Ex Parte Wolber et al

Board of Patent Appeals and Interferences

Apr 24, 2009

11008603 (B.P.A.I. Apr. 24, 2009)

UNITED STATES PATENT AND TRADEMARK OFFICE
____________________

BEFORE THE BOARD OF PATENT APPEALS
AND INTERFERENCES
____________________

Ex parte PAUL K. WOLBER,
ROBERT H. KINCAID, DOUGLAS AMORESE,
DIANE ILSLEY-TYREE, ANDREW S. ATWELL,
MEL N. KRONICK, and
ERIC M. LE PROUST,
Appellants
____________________

Appeal 2009-2252
Application 11/008,6031
Technology Center 1600
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Decided:2 April 24, 2009
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Before CAROL A. SPIEGEL, TONI R. SCHEINER, and
MELANIE L. MC COLLUM, Administrative Patent Judges.

SPIEGEL, Administrative Patent Judge.

DECISION ON APPEAL

1 Application 11/008,603, ("the 603 application"), Chemical Arrays and
Methods of Using the Same, filed 8 December 2004, is a continuation-in-part
of application 09/628,472, filed 31 July 2000. The real party in interest is
AGILENT TECHNOLOGIES, INC. (Appellants' Brief filed 30 May 2008
("App. Br.") at 3).
2 The two month time period for filing an appeal or commencing a civil
action, as recited in 37 C.F.R. § 1.304, begins to run from the decided date
shown on this page of the decision. The time period does not run from the
Mail Date (paper delivery) or Notification Date (electronic delivery).
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Application 11/008,603

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I. Statement of the Case
Appellants appeal under 35 U.S.C. § 134 from an Examiner's final
rejection of claims 1-9. Claims 12-18, the only other pending claims, stand
withdrawn from consideration (App. Br. 3; Ans.3 2). We have jurisdiction
under 35 U.S.C. § 134. We REVERSE.
The subject matter on appeal is directed to a method comprising
generating a mixture of desired nucleic acid products and contacting the
mixture with an addressable array of nucleic acid probes. Claim 1 is
illustrative and reads (App. Br. 12):
1. A method comprising:
(a) subjecting an array comprising a
plurality of features, each comprising nucleic acids
immobilized on a surface of a solid support via a
cleavable domain having a cleavable region, to
conditions sufficient to generate a solution phase
composition of nucleic acids;
(b) contacting said solution phase
composition of nucleic acids with one or more
reactants to produce a mixture of product nucleic
acids; and
(c) contacting said product nucleic acids
with an addressable array of probe nucleic acids.

The Examiner has rejected claims 1-9 under 35 U.S.C. § 103(a) as
unpatentable over Lipshutz4 and Nallur5 (Ans. 3).

3 Examiner's Answer mailed 21 August 2008 ("Ans.").
4 U.S. Patent 6,013,440, Nucleic Acid Affinity Columns, issued 11 January
2000, to Lipshutz et al. ("Lipshutz").
5 U.S. Patent 6,692,915 B1, Sequencing a Polynucleotide on a Generic Chip,
issued 17 February 2004, based on application 09/619,812, filed 20 July
2000, to Girish N. Nallur ("Nallur").
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According to the Examiner, Lipshutz discloses steps (a) and (b) of
claim 1, but fails to disclose immobilizing the product nucleic acids of step
(b) by capturing them with an array-addressed nucleic acids (Ans. 3-4). The
Examiner found that Lipshutz discloses not only two other methods of
immobilizing the product nucleic acids onto an affinity matrix, but also that
immobilization techniques are known in the art (Ans. 4). According to the
Examiner, Nallur discloses capturing a mixture of product nucleic acids with
an addressable array of nucleic acids for high throughput sequence
identification of novel sequences without cloning or other sequencing
techniques (Ans. 5). The Examiner concluded that it would have been
obvious to use an addressable array as disclosed by Nallur to immobilize the
product nucleic acids to the affinity matrix of Lipshutz for the expected
benefits of high throughput identification of novel sequences without
cloning or other sequencing techniques, as taught by Nallur (Ans. 5).
Appellants essentially argue that since Lipshutz relies on
hybridization between the nucleic acids immobilized on the affinity matrix
and target nucleic acids in a sample to specifically bind and remove the
target nucleic acids from the sample, immobilizing the product nucleic acids
by hybridization to an addressable array of complementary nucleic acids
would render the affinity matrix unsuitable for use (App. Br. 7-8; Reply Br.6
3-4). In other words, if the "capture" product nucleic acids were attached to
the affinity matrix of Lipshutz via hybridization to an array of
complementary nucleic acids, the complementary nucleic acids in the array
would compete with the complementary target nucleic acids in the sample

