Ex Parte Lemmens

Board of Patent Appeals and Interferences

Aug 10, 2009

10504884 (B.P.A.I. Aug. 10, 2009)

UNITED STATES PATENT AND TRADEMARK OFFICE
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BEFORE THE BOARD OF PATENT APPEALS
AND INTERFERENCES
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Ex parte RAF LEMMENS
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Appeal 2009-004920
Application 10/504,884
Technology Center 1600
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Decided: August 10, 2009
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Before ERIC GRIMES, RICHARD M. LEBOVITZ, and STEPHEN
WALSH, Administrative Patent Judges.

WALSH, Administrative Patent Judge.

DECISION ON APPEAL
This is an appeal under 35 U.S.C. § 134(a) involving claims to a
method of separating nucleic acid molecules from contaminants. The Patent
Examiner rejected the claims as obvious. We have jurisdiction under
35 U.S.C. § 6(b). We reverse.
Appeal 2009-004920
Application 10/504,884

STATEMENT OF THE CASE
The invention relates to a method of separating nucleic acid molecules
from other components in a solution. (Spec. 1, ¶ 1.) According to the
Specification, “[t]he method utilises [sic] aromatic thioether ligands for
adsorption of the nucleic acid molecules and provides a novel scheme of
desorbing the adsorbed molecules . . . .” (Id.) Claims 1-10, which are all the
pending claims, are on appeal. Claim 1 is representative and reads as
follows:
1. A method of separating nucleic acid molecules from contaminants in a
solution and isolating one or more desired nucleic acid molecules,
which method comprises the following steps

(a) providing an aqueous adsorption solution, which includes
nucleic acids and a salt that forms lyotropic ions when
dissolved;
(b) passing said solution over a matrix to adsorb the nucleic acids
onto the matrix, said matrix including an aromatic ring moiety
and at least one thioether moiety;
(c) passing an aqueous eluent over said matrix to desorb the
nucleic acid molecules therefrom, which eluent includes a salt
that forms lyotropic ions and a gradient of increasing ionic
strength originating from an increasing concentration of a salt
that forms less lyotropic ions when dissolved than the ones
present in said aqueous adsorption solution; and
(d) isolating a fraction comprising the desired nucleic acid
molecules.

The Examiner rejected all the claims under 35 U.S.C. § 103(a) as
obvious over the combined teachings of Hansen,1 Porath2 and Prazares.3

1 WO 92/16292, by Lihme et al., published Oct. 1, 1992. The Examiner and
Appellant refer to this document using the second inventor’s name,
“Hansen.” We will do the same to avoid more confusion.
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Appeal 2009-004920
Application 10/504,884

OBVIOUSNESS
The Issue
The Examiner found that Hansen taught a method of separating
nucleic acids by adsorption on a matrix as claimed and taught that “ionic
strength can be varied during elution.” (Ans. 3.) However, Hansen’s
examples concerned proteins; Hansen did not exemplify gradient elution or
nucleic acid separation. (Id.) The Examiner’s position is that it was “well
within the purview of one of ordinary skill in the art to use gradient elution
in[ ]order to optimize the separation process[,] as instantly claimed.” (Id. at
4.) The Examiner reasons that a person of ordinary skill in the art “knows
that the use of decreasing [ionic strength] used for proteins need not
necessarily work for nucleic acids and would want to use salt solution of
increasing ionic strength (suggested by Hansen et al.) as a logical
alternative.” (Id. at 7.)
Appellant contends that “[e]lution, as described and examplified [sic]
by Hansen ‘292, is obtained by decreasing the salt concentration.” (App. Br.
4.) Appellant disputes that Hansen provided information that would
encourage using an elution solution similar to the claimed method. (Id.)
Appellant agrees that ionic strength was varied in Hansen’s elution step,
“but the salt concentration is always reduced, and the lyotropic salt removed
2 U.S. Patent No. 4,696,980, issued to Jerker Porath, Sep. 29, 1987.
3 M.M. Diogo et al., Separation and Analysis of Plasmid Denatured Forms
Using Hydrophobic Interaction Chromatography, 275 ANAL. BIOCHEM.
122-24 (1999). The Examiner and Appellant refer to this document using
the name “Prazeres,” the last of four co-authors. We will do the same to
avoid more confusion.

