Ex Parte Bolli et al

Patent Trial and Appeal Board

Dec 9, 2013

10579357 (P.T.A.B. Dec. 9, 2013)

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.
10/579,357 05/16/2006 Reinhard Bolli 06478.1507 2138
22852 7590 12/09/2013
FINNEGAN, HENDERSON, FARABOW, GARRETT & DUNNER
LLP
901 NEW YORK AVENUE, NW
WASHINGTON, DC 20001-4413
EXAMINER
KIM, YUNSOO
ART UNIT PAPER NUMBER
1644
MAIL DATE DELIVERY MODE
12/09/2013 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 REINHARD BOLLI,
GERHARD HODLER, and REGULA STYGER
__________

Appeal 2012-005769
Application 10/579,357
Technology Center 1600
__________

Before FRANCISCO C. PRATS, ERICA A. FRANKLIN, and
JOHN G. NEW, Administrative Patent Judges.

PRATS, Administrative Patent Judge.

DECISION ON APPEAL
This appeal1 under 35 U.S.C. § 134 involves claims to stable
polyclonal IgG preparations. The Examiner rejected the claims for
obviousness.
We have jurisdiction under 35 U.S.C. § 6(b). We reverse.

1 Appellants identify CSL Behring AG as the real party in interest. (App.
Br. 4.)
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Application 10/579,357

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STATEMENT OF THE CASE
Claims 29-45 stand rejected and appealed (see App. Br. 6). Claims 29
and 41, the independent claims, illustrate the appealed subject matter and
read as follows:
29. A stable polyclonal IgG preparation, wherein the preparation
comprises polyclonal IgG and a stabilizer comprising proline, has a
pH of about 4.2 to about 5.4, and does not comprise nicotinamide.

41. A stable liquid polyclonal IgG preparation, wherein the
preparation comprises polyclonal IgG and a stabilizer consisting
essentially of proline, wherein the preparation has a pH of about 4.2 to
about 5.4, and wherein the preparation is not lyophilized prior to
administration.

The sole rejection before us for review is the Examiner’s rejection of
claims 29-45 under 35 U.S.C. § 103(a) as obvious over Lam2 and Schulke3
(Ans. 4-7).
DISCUSSION
The Examiner found that Lam described a polyclonal IgG preparation
having the pH recited in claim 29, but conceded that the preparation differed
from claim 29 in that it lacked a stabilizer that contained proline (see Ans.
5). To address that deficiency, the Examiner cited Schulke as describing an
antibody formulation that contained a histidine buffer and proline at about
pH 5.5 (id.).
Based on these teachings, the Examiner concluded that an ordinary
artisan would have considered it obvious “to add proline as a stabilizer as

2 U.S. Patent No. 6,171,586 B1 (issued January 9, 2001).
3 U.S. Patent App. Pub. No. 2005/0142139 A1 (filed March 19, 2004).
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taught by [Schulke] to the antibody formulation as taught by [Lam]” (id. at
7). The Examiner reasoned:
Therefore, it is prima facie obvious to combine two
compositions each of which is taught by prior art to be useful
for same purpose in order to form third composition that is to
be used for very same purpose; idea of combining them flows
logically from their having been individually taught in prior art.

(Id. (citing In re Kerkhoven, 626 F.2d 846, 850 (CCPA 1980); MPEP §
2144.06.)) The Examiner further reasoned that, “[o]ne of ordinary skill in
the art at the time the invention was made would have been motivated to do
so because the addition of proline improves stability of protein upon storage
and delivery by reducing aggregation” (id.).
Appellants argue, for a number of reasons, that the Examiner failed to
make out a prima facie case of obviousness (App. Br. 20-24). The Examiner
responds that
[A]ll the claimed elements (antibody and proline) were known
in the prior art and one skilled in the art could have arrived at
the claimed invention by using known methods (stabilization of
protein) with no change in their respective functions and the
combination would have yielded nothing more than predictable
results of yielding more stable composition.