6 Appellants' Reply Brief filed 7 October 2008 ("Reply Br.").
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for hybridization to the capture product nucleic acids, thereby rendering the
affinity matrix unsuitable for its intended use.
Thus, the issue is whether Appellants have shown that the Examiner's
proposed modification of the affinity matrix of Lipshutz by Nallur would
render the affinity matrix of Lipshutz unsuitable for its intended use.
II. Findings of Fact ("FF")
[1] Lipshutz discloses a method comprising
(a) immobilizing an array of template nucleic acids on a substrate
via cleavable linkers, the template nucleic acids having different,
known sequences which preferably encode "capture probes" which
can be incorporated into an affinity matrix;
(b) cleaving the linker to release the template nucleic acids into
solution where they are amplified, preferably by a PCR
(polymerase chain reaction), to provide a population of capture
probes; and
(c) attaching the capture probes to a solid matrix to produce an
affinity matrix (Lipshutz 2:16-26 and 55-62; 10:39-54).
[2] According to Lipshutz, sample is contacted with the affinity
matrix such that the incorporated/immobilized capture probe
specifically hybridizes to and thereby captures its complementary
target nucleic acid (Lipshutz 7:34-38; 26:3-6).
[3] Further according to Lipshutz, methods of attaching
oligonucleotides to solid supports are well known in the art and the
amplified capture probes may be attached to the matrix via
covalent coupling or streptavidin-biotin coupling (Lipshutz 23:52-
63).
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[4] Nallur discloses a method of analyzing a target sequence in a
sample, wherein the target sequence is at least partially single
stranded and contains a region of recognizable sequence adjacent
to the single stranded terminus (Nallur 2:33-42).
[5] The method of Nallur comprises amplifying the target sequence
and hybridizing the amplified products with an addressable array
of capture probes, thereby analyzing the sample (Nallur 2:43-67;
3:52-53).
[6] Nallur exemplifies preparing an addressable array by depositing
each capture probe onto a known location on a derivatized glass
slide to promote covalent association of probes to the glass
surfaces (Nallur 34:51-35:32).
III. Discussion
A. Legal principles
"[R]ejections on obviousness grounds cannot be sustained by mere
conclusory statements; instead, there must be some articulated reasoning
with some rational underpinning to support the legal conclusion of
obviousness." In re Kahn, 441 F.3d 977, 988 (Fed. Cir. 2006). Where a
proposed modification would render the prior art invention being modified
unsatisfactory for its intended purpose, the proposed modification would not
have been obvious. See Tec Air Inc. v. Denso Mfg. Michigan Inc., 192 F.3d
1353, 1360 (Fed. Cir. 1999); In re Gordon, 733 F.2d 900, 902 (Fed. Cir.
1984).
B. Analysis
A solid phase affinity matrix removes a target moiety from a sample
by specifically binding the target moiety to a capture moiety immobilized on
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the solid phase matrix, e.g., by specifically hybridizing one nucleic acid
sequence to its complementary nucleic acid sequence. Lipshutz is directed
to a method of making an affinity matrix which comprises attaching a
capture moiety, i.e., capture probes, to an affinity matrix (FF 1). The affinity
matrix of Lipshutz specifically hybridizes to and thereby captures its
complementary target nucleic acid (FF 2). According to Lipshutz, the
capture probes are attached to matrix using covalent coupling, streptavidin-
biotin coupling, or other known attachment techniques (FF 3). It stands to
reason that if the capture probes were removed from the affinity matrix, the
matrix would lose its affinity for target.
The Examiner proposes attaching the capture probes of Lipshutz to an
addressable array of complementary probes via hybridization as taught by
Nallur (FF 5) (Ans. 4-5). Appellants argue that the affinity matrix of
Lipshutz requires the capture probes to be covalently attached to the matrix
or else the affinity matrix will be unsuitable for its intended use of
specifically hybridizing to and removing target from a sample (App. Br. 7-8;
Reply Br. 3-4). In other words, the capture moieties of Lipshutz can either
hybridize to the array of Nallur or to the target moieties of the sample; and,
since Lipshutz teaches that its affinity matrices "'rely on hybridization
between the nucleic acids comprising the affinity matrix and any target
nucleic acids'", the Examiner's proposed modification would render the
affinity matrix unsuitable for its intended use (Reply Br. 3, quoting Lipshutz
24:31-35 (emphasis added)).
The Examiner repeatedly responds that Lipshutz does not require the
capture probes to the covalently linked to the affinity matrix not only
because covalent linkage is taught as an alternative attachment means, but
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also because a biotinylated oligonucleotide and a streptavidin coated support
linkage is not a covalent linkage (Ans. 6-8; see also FF 3).
The Examiner is technically correct that linking a biotinylated
oligonucleotide to a streptavidin coated support does not form a covalent
linkage. However, the Examiner's response fails to address substantively
Appellants' essential argument that the capture probes of Lipshutz will either
hybridize to the array of Nallur or to the target moieties of the sample and,
thus, render the affinity matrix unsuitable for its intended use. Notably, both
Lipshutz and Nallur teach and/or suggest immobilizing the probes to solid
matrices in a such manner that the probes will not be released from the solid
matrices as a result of the hybridization reaction which captures target (FF 3
(covalent or biotin-streptavidin coupling, e.g.) and 6 (covalent coupling)).
Thus, while Lipshutz does not require the capture probes to be covalently
linked to the affinity matrix, the Examiner has not explained why one of
ordinary skill in the art would have attached the capture probes of Lipshutz
to its affinity matrix with a technique which allows for the capture probes to
be released from the affinity matrix during use due to competitive
hybridization between the complementary nucleic acids in the matrix array
and the complementary nucleic acids in the sample.
Therefore, based on the foregoing, we are constrained to reverse the
rejection of claims 1-9 under § 103 over Lipshutz and Nallur.
C. Conclusion
Appellants have shown that the Examiner's proposed modification of
the affinity matrix of Lipshutz by Nallur would render the affinity matrix of
Lipshutz unsuitable for its intended use.

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IV. Order
Upon consideration of the record, and for the reasons given, it is
ORDERED that the decision of the Examiner to reject claims 1-9
under 35 U.S.C. § 103(a) as unpatentable over Lipshutz and Nallur is
REVERSED.
REVERSED

MAT

AGILENT TECHNOLOGIES, INC.
Intellectual Property Administration, Legal Dept.
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