Ex Parte Demmer et al

Patent Trial and Appeal Board

Oct 31, 2012

11436861 (P.T.A.B. Oct. 31, 2012)

UNITED STATES PATENT AND TRADEMARK OFFICE
UNITED STATES DEPARTMENT OF COMMERCE
United States Patent and Trademark Office
Address: COMMISSIONER FOR PATENTS
P.O. Box 1450
Alexandria, Virginia 22313-1450
www.uspto.gov
APPLICATION NO. FILING DATE FIRST NAMED INVENTOR ATTORNEY DOCKET NO. CONFIRMATION NO.
11/436,861 05/17/2006 Wolfgang Demmer 3568.0103 8876
152 7590 10/31/2012
CHERNOFF, VILHAUER, MCCLUNG & STENZEL, LLP
601 SW Second Avenue
Suite 1600
PORTLAND, OR 97204-3157
EXAMINER
FERNANDEZ, SUSAN EMILY
ART UNIT PAPER NUMBER
1651
MAIL DATE DELIVERY MODE
10/31/2012 PAPER
Please find below and/or attached an Office communication concerning this application or proceeding.
The time period for reply, if any, is set in the attached communication.
PTOL-90A (Rev. 04/07)

UNITED STATES PATENT AND TRADEMARK OFFICE
__________

BEFORE THE PATENT TRIAL AND APPEAL BOARD
__________

Ex parte WOLFGANG DEMMER, DIETMAR NUSSBAUMER,
and HANS-HEINRICH HÖRL
__________

Appeal 2011-0104371
Application 11/436,861
Technology Center 1600
__________

Before TONI R. SCHEINER, STEPHEN WALSH, and ERICA A. FRANKLIN,
Administrative Patent Judges.

SCHEINER, Administrative Patent Judge.

DECISION ON APPEAL
This is an appeal under 35 U.S.C. § 134 from the final rejection of
claims 1 and 10, directed to a membrane for removing proteases from a
fluid. The claims have been rejected as obvious. We have jurisdiction under
35 U.S.C. § 6(b).
We reverse.

1 This appeal is related to Appeal No. 2011-010030 (in Application No.
10/516,405). We have considered the two appeals together.

Appeal 2011-010437
Application 11/436,861

2
STATEMENT OF THE CASE
Claims 1 and 10 are pending and on appeal. Claims 2-9 have been
canceled (App. Br. 2).
Claim 1 is representative of the subject matter on appeal:
1. A membrane for removing proteases from a fluid consisting
essentially of an epoxy-functionalized microporous membrane containing
epoxy groups chemically coupled to at least one protease inhibitor selected
from the group consisting of pepstatin, bestatin, diprotin, antipain,
chymostatin, leupeptin, E64, TLCK and p-aminobenzamidine, wherein said
at least one protease inhibitor is coupled by a chemical bond to said
membrane via said epoxy groups.
The Examiner relies on the following evidence:
JERRY MARCH, ADVANCED ORGANIC CHEMISTRY 369 (3d ed. 1985).
P. Langlotz & K.H. Kroner, Surface-modified membranes as a matrix for
protein purification, 591 JOURNAL OF CHROMATOGRAPHY 107-113 (1992).
GREG T. HERMANSON ET AL., IMMOBILIZED AFFINITY LIGAND TECHNIQUES
166-169, 172, 173, 317-319, 354-359 (1992).
Graham Preece et al., Metalloproteinase-mediated Regulation of L-selectin
Levels on Leucocytes, 20 JOURNAL OF BIOLOGICAL CHEMISTRY 11634-11640
(1996).
Xianfang Zeng & Eli Ruckenstein, Trypsin Purification by
p-Aminobenzamidine Immobilized on Macroporous Chitosan Membranes,
37 IND. ENG. CHEM. RES. 159-165 (1998).
p-Aminobenzamidine,
http://www.chemicalbook.com/ProductChemicalPropertiesCB8384368_EN.
htm. (visited September 3, 2009).
I. Claims 1 and 10 stand rejected under 35 U.S.C. § 103(a) as
unpatentable over Hermanson, Zeng, Langlotz, and Preece (Ans. 8-11).
II. Claim 1 stands rejected under 35 U.S.C. § 103(a) as
unpatentable over Zeng and Langlotz (Ans. 5-8).
Appeal 2011-010437
Application 11/436,861

3
PRINCIPLES OF LAW
The Examiner’s rejections must be supported by a preponderance of
the evidence. See, e.g., Ethicon, Inc. v. Quigg, 849 F.2d 1422, 1427 (Fed.
Cir. 1988).
A rejection based on section 103 clearly must rest on a
factual basis . . . In making this evaluation, all facts must be
considered. The Patent Office has the initial duty of supplying
the factual basis for its rejection. . . . To the extent the Patent
Office rulings are so supported, there is no basis for resolving
doubts against their correctness. Likewise, we may not resolve
doubts in favor of the Patent Office determination when there
are deficiencies in the record as to the necessary factual bases
supporting its legal conclusion of obviousness.
In re Warner, 379 F.2d 1011, 1017 (CCPA 1967).
FINDINGS OF FACT
1. Hermanson teaches that “[t]he ligand p-aminobenzamidine (p-
AB [or PAB]) has been used extensively for the purification of urokinases,
serine proteases, plasminogen activators, and other similar enzymes”
(Hermanson 167).
According to Hermanson, “[i]mmobilized p-AB is best prepared by
using a spacer arm to extend the ligand some distance from the matrix [e.g.,
agarose gel]. This allows approaching enzymes to wrap around the
protruding ligand, reaching binding sites that may be somewhat buried
below the surface of the protein” (id.).
2. Zeng discloses an affinity membrane selective for trypsin (a
protease) comprising p-aminobenzamidine (PAB), immobilized on a
macroporous chitosan membrane (Zeng, Abstract).
According to Zeng, “succinic anhydride was first coupled to the
chitosan membrane to obtain succinic carboxyl groups as spacers” and “[t]he
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Application 11/436,861

