Ex Parte Wan et al

Board of Patent Appeals and Interferences

Sep 7, 2010

10292950 (B.P.A.I. Sep. 7, 2010)

UNITED STATES PATENT AND TRADEMARK OFFICE
__________

BEFORE THE BOARD OF PATENT APPEALS
AND INTERFERENCES
__________

Ex parte MIN WAN, MARK DAVID CHAVEZ,
and JEFFREY LEE SCHRIMSHER
__________

Appeal 2010-000598
Application 10/292,950
Technology Center 1600
__________

Before ERIC GRIMES, CAROL A. SPIEGEL, and
MELANIE L. McCOLLUM, Administrative Patent Judges.

McCOLLUM, Administrative Patent Judge.

DECISION ON APPEAL1
This is an appeal under 35 U.S.C. § 134 involving claims to an ion
exchange process and mixture. The Examiner has rejected the claims as

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.
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anticipated and/or obvious. We have jurisdiction under 35 U.S.C. § 6(b).
We reverse.
STATEMENT OF THE CASE
Claims 1-13 and 15-24 are pending and on appeal (App. Br. 2). We
will focus on claims 1, 18, and 22, which read as follows:
1. A process for protein purification by ion exchange
chromatography from a protein solution having a salt concentration
sufficient to significantly reduce the binding of the protein to the ion
exchange resin, the process, comprising the steps of:
a. adding from about 0.5% w/v to about 6 % w/v polyethylene
glycol (PEG) to a protein solution having a salt concentration
sufficient to significantly reduce the binding of the protein to an
ion exchange resin to form a protein-PEG solution; and,
b. binding the protein to the ion exchange resin by contacting the
ion exchange resin with the protein-PEG solution.
18. A process for the separation of a protein of interest by ion
exchange chromatography from a cell culture broth having a salt
concentration sufficient to significantly reduce the binding of the protein to
the ion exchange resin, the process comprising the steps of:
a. adding polyethylene glycol (PEG) to the cell culture broth to
form a PEG-cell culture broth;
b. binding the protein of interest to the ion exchange resin by
contacting the ion exchange resin with the PEG-cell culture
broth; and,
c. separating the protein of interest from the PEG-cell culture
broth.
22. A mixture comprising an ion exchange resin and a solution
comprising a cell culture broth[,] polyethylene glycol (PEG) in an amount
which is between about 1% w/v and 8% w/v of the cell culture broth, and a
protein; wherein the protein is bound to the ion exchange resin, and the cell
culture broth has a salt concentration sufficient to significantly reduce the
binding of the protein to the ion exchange resin in the absence of the PEG.
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Claims 1, 3, 5, 7, 9, 10, 12, 13, and 15-17 stand rejected under
35 U.S.C. § 102(b) as anticipated by Gagnon2 (Ans. 2).
Claims 1, 3, 7, 9, 10, 15, and 17 stand rejected under 35 U.S.C.
§ 102(b) as anticipated by Feng3 (Ans. 2).
Claims 1-13 and 15-24 stand rejected under 35 U.S.C. § 103(a) as
obvious in view of Gagnon and/or Feng (Ans. 2).
ANTICIPATION
Claim 1 is the only independent claim rejected for being anticipated.
The Examiner relies on both Gagnon and Feng for teaching all of the
features of claim 1 (Ans. 5-13).
Appellants argue that neither of the references discloses a protein
solution having a salt concentration sufficient to significantly reduce the
binding of the protein to an ion exchange resin (App. Br. 4).
Issue
Has the Examiner set forth a prima facie case that Gagnon or Feng
discloses the process of claim 1?
Findings of Fact
1. Gagnon discloses that “the addition of poly(ethylene glycol)
(PEG) to the mobile phase systematically and significantly alters the

