Ex Parte Sun et al

Patent Trial and Appeal Board

Mar 1, 2016

10958595 (P.T.A.B. Mar. 1, 2016)

UNITED STA TES p A TENT AND TRADEMARK OFFICE
APPLICATION NO. FILING DATE
10/958,595 10/06/2004
25291 7590 03/03/2016
WYETHLLC
PFIZER INTELLECTUAL PROPERTY
235 East 42nd Street
NY0-235/09/S-20
NEW YORK, NY 10017
FIRST NAMED INVENTOR
Shujun Sun
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
ATTORNEY DOCKET NO. CONFIRMATION NO.
PC060075A 1799
EXAMINER
KIM,YUNSOO
ART UNIT PAPER NUMBER
1644
NOTIFICATION DATE DELIVERY MODE
03/03/2016 ELECTRONIC
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.
Notice of the Office communication was sent electronically on above-indicated "Notification Date" to the
following e-mail address( es):
-IPGSMadisonDocketing@pfizer.com
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
BEFORE THE PATENT TRIAL AND APPEAL BOARD
Ex parte SHUJUN SUN, CHRISTOPHER GALLO, and BRIAN KELLEY
Appeal2013-004451
Application 10/958,595
Technology Center 1600
Before DONALD E. ADAMS, MELANIE L. McCOLLUM, and
JACQUELINE T. HARLOW, Administrative Patent Judges.
ADAMS, Administrative Patent Judge.
DECISION ON APPEAL 1
This appeal under 35 U.S.C. § 134(a) involves claims 1-14, 65-80,
164--169, and 171-192 (App. Br. 4; August 16, 2011 Office Action 2).2
Examiner entered rejections under 35 U.S.C. § 103(a). We have jurisdiction
under 35 U.S.C. § 6(b).
We REVERSE.
1 Appellants identify the Real Party in Interest as Wyeth LLC (App. Br. 2).
2 We recognize Appellants' reference to "[a]n amendment to cancel claim
165" (App. Br. 4). Examiner, however, failed to comment on Appellants'
amendment and included claim 165 among the rejected claims in the
Answer. Therefore, for the purposes of this Appeal, we treat claim 165 as
pending on this record.
Appeal2013-004451
Application 10/958,595
STATEMENT OF THE CASE
Appellants disclose "methods of removing high molecular weight
aggregates from an antibody preparation using hydroxyapatite
chromatography" (Spec. i-f 2). Claims 1, 65, 166, and 179 are representative
and reproduced in the Claims Appendix of Appellants' Brief.
Claims 1-7, 12-14, 65-73, 78-80, 164--169, 171, 172, 177-186, and
190-192 stand rejected under 35 U.S.C. § 103(a) as unpatentable over the
combination of Gagnon,3 Giovannini,4 Kennedy, 5 and Williams. 6
Claims 8-11, 74--77, 173-176, and 187-189 stand rejected under 35
U.S.C. § 103(a) as unpatentable over the combination of Gagnon,
Giovannini, Kennedy, Williams, and Basi.7
ISSUE
Does the preponderance of evidence relied upon by Examiner support
a conclusion of obviousness?
FACTUAL FINDINGS (FF)
FF 1. Gagnon discloses that "[h ]ydroxyapatite chromatography (HAC) []
has failed to attain the popularity of ion exchange" chromatography (Gagnon
87).
3 Pete Gagnon, Purification Tools for Monoclonal Antibodies, Ch. 5, 87-102
(1996).
4 Roberto Giovannini and Ruth Freitag, Comparison of different types of
ceramic hydroxyapatite for the chromatographic separation of plasmid DNA
and a recombinant anti-Rhesus D antibody, 9 Bioseparation 359-368
(2001).
5 Robert M. Kennedy, Hydrophobic-Interaction Chromatography, Current
Protocols in Protein Science 8.4.1-8.4.21 (2000).
6 Alan Williams and Verna Frasca, Ion-Exchange Chromatography, 8.2.1-
8.2.30 (1999).
