Ex Parte Hermentin et al

Board of Patent Appeals and Interferences

Jul 8, 2010

10682199 (B.P.A.I. Jul. 8, 2010)

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.
10/682,199 10/10/2003 Peter Hermentin 06478.1495 1253
22852 7590 07/09/2010
FINNEGAN, HENDERSON, FARABOW, GARRETT & DUNNER
LLP
901 NEW YORK AVENUE, NW
WASHINGTON, DC 20001-4413
EXAMINER
NGUYEN, BAO THUY L
ART UNIT PAPER NUMBER
1641
MAIL DATE DELIVERY MODE
07/09/2010 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 BOARD OF PATENT APPEALS
AND INTERFERENCES
__________

Ex parte PETER HERMENTIN, THOMAS CUESTA-LINKER, and
KARL-HEINZ SCHMIDT
__________

Appeal 2009-015014
Application 10/682,199
Technology Center 1600
__________

Before ERIC GRIMES, DONALD E. ADAMS, and JEFFREY N.
FREDMAN, Administrative Patent Judges.

GRIMES, Administrative Patent Judge.

DECISION ON APPEAL1
This is an appeal under 35 U.S.C. § 134 involving claims to a method
for analyzing multimer-forming proteins by gel electrophoresis. The

1 The two-month time period for filing an appeal or commencing a civil
action, as recited in 37 C.F.R. § 1.304, or for filing a request for rehearing,
as recited in 37 C.F.R. § 41.52, begins to run from the “MAIL DATE”
(paper delivery mode) or the “NOTIFICATION DATE” (electronic delivery
mode) shown on the PTOL-90A cover letter attached to this decision.
Appeal 2009-015014
Application 10/682,199

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Examiner has rejected the claims as obvious. We have jurisdiction under 35
U.S.C. § 6(b). We affirm-in-part.
STATEMENT OF THE CASE
Claims 16-25, 27-28, 30-31, 33, and 35 are on appeal. Claims 16 and
25 are representative and read as follows:
16. A method for the determination of multimers of multimer-forming
proteins by gel electrophoresis, comprising
fractionating a sample containing von Willebrand factor or fibrinogen
into multimer bands by submarine electrophoresis in agarose gel, wherein
the agarose gel is continuous, homogeneous and free of lumps,
visualizing multimer bands by a dye in the gel, and
optionally quantifying the dyed multimer bands.

25. [The method of claim 16,] wherein the gel electrophoresis is
carried out at temperatures between 8°C and 12°C.

The claims stand rejected under 35 U.S.C. § 103(a) as follows:
• claims 16-24, 27-28, 30-31, 33 and 35 in view of Shainoff2 and
Bhat;3 and
• claim 25 in view of Shainoff, Bhat and Perrella.4

2 J. R. Shainoff, Electrophoresis and Direct Immunoprobing on Glyoxyl
Agarose and Polyacrylamide Composites, in A. Charmbach et al. (eds.) 6
ADVANCES IN ELECTROPHORESIS 61-177, VCH (New York), 1993.
3 S. P. Bhat et al., Use of “Submarine” Gel Electrophoresis for Running
Multiple Two-Dimensional Protein Gels, 170 ANAL. BIOCHEM. 105-109
(1988).
4 M. Perrella et al., Low-Temperature Electrophoresis Methods, 259
METHODS IN ENZYMOL. 468-487 (1995).

