both end with a reference to “said antibody.” In both
cases, “said antibody” appears to lack antecedent basis; the rest of each claim
refers to an “antigen binding protein.” In addition, claims 2 and 29 state that the
“antigen binding protein” can be either an antibody or a T cell receptor. The
examiner and Appellants may wish to consider whether claims 1 and 26 should
be amended.
In addition, we note that claims 26-34 are directed to nucleic acids defined
largely by their functional, rather than structural, properties. The Federal Circuit
has recently clarified the application of the written description requirement of 35
U.S.C. § 112, first paragraph, to nucleic acids. See University of California v. Eli
Lilly and Co., 119 F.3d 1559, 1566, 43 USPQ2d 1398, 1404 (Fed. Cir. 1997).

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The court has held that a functional definition of DNA does not satisfy the written
description requirement. See Lilly, 119 F.3d at 1566, 43 USPQ2d at 1404 (“An
adequate written description of a DNA . . . ‘requires a precise definition, such as
by structure, formula, chemical name, or physical properties,’ not a mere wish or
plan for obtaining the claimed chemical invention. Accordingly, ‘an adequate
written description of a DNA requires more than a mere statement that it is part of
the invention and reference to a potential method for isolating it; what is required
is a description of the DNA itself.’”). See also id. at 1568, 43 USPQ2d at 1406
(“A definition by function, as we have previously indicated, does not suffice to
define the genus because it is only an indication of what the gene does, rather
than what it is.”). The court recently affirmed this interpretation of the written
description requirement. See Enzo Biochem, Inc. v. Gen-Probe Inc., 285 F.3d
1013, 1022, 62 USPQ2d 1289, 1297 (Fed. Cir. 2002).
Upon return of this case, the examiner may wish to consider whether,
under the reasoning of Lilly and Enzo, claims 26-34 should be rejected for failing
to meet the written description requirement of 35 U.S.C. § 112, first paragraph.

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Summary
The examiner has not shown that the Gold references, alone or in
combination with Bock, would have rendered the instant claims prima facie
obvious. Therefore, the rejections under 35 U.S.C. § 103 are reversed.
REVERSED

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

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Application No. 08/862,337

KENNETH D. SIBLEY
P.O. BOX 37428
RALEIGH, NC 27627

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