7 Basi et al., US 2003/0165496 Al, published Sept. 4, 2003.
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Application 10/958,595
FF 2. Gagnon discloses that "[u]nlike adsorptive chemistries where a
reactive ligand is affixed to a 'neutral' matrix, hydroxyapatite is both the
ligand and the matrix" (Gagnon 87).
FF 3. Gagnon discloses that the formula for HAC "is Ca1o(P04)6(0H)2.[]
The functional groups comprise positively charged pairs of crystal calcium
ions (C-sites) and clusters of 6 negatively charged oxygen atoms associated
with triplets of crystal phosphates (P-sites ). C-sites, P-sites, and hydroxyls
are distributed in a fixed pattern on the crystal surface" (Gagnon 87; see also
Giovannini 359 ("In contrast[] to most other chromatographic phases, HAP
[ (hydroxyapatite)] is an inorganic material, usually assumed to have the
formula Ca1o(P04)6(0H)2")).
FF 4. Giovannini discloses that the
[r]etention mechanisms for biomacromolecules on HAP are
complex, since two types of interaction with the surface are
possible[]. Substances may, for example, interact with the
phosphate moieties (P-sites) on the HAP surface; this
interaction requires either positive charges or groups with high
phosphate affinity on the retained molecule. The interaction of
negatively charged molecules, such as acidic proteins and
DNA, is also possible on HAP[]. In this case, an interaction of
calcium-chelating or -binding groups on the retained molecule
with the calcium-based C-sites on the HAP-surface is assumed
to be responsible for the retention.
(Giovannini 359-360.)
FF 5. Giovannini discloses that because, "the P-site interaction is assumed
to be due to an electrostatic type of interaction, while the C-site interaction
involves chelating of the calcium groups, a gradient of increasing phosphate
concentration is usually employed to elute all interacting substances from an
HAP-column" (Giovannini 360 (emphasis added)).
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Application 10/958,595
FF 6. In developing a methodology to purify a particular protein, i.e., an
antibody, from an HAC column, Gagnon discloses that "[ m ]ethod
development for HAC follows the same general format as IEC [(ion-
exchange chromatography)]," wherein "[t]he first step is to determine
whether the antibody behaves as dominantly basic or dominantly acidic"
(Gagnon 97; see id. at 99-100 ("With proper[] method development
customized to its unique characteristics, HAC offers process capabilities on
a par with the best alternatives"); cf Ans. 9 ("Gagnon [] teaches that
hydroxyapatite chromatography generally follows the same general format
as in ion exchange chromatography")).
FF 7. Examiner finds that Gagnon fails to suggest the elution of antibodies
from a HAP column with a "constant concentration of phosphate of lmM to
20mM" (Ans. 5).
FF 8. Examiner finds that "the chromatography art recognizes combination
of hydrophobic interaction chromatography and/or ion exchange
chromatography with hydroxyapatite chromatography" (Ans. 9).
FF 9. Examiner relies on Kennedy to disclose methods relating to
hydrophobic-interaction chromatography (Ans. 5).
FF 10. Examiner relies on Williams to disclose methods relating to ion-
exchange chromatography (Ans. 5-6).
FF 11. Examiner finds that Gagnon discloses sample and column
equilibration buffers comprising 5mM sodium phosphate, with or without
NaCl at pH 6.8 (see Ans. 4 and 9).
FF 12. Giovannini illustrates the elution profile of an antibody from a
hydroxyapatite column, wherein Giovannini eluted IgG from the column in a
buffer comprising approximately 3 5--40 mM phosphate (see Giovannini
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Application 10/958,595
366:Figure 5, panel (a); id. at 367:Figure 5, Legend; id. at 365; Br. 19; cf
Ans. 9 (Examiner interprets Giovannini's Figure 5, panel (a) to illustrate
"the elution of IgG at about 22-23 minutes," which, according to Examiner
represents a phosphate concentration of "about 20-30mM"); Ans. 5
(Giovannini discloses a method of purifying antibody from a hydroxyapatite
column "with an elution buffer comprising about 20 mM sodium phosphate
and 1 M NaCl at pH 6")).