2 Pete Gagnon et al., Method for obtaining unique selectivities in ion-
exchange chromatography by addition of organic polymers to the mobile
phase, 743 J. OF CHROMATOGRAPHY 51-55 (1996).
3 Xiao-Li Feng et al., Polyethylene glycol improves the purification of
recombinant human tumor necrosis factor during ion exchange
chromatography, 12 BIOTECHNOLOGY TECHNIQUES 289-293 (1998).
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retention behaviour of proteins in ion-exchange chromatography”
(Gagnon 51: Abstract).
2. In particular, Gagnon discloses:
Anion-exchange experiments were conducted in a base binding
buffer of 0.05 M Tris, pH 8.6, and eluted in a linear gradient to
0.05 M Tris, 1.0 M sodium chloride, pH 8.6. The base buffers
for cation-exchange were 0.05 M MES, pH 6.0 and 0.05 M
MES, 1.00 M sodium chloride, pH 6.0. Series of experiments
were conducted with PEG formulated into the base buffers at
various incremental levels.
(Id. at 52.)
3. Feng discloses the effect of PEG on tumor necrosis factor-α
(TNF-α) purification by anion exchange chromatography (Feng 291).
4. In particular, Feng discloses using “10 mM Tris/HCl containing
different concentration[s] of PEG” as an equilibrium buffer and performing
step-wise elution with a buffer containing 75 mM NaCl (id. at 290-291).
Principles of Law
“A claim is anticipated only if each and every element as set forth in
the claim is found, either expressly or inherently described, in a single prior
art reference.” Verdegaal Bros., Inc. v. Union Oil Co. of California, 814
F.2d 628, 631 (Fed. Cir. 1987). “[T]he Patent Office has the initial burden
of coming forward with some sort of evidence tending to disprove novelty.”
In re Wilder, 429 F.2d 447, 450 (CCPA 1970).
Analysis
Gagnon and Feng both disclose adding PEG to a protein solution
(Findings of Fact (FF) 1-4). Gagnon and Feng also disclose elution buffers
comprising sodium chloride (FF 2 & 4). We do not dispute that these
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elution buffers provide protein solutions having a salt concentration
sufficient to significantly reduce the binding of the protein to an ion
exchange resin. However, the Examiner has not set forth a prima facie case
that Gagnon or Feng teaches adding PEG to a protein solution having such a
salt concentration to form a protein-PEG solution and binding the protein to
the ion exchange resin by contacting the ion exchange resin with the protein-
PEG solution, as required by claim 1. Instead, Gagnon and Feng both teach
that salt is added to a protein-PEG solution to elute the protein from the ion
exchange resin (FF 2 & 4).
Conclusion
The Examiner has not set forth a prima facie case that Gagnon or
Feng discloses the process of claim 1. We therefore reverse the anticipation
rejections.
OBVIOUSNESS
The Examiner finds that Feng’s “disclosure of employing PEG in the
presence of a buffer solution for the purification of proteins using anionic
exchange chromatography renders Claims 1-4, 7-11, 15, 17-22 and 24 prima
facie obvious to one of ordinary skilled [sic] in the art” (Ans. 14).
The Examiner also find that Gagnon “teaches the retention behavior
and the advantages of employing PEG in ion exchange chromatography for
protein retention with PEG having a molecular weight in the range of 400 to
1000” (id.). The Examiner concludes that “[i]t would have been prima facie
obvious to employ the proteins . . . of Feng et al for the proteins of ....
Gagnon et al teaches the purification of proteins by ion exchange
chromatography” (id.).
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Appellants argue that “in Gagnon et al a commercially available
(purified) protein is used in the experimentations therein, and in Feng et al a
protein solution is isolated by removing the culture broth and reconstituting
the cellular material in a TE buffer” (App. Br. 5).
Appellants also argue that “[n]one of the cited reference[s] teaches or
suggests, either alone or in combination, the claimed invention of purifying a
protein by ion exchange chromatography from a protein solution or cell
broth having a salt concentration sufficient to significantly reduce
binding of the protein to the ion exchange resin” (id. at 7-8).
Issues
Has the Examiner set forth a prima facie case that Gagnon and/or
Feng suggest a mixture comprising an ion exchange resin and a solution
comprising a cell culture broth?
Has the Examiner set forth a prima facie case that Gagnon and/or
Feng suggest adding PEG to a protein solution or cell culture broth having a
salt concentration sufficient to significantly reduce the binding of the protein
to an ion exchange resin and binding the protein to the ion exchange resin by
contacting the ion exchange resin with the protein-PEG solution or PEG-cell
culture broth?
Findings of Fact
5. Feng discloses that recombinant E coli harboring the gene
TNF-α was grown on Luria broth, cells were collected by centrifugation,
washed, and resuspended in 10 mM Tris/HCl buffer with 1 mM EDTA, cells
were disrupted, the resulting cell homogenate was centrifuged to remove cell
debris, and clear supernatant was used for further processing (Feng 289).
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6. The Examiner does not point to any teaching in Gagnon
showing that the proteins subjected to ion exchange chromatography are in
cell culture broth.
Principles of Law
“In rejecting claims under 35 U.S.C. § 103, the examiner bears the
initial burden of presenting a prima facie case of obviousness. Only if that
burden is met, does the burden of coming forward with evidence or
argument shift to the applicant.” In re Rijckaert, 9 F.3d 1531, 1532 (Fed.
Cir. 1993) (citation omitted).
Analysis
Feng discloses separating the protein from the Luria broth (FF 5).
The Examiner does not point to any teaching in Gagnon showing that the
proteins subjected to ion exchange chromatography are in cell culture broth
(FF 6), nor has the Examiner explained why doing so would have been
obvious. Thus, the Examiner has not set forth a prima facie case that
Gagnon and/or Feng teach or suggest a mixture comprising an ion exchange
resin and a solution comprising a cell culture broth.
In addition, as discussed above, the Examiner has not set forth a prima
facie case that Gagnon or Feng teaches adding PEG to a protein solution
having a salt concentration sufficient to significantly reduce the binding of
the protein to an ion exchange resin to form a protein-PEG solution and
binding the protein to the ion exchange resin by contacting the ion exchange
resin with the protein-PEG solution, nor has the Examiner explained why it
would have been obvious to do so. The Examiner also has not explained
why it would have been obvious to add PEG to a cell culture broth having
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such a salt concentration and bind the protein of interest to the ion exchange
resin by contacting the ion exchange resin with the PEG-cell culture broth.
Conclusion
The Examiner has not set forth a prima facie case that Gagnon and/or
Feng suggest a mixture comprising an ion exchange resin and a solution
comprising a cell culture broth. We therefore reverse the obviousness
rejection of claim 22 and of claims 23 and 24, which depend therefrom.
In addition, the Examiner has not set forth a prima facie case that
Gagnon and/or Feng suggest adding PEG to a protein solution or cell culture
broth having a salt concentration sufficient to significantly reduce the
binding of the protein to an ion exchange resin and binding the protein to the
ion exchange resin by contacting the ion exchange resin with the protein-
PEG solution or PEG-cell culture broth. We therefore also reverse the
obviousness rejections of claims 1 and 18 and of claims 2-13, 15-17, and 19-
21, which depend from either claim 1 or claim 18.

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REVERSED

alw

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