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Appeal 2009-004920
Application 10/504,884

or significantly reduced.” (Id.) Further, Appellant argues that Porath taught
elution in a sulfate-free buffer, and Prazeres related to hydrophobic
interaction chromatography “which by definition elutes using a decreased
salt concentration.” (Id. at 5.)
The issue in this appeal is whether the evidence supports the
Examiner’s finding that Hansen suggested elution with increasing ionic
strength.

Findings of Fact
1. Hansen described a thiophilic adsorption matrix that comprised a
thioether moiety and an aromatic ring moiety. (Abstract.)
2. Hansen described an adsorbing step that used a lyotropic salt solution,
followed by an eluting step at reduced salt concentration. (1:15-21.)
3. Hansen’s matrix could be used to separate nucleic acids. (2:12-13.)
4. Hansen explained that using a high ionic strength lyotropic solution
followed by elution with a low ionic strength lyotropic buffer solution
“can result in a considerably greater capacity than the one achievable
by known methods.” (11:3-34.)

Principles of Law
When determining whether a claim is obvious, an Examiner must
make “a searching comparison of the claimed invention – including all its
limitations – with the teaching of the prior art.” In re Ochiai, 71 F.3d 1565,
1572 (Fed. Cir. 1995). A rejection for obviousness must include “articulated
reasoning with some rational underpinning to support the legal conclusion.”
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Appeal 2009-004920
Application 10/504,884

KSR Int’l Co. v. Teleflex Inc., 550 U.S. 398, 418 (2007), quoting In re Kahn,
441 F.3d 977, 988 (Fed. Cir. 2006).

Analysis
Hansen described an adsorption method which used a decreased ionic
strength solution to elute a protein of interest from the adsorption matrix.
(FF2.) Hansen disclosed that loading the matrix with a high ionic strength
adsorption solution and eluting with a low ionic strength eluent resulted in
greater capacity. (FF4.) Hansen’s eluents all had lower ionic strength than
the adsorption solution. The Examiner interpreted Hansen’s disclosure to
mean that ionic strength can be varied during elution. We agree, but we find
that all of Hansen’s variations were shifts to lower ionic strength, the
opposite of what Appellant claims.
Although Hansen taught that nucleic acids could be separated on the
same matrix (FF3), Hansen did not give instructions for adsorbing or eluting
solutions to be used that were any different from the instructions for protein
separation. The Examiner has not pointed to a statement in Hansen that
suggested using an eluent with increased ionic strength. Although the
Examiner found that Hansen suggested increasing ionic strength, the
Examiner did not cite to an explicit disclosure in Hansen, and we do not see
the explicit suggestion in Hansen.
The Examiner reasoned that eluting nucleic acids with an increased
ionic strength was a “logical alternative” to Hansen’s step of eluting proteins
with a decreased ionic strength. (Ans. 7.) The Examiner has not provided
evidence that a person of ordinary skill in the art at the time of the invention
would have shared that reasoning. The Examiner’s citations to Porath and
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Prazeres do not refer to the missing gradient teaching, and do not show that
an elution gradient of increasing ionic strength to elute a nucleic acid from
Hansen’s matrix would have been obvious.

CONCLUSIONS OF LAW
The evidence does not support the Examiner’s finding that Hansen
suggested elution with increasing ionic strength. We conclude that a prima
facie case of obviousness was not established.

SUMMARY
We reverse the rejection of claims 1-10 under 35 U.S.C. § 103(a) as
obvious over the combined teachings of Hansen, Porath and Prazares.

REVERSED

cdc

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