FF 13. Examiner finds that the combination of Gagnon, Giovannini,
Kennedy, and Williams fails to suggest "the use of anti-Abeta" and an
antibody monomer (Ans. 7).
FF 14. Examiner finds that Basi discloses an "anti-Abeta antibody" (Ans.
7).
ANALYSIS
The combination of Gagnon, Giovannini, Kennedy, and Williams:
Based on the combination of Gagnon, Giovannini, Kennedy, and
Williams, Examiner concludes that, at the time Appellants' invention was
made, it would have been prima facie obvious "to employ a step gradient
(holding a constant concentration) as taught by Kennedy and Williams []
into the antibody purification method using hydroxyapatite chromatography
taught by Gagnon and Giovanni[ni]" (Ans. 6).
Claims 1-14and164:
The method of Appellants' claim 1 comprises, inter alia, an "elution
buffer [that] comprises a constant concentration of phosphate" (see
Appellants' claim 1 ). Appellants' claims 2-14 and 164 depend directly or
indirectly from Appellants' claim 1.
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Application 10/958,595
Appellants' contend that Examiner failed to establish an evidentiary
basis on this record to support a conclusion that a person of ordinary skill in
this art would have reasonably expected to elute an antibody from a
hydroxyapatite resin with a buffer that comprises a constant concentration of
phosphate (see Br. 12). We agree.
Examiner concedes that Gagnon fails to suggest the elution of an
antibody from a hydroxyapatite column with a buffer comprising a constant
concentration of phosphate (FF 7). To the contrary, Giovannini discloses
that "a gradient of increasing phosphate concentration is usually employed
to elute all interacting substances from [a hydroxyapatite]-column" (FF 5).
We recognize, but are not persuaded by, Examiner's reliance on
Kennedy and Williams to fill the void in the combination of Gagnon and
Giovannini and assertion that the prior art suggests the purification of
proteins, including antibodies, using a combination of hydroxyapatite
chromatography and other chromatographic methods (Ans. 5---6; FF 8).
Examiner is correct in asserting that those of ordinary skill in this art
recognize that a combination of chromatographic techniques may be used to
purify proteins (FF 8). Examiner may also be correct in asserting that the
steps involved in developing a particular chromatographic methodology may
be similar across the field of chromatography (see FF 6). Examiner,
however, failed to establish an evidentiary basis on this record to support a
conclusion that a person of ordinary skill in this art would have looked to
(1) hydrophobic-interaction or (2) ion-exchange chromatography to obtain
an elution protocol for use in hydroxyapatite chromatography that required
"the elution buffer [to] comprise[] a constant concentration of phosphate" as
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required by Appellants' claim 1 (see Ans. 5---6; FF 9-10; cf Br. 13; FF 5;
Appellants' claim 1 ).
For the foregoing reasons, Examiner failed to establish that the
general conditions of a claim are disclosed in the prior art (cf Ans. 6).
Therefore, we are not persuaded by Examiner's assertion that Appellants'
claimed invention is simply the optimization of the methodology suggested
by the prior art (id.; cf Br. 13).
Claims 65--80 and 165:8
The method of Appellants' claim 65 requires, inter alia, contacting a
sample, comprising antibody monomers and high molecular weight
aggregates, with a hydroxyapatite resin under conditions, wherein the high
molecular weight aggregates are allowed "to bind more tightly than the
antibody monomers and, as loading continues, allowing the high molecular
weight aggregates to displace bound antibody monomers" (Appellants'
claim 65). Appellants' claims 66-80 and 165 depend directly or indirectly
from Appellants' claim 65.
Examiner failed to establish an evidentiary basis on this record to
support a conclusion that the combination of Gagnon, Giovannini, Kennedy,
and Williams suggests a method comprising, inter alia, contacting a sample,
comprising antibody monomers and high molecular weight aggregates, with
a hydroxyapatite resin under conditions, wherein the high molecular weight
aggregates are allowed "to bind more tightly than the antibody monomers
and, as loading continues, allowing the high molecular weight aggregates to
8 We note that claim 165 depends from canceled claim 129. For the
purposes of this appeal, we interpret claim 165 as depending from claim 65.