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I.
Issue
The Examiner has rejected claims 16-24, 27-28, 30-31, 33 and 35
under 35 U.S.C. § 103(a) as Shainoff and Bhat. The claims have not been
argued separately and therefore stand or fall together. 37 C.F.R.
§ 41.37(c)(1)(vii).
The Examiner finds that Shainoff discloses fractionating von
Willebrand factor multimers by continuous, homogeneous agarose gel
electrophoresis (Ans. 3), as well as “visualizing multimer bands by a dye in
the gel” (id. at 4). The Examiner finds that Bhat discloses “the use of
‘submarine’ electrophoresis for resolving proteins” (id.). The Examiner
concludes that it “would have been obvious for a person of ordinary skill in
the art to replace the electrophoretic protocol of Shainoff with a ‘submarine’
method because Bhat … discovered that the ‘submarine’ method allows for
stacking of multiple gels allowing for multiple simultaneous runs” (id.).
Appellants contend that the cited references would not suggest the
method of claim 16 because Shainoff describes a variety of electrophoresis
procedures and thus requires picking and choosing to arrive at the invention
of claim 16 (Appeal Br. 9-10). Appellants also contend that Shainoff
discloses a gel made of glyoxyl agarose, not an agarose gel as claimed (id. at
11-12), and that Bhat “is directed to an entirely different electrophoresis
procedure” that involves two-dimensional protein electrophoresis and
polyacrylamide gels (id. at 13).
The issue with respect to this rejection is: Does the evidence of
record support the Examiner’s conclusion that Shainoff and Bhat would
have made obvious a method meeting the limitations of claim 16?
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Findings of Fact
1. Shainoff discloses the development of glyoxyl agarose gels for
“direct immunoprobing, because of need to analyze fibrinogen derivatives
that were virtually completely resistant to blot-transfer” (Shainoff, 66).
2. Shainoff discloses that a “2% gel has been found useful for
separating von Willebrand factor multimers” (id. at 78).
3. Shainoff discloses that a commercially available product comprises
a mixture of glyoxyl agarose and regular agarose (id. at 72).
4. Shainoff discloses that the gels may be continuous (id. at 75).
5. Shainoff discloses protein staining of glyoxyl agarose gels with
Coomassie Blue (id. at 98).
6. Bhat discloses that “[a]n apparatus commonly used for the
electrophoresis of submerged agarose gels was used to separate proteins.…
The units for submerged horizontal gel electrophoresis are easily made or
are inexpensively available commercially.” (Bhat, abstract.)
Analysis
Claim 16 is directed to a method for determining multimers of von
Willebrand factor or fibrinogen by fractionating a sample into multimer
bands by submarine agarose gel electrophoresis and visualizing multimer
bands using a dye.
Shainoff discloses a method for fractionating von Willebrand factor
multimers, among other things, by glyoxyl agarose gel electrophoresis in a
continuous gel system. Shainoff also discloses visualizing proteins in a gel
using a dye. Shainoff does not specifically disclose using submarine gel
electrophoresis, but Bhat discloses that submerged, or submarine, agarose
gels were commonly used in the art to separate proteins. In view of these
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disclosures, it would have been obvious to one of skill in the art to carry out
Shainoff’s electrophoretic fractionation using submarine gel electrophoresis
because Bhat discloses that submarine gel electrophoresis was commonly
used with agarose gels.
Appellants contend that Shainoff is a review article that describes a
variety of electrophoresis procedures and thus requires using hindsight to
pick and choose from the disclosed element in order to arrive the invention
of claim 16 (Appeal Br. 9-10). Appellants further contend that Shainoff
discloses a preference for immunoprobing of the gels rather than dye
staining (Reply Br. 4).
This argument is not persuasive. Although Shainoff does provide a
number of options for protein separation and visualization, it discloses that
continuous agarose gels were conventional for separating proteins and dye
staining was conventional for visualizing them. It also discloses that glyoxyl
agarose gels were known for separating fibrinogen derivatives and von
Willebrand factor multimers. Appellants have provided no persuasive
reason for concluding that combining these conventional elements would not
have been obvious. Although Shainoff discloses that immunostaining
provides “greater sensitivity and intensity of staining” (Shainoff 79, legend
to Fig. 4), it shows that dye staining is also effective for visualizing
fibrinogen in a gel (id. at Fig. 4). Appellants have pointed to no evidence
showing that dye staining would not be effective for visualizing multimers
of fibrinogen or von Willebrand factor.
Appellants also contend that Shainoff does not suggest regular
agarose alone, as opposed to glyoxyl agarose (Appeal Br. 8-9; Reply Br. 3).
Appeal 2009-015014
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This argument is not persuasive. During examination, claim terms are
to be given the broadest reasonable interpretation consistent with the