(Ans. 12.)
“In proceedings before the Patent and Trademark Office, the
Examiner bears the burden of establishing a prima facie case of obviousness
based upon the prior art.” In re Fritch, 972 F.2d 1260, 1265 (Fed. Cir.
1992).
In KSR Int’l Co. v. Teleflex Inc., 550 U.S. 398, 415 (2007), while the
Supreme Court emphasized “an expansive and flexible approach” to the
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obviousness question, it also reaffirmed the importance of determining
“whether there was an apparent reason to combine the known elements in
the fashion claimed by the patent at issue.” Id. at 418 (emphasis added).
Thus, “[o]bviousness requires more than a mere showing that the prior
art includes separate references covering each separate limitation in a claim
under examination.” Unigene Laboratories, Inc. v. Apotex, Inc., 655 F.3d
1352, 1360 (Fed. Cir. 2011).
Instead, “[i]n determining whether obviousness is established by
combining the teachings of the prior art, the test is what the combined
teachings of the references would have suggested to those of ordinary skill
in the art.” In re GPAC Inc., 57 F.3d 1573, 1581 (Fed. Cir. 1995) (internal
quotations omitted).
In the instant case, we are not persuaded that the cited references
would have suggested preparing the compositions recited in claims 29 and
41.
Lam describes a “stable aqueous pharmaceutical formulation
comprising a therapeutically effective amount of an antibody not subjected
to prior lyophilization, a buffer maintaining the pH in the range from about
4.5 to about 6.0, a surfactant and a polyol” (Lam, col. 2, ll. 25-29). As the
Examiner found, Lam discloses that the antibodies in its compositions can
be polyclonal antibodies (see id. col. 11, ll. 30-58).
Schulke describes compositions containing CD4-IgG2, which is an
anti-HIV “chimeric protein in which polypeptides comprising both the heavy
and light chain constant regions of human IgG2 have been fused to the VI
and V2 gp120-binding domains of human CD4” (Schulke, ¶ 5). Schulke
discloses that pharmaceutical formulations of its protein can include “a
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histidine buffer and an amino acid stabilizing agent” (id. at ¶ 9). As the
Examiner found, Schulke further discloses that “[e]xamples of amino acid
stabilizing agents include alanine, glycine, proline[,] and glycylglycine” (id.
at ¶ 32).
We are not persuaded, however, that Schulke’s disclosure of using
proline as a stabilizer for a therapeutic preparation containing only a single
species of a chimeric protein would have prompted an ordinary artisan to
also include proline in Lam’s polyclonal antibody preparation, particularly
given Lam’s disclosure that its compositions were adequately stabilized
using the ingredients described therein (see Lam col. 6, ll. 1-5). While the
Examiner urged that proline would have reduced protein aggregation (see
Ans. 7), the Examiner does not direct us to any clear or specific teaching to
that effect in either reference.
Moreover, the Examiner points to no clear or specific teaching in
either reference suggesting that an ordinary artisan would have considered
proline to be an equivalent stabilizer to the stabilizers used in Lam. Nor has
the Examiner otherwise explained, with any specificity, why an ordinary
artisan would have considered the stabilizers in the two cited references to
be equivalents, such that an ordinary artisan would have been prompted to
use Schulke’s proline in Lam’s compositions. Further, while we note
Schulke’s teaching that proline was a suitable stabilizer for its particular
protein construct, the Examiner has not directed us to any persuasive
evidence suggesting that an ordinary artisan would have considered proline
to be a stabilizer generically suitable for therapeutic protein or antibody
preparations.
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Thus, as we are not persuaded that the cited references would have
prompted an ordinary artisan to include proline as a component of Lam’s
polyclonal antibody preparation, we reverse the Examiner’s obviousness
rejections of claims 29 and 41, and their dependent claims.

REVERSED

cdc