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Application 10/958,595
displace bound antibody monomers," as is required by Appellants' claim 65
(see Br. 15-16; cf Ans. 3---6).
Claims 166--169 and 171-178:
The method of Appellants' claim 166 comprises, inter alia, the step of
"eluting at least one antibody from [a hydroxyapatite resin] with at least one
elution buffer, wherein the elution buffer comprises about 3 mM to about 5
mM of a high ionic strength phosphate and about 0.2 M to about 2.5 M
NaCl" (see Appellants' claim 166). Appellants' claims 167-169 and 171-
178 depend directly or indirectly from Appellants' claim 166.
Examiner makes clear that Gagnon suggests sample and resin
equilibration buffers (FF 11 ). Examiner fails to identify a disclosure in
Gagnon of an elution buffer meeting the requirements of Appellants' claim
166. Examiner further fails to identify a disclosure in Giovannini that
suggests an elution buffer comprising, inter alia, 3 mM to about 5 mM of
high ionic strength phosphate (see Appellants' claim 166). Instead,
Examiner finds that Giovannini suggests an elution buffer comprising 20mM
sodium phosphate (FF 12). Examiner fails to establish an evidentiary basis
on this record to support a conclusion that a person of ordinary skill in this
art would have looked to the hydrophobic-interaction chromatography and
ion-exchange chromatography methods of Kennedy and Williams
respectively, to modify the sodium phosphate concentrations of an elution
buffer used in hydroxyapatite chromatography as suggested by the
combination of Gagnon and Giovannini (see Ans. 5---6 and 10; cf FF 9-10;
Br. 17-18).
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Application 10/958,595
Claims 179-192:
The method of Appellants' claim 1 79 comprises, inter alia, the elution
of "at least one antibody monomer from [a hydroxyapatite resin] with at
least one elution buffer, wherein the elution buffer comprises about 1 mM to
about 20 mM of a high ionic strength phosphate and about 0.2 M to about
2.5 M NaCl" (Appellants' claim 179). Claims 180-192 depend directly or
indirect! y from claim 179.
We recognize, but are not persuaded by, Examiner's reliance on
Giovannini to suggest the elution of an antibody from a hydroxyapatite resin
with a buffer comprising a phosphate concentration of about 20-30 mM
(Ans. 5 and 9; cf FF 12). Examiner fails to establish an evidentiary basis on
this record to support a conclusion that the combination of Gagnon,
Kennedy, and Williams makes up for the deficiency in Examiner's reliance
on Giovannini.
The combination of Gagnon, Giovannini, Kennedy, Williams, and Basi:
Based on the combination of Gagnon, Giovannini, Kennedy,
Williams, and Basi, Examiner concludes that, at the time Appellants'
invention was made, it would have been prima facie obvious "to employ the
antibody purification method using hydroxyapatite chromatography taught
by Gagnon, Kennedy and Williams []with the anti-Abeta antibody taught
by" Basi (Ans. 7).
Examiner relies on Basi to suggest an anti-Abeta antibody (FF 14).
Examiner failed to establish that Basi makes up for the deficiencies in the
combination of Gagnon, Giovannini, Kennedy, and Williams discussed
above (see generally Br. 21-23).
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Application 10/958,595
CONCLUSION OF LAW
The preponderance of evidence relied upon by Examiner fails to
support a conclusion of obviousness.
The rejection of claims 1-7, 12-14, 65-73, 78-80, 164--169, 171, 172,
177-186, and 190-192 under 35 U.S.C. § 103(a) as unpatentable over the
combination of Gagnon, Giovannini, Kennedy, and Williams is reversed.
The rejection of claims 8-11, 74--77, 173-176, and 187-189 under 35
U.S.C. § 103(a) as unpatentable over the combination of Gagnon,
Giovannini, Kennedy, Williams, and Basi is reversed.
REVERSED
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