4
succinylated chitosan membranes were then coupled with PAB” (id. at 160,
col. 1), as shown below:

(id. at 160, col. 2).
3. Langlotz discloses the coupling conditions for an epoxy-
activated membrane using protein A, immunoglobulin G, and soybean
trypsin inhibitor as a model system (Langlotz 107, col. 2). The functional
groups involved in immobilization are not discussed.
DISCUSSION
I.
Claims 1 and 10 stand rejected as unpatentable over Hermanson,
Zeng, Langlotz, and Preece.
The issue raised by this rejection is whether the Examiner has
established that it would have been obvious for one of ordinary skill in the
art to couple a protease inhibitor, e.g., p-aminobenzamidine to a membrane
containing epoxy groups, via the epoxy groups, given the evidence of
record.
The Examiner finds that Hermanson teaches that “it is essential to
completely remove undesirable proteases from biological solutions” for
many studies (Ans. 8), and “[e]xamples of [column chromatography] affinity
supports successfully used for this purpose include immobilized soybean
trypsin inhibitor and immobilized p-aminobenzamidine (PAB)” (id.).
Similarly, the Examiner finds that Zeng discloses a chitosan “membrane on
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Application 11/436,861

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which p-aminobenzamidine is immobilized” (id. at 5), and “[t]he PAB-
chitosan affinity membrane was used for adsorption of trypsin” (id. at 6).
The Examiner acknowledges that neither Hermanson nor Zeng
discloses PAB immobilized on an epoxy-functionalized membrane (id. at 6,
8). However, the Examiner finds that Langlotz discloses coupling proteins,
specifically, protein A, rabbit IgG, and soybean trypsin inhibitor, to epoxy-
activated membranes (id. at 9) by a simpler, less time-consuming procedure
than the procedures used by Hermanson and Zeng (id. at 10).
The Examiner concludes that it would have been obvious for one of
ordinary skill in the art to “substitute[] the epoxy-activated membrane of
Langlotz et al for the chitosan membrane taught by Zeng et al, and then
to couple the PAB to the epoxy-activated membrane to create a PAB
membrane for trypsin adsorption/purification” (Ans. 7), because “fewer
steps and less time would have been required in binding the protease
inhibitor(s) to the membrane” (id. at 10). The Examiner further finds that
“[t]here would have been reasonable expectation of success in immobilizing
at least one of the protease inhibitors . . . since the epoxy-activated
membrane of Langlotz et al. is shown to be suitable for binding molecules
via an amine terminal group (such as is found on PAB)” (id.).
Appellants contend that nothing in the prior art suggests that Zeng’s
PAB will bind an epoxy-activated membrane in a manner equivalent to the
proteins immobilized by Langlotz (i.e., protein A, rabbit IgG, and soybean
trypsin inhibitor) (App. Br. 4). More importantly, Appellants contend that
both Hermanson and Zeng use spacers between PAB and the support matrix,
and nothing in the evidence cited by the Examiner would have given one of
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6
ordinary skill in the art a reason to eliminate those spacers and bind the PAB
directly to the epoxy-activated membrane (id.).
Appellants have the better position. Even if we were to accept the
Examiner’s unsupported assertions that “the amine group of a protein reacts
with the epoxy group of the epoxy-activated membrane” (Ans. 6), and that
“PAB would react via [its] terminal amine group with the epoxy group of the
epoxy-activated membrane in the same manner as proteins” (id. at 7), we are
not persuaded that it would have been obvious for one of ordinary skill in
the art to immobilize PAB on an epoxy-activated membrane.
As discussed above, both Hermanson and Zeng use a spacer between
PAB and the support matrix (FFs 1, 2), and Hermanson explains that “[t]his
allows approaching enzymes [i.e., proteases to be removed from solution] to
wrap around the protruding ligand, reaching binding sites that may be
somewhat buried below the surface of the [protease]” (FF1). We see
nothing in the evidence of record that would lead one of skill in the art to
expect that the active site of PAB, which is much, much smaller than
Langlotz’s proteins, would still be available to bind approaching proteases
and remove them from solution, when bound directly to an epoxy-activated
membrane.
We find that the Examiner has not provided an adequate factual basis
to establish that it would have been obvious for one of ordinary skill in the
art to couple p-aminobenzamidine directly to an epoxy-activated membrane
via the membrane’s epoxy groups.
Accordingly, the rejection of the claims as unpatentable over
Hermanson, Zeng, Langlotz, and Preece is reversed.
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II.
Claim 1 stands rejected as unpatentable over Zeng and Langlotz.
The issue raised by this rejection is the same as the previous rejection,
and we find the evidence of record inadequate to support the rejection for the
same reasons discussed above.
The rejection of claim 1 as unpatentable over Zeng and Langlotz is
reversed.
SUMMARY
I. The rejection of claims 1 and 10 under 35 U.S.C. §103(a) as
unpatentable over Hermanson, Zeng, Langlotz, and Preece is reversed.
II. The rejection of claim 1 under 35 U.S.C. § 103(a) as
unpatentable over Zeng and Langlotz is reversed.

REVERSED

cdc