specification. The Specification does not define the term “agarose” to
exclude agarose derivatives. Thus, the broadest reasonable interpretation of
the term encompasses a derivatized agarose such as glyoxyl agarose, and the
blend of agarose and derivatized agarose disclosed in Shainoff.
Finally, Appellants argue that one of skill in the art would not have
been motivated to combine the cited references because Bhat “is directed to
an entirely different electrophoresis procedure” that involves two-
dimensional protein electrophoresis and polyacrylamide gels (Appeal Br.
13).
This argument is not persuasive. Shainoff discloses agarose gel
electrophoresis and Bhat discloses that a submerged gel (submarine gel)
apparatus is commonly used for agarose gel electrophoresis. The fact that
Bhat also discloses an additional use for a submarine gel apparatus does not
detract from the obviousness of combining Bhat’s submarine electrophoresis
method with Shainoff’s agarose gel.
Conclusion of Law
The evidence of record supports the Examiner’s conclusion that
Shainoff and Bhat would have made obvious a method meeting the
limitations of claim 16.
II.
Issue
The Examiner has rejected claim 25 under 35 U.S.C. § 103(a) as
being obvious in view of Shainoff, Bhat and Perrella.
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The Examiner relies on Shainoff and Bhat as discussed above. The
Examiner finds that Perrella discloses “the use of temperature to modify
electrophoresis” (Ans. 5) and concludes that it would have been obvious to
modify the electrophoretic method suggested by Shainoff and Bhat “by
modifying temperature because Perrella … teach[es] that the use of
temperature to modify electrophoresis allows for probing of ‘intermediate
stages of ligation’ and ‘quaternary structural changes’” (id.).
Appellants contend that Perrella would not suggest a temperature
range of 8°C to 12°C because Perrella discusses the electrophoresis of
hemoglobin in a polyacrylamide gel system “at temperatures below the
freezing point of water using cryosolvents” and thus would not have
suggested the optimization of electrophoresis of a different protein in a
different gel system (Appeal Br. 14-15).
The issue with respect to this rejection is: Does the evidence of record
support the Examiner’s conclusion that the cited references would have
made it obvious to carry out the electrophoresis suggested by Shainoff and
Bhat at a temperature between 8°C and 12°C?
Additional Findings of Fact
7. Perrella discloses that “[s]tudies of hemoglobin at intermediate
stages of ligation are difficult because of the mobility of the heme ligands,
which reversibly associate and dissociate from the subunits, and the ligation-
linked reversible dissociation of the hemoglobin tetramers into
uncooperative dimers” (Perrella, 469).
8. Perrella discloses “cryogenic quenching and electrophoresis
techniques to analyze mixtures of species in a partial state of ligation either
at equilibrium or under dynamic conditions” (id. at 469-470).
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9. Perrella discloses that a
breakthrough in cryogenic electrophoresis was achieved by the
use of copolymers of acrylamide and methyl or ethyl acrylate.
… Electrophoretic separations of hemoglobin hybrids have
been carried out at -45°.… However, because the mobility of
hemoglobin during the approach to focusing equilibrium is low,
isoelectric focusing is usually carried out at -25°.
(Id. at 472.)
Analysis
Claim 25 is directed to the method of claim 16, wherein the gel
electrophoresis is carried out at temperatures between 8°C and 12°C. The
Examiner finds that Perrella suggests optimizing the temperature of the
electrophoresis suggested by Shainoff and Bhat.
Appellants argue that Perrella’s “electrophoresis of hemoglobin in
copolymers of acrylamide and methyl or ethyl acrylate at temperatures
below the freezing point of water using cryosolvents” would not have
suggested carrying out agarose gel electrophoresis of von Willebrand factor
or fibrinogen at 8°C to 12°C (Appeal Br. 14-15).
Appellants’ arguments are persuasive. Perrella discusses the
electrophoretic fractionation of hemoglobin, rather than von Willebrand
factor or fibrinogen, in a gel system that is different from that used by
Shainoff and Bhat, and at significantly different temperatures than those
required by claim 25. The Examiner has not adequately explained why
Perrella would have made obvious the temperature range recited in claim 25.
Conclusion of Law
The evidence of record does not support the Examiner’s conclusion
that the cited references would have made it obvious to carry out the
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electrophoresis suggested by Shainoff and Bhat at a temperature of 8°C to
12°C.
SUMMARY
We affirm the rejection of claims 16-24, 27-28, 30-31, 33 and 35
under 35 U.S.C. § 103(a). However, we reverse the rejection of claim 25
under 35 U.S.C. § 103(a).
TIME PERIOD FOR RESPONSE
No time period for taking any subsequent action in connection with
this appeal may be extended under 37 C.F.R. § 1.136(a).

AFFIRMED-IN-PART

lp

FINNEGAN, HENDERSON, FARABOW, GARRETT & DUNNER
LLP
901 NEW YORK AVENUE, NW
WASHINGTON DC 20001-4413