Ex Parte Mahler et al

Board of Patent Appeals and Interferences

Nov 8, 2010

10996597 (B.P.A.I. Nov. 8, 2010)

UNITED STATES PATENT AND TRADEMARK OFFICE
__________

BEFORE THE BOARD OF PATENT APPEALS
AND INTERFERENCES
__________

Ex parte HANNS-CHRISTIAN MAHLER and ROBERT MUELLER
__________

Appeal 2010-003089
Application 10/996,597
Technology Center 1600
__________

Before EDWARD C. KIMLIN, PETER F. KRATZ, and
FRANCISCO C. PRATS, Administrative Patent Judges.

PRATS, Administrative Patent Judge.

DECISION ON APPEAL1
This appeal under 35 U.S.C. § 134 involves claims to an aqueous
antibody-containing composition. The Examiner entered a rejection for
obviousness, and also entered a provisional rejection for obviousness-type
double patenting. We have jurisdiction under 35 U.S.C. § 6(b).

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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STATEMENT OF THE CASE
Claims 1-8, 10-15, 17-24, 26, and 27 are pending and on appeal (App.
Br. 2). Claims 1 and 27 are representative and read as follows:
Claim 1. An aqueous preparation comprising an anti-EGFR
antibody, a buffer, an amino acid and a surfactant, said preparation
having been stored for at least 8 weeks without having been
lyophilized.

Claim 27. An aqueous preparation consisting essentially of a
solvent, which is at least partially water, an anti-EGFR antibody, a
buffer, an amino acid, a surfactant, and an isotonicity modifier
comprising sodium chloride, said preparation not having been
lyophilized.

The Examiner rejected the claims as follows:
(1) Claims 1-8, 10-15, 17-24, 26, and 27, rejected under 35 U.S.C. §
103(a) as obvious over Mahler2 et al. and Lam3 et al. (Ans. 3-4); and
(2) Claims 1-8, 10-15, 17-24, 26, and 27, provisionally rejected for
nonstatutory obviousness-type double patenting over claims 12-15 of
copending Application No. 10/499,569 in view of Lam (Ans. 5-6).
We affirm the obviousness rejection.
However, the application that formed the basis for the provisional
double patenting rejection has been abandoned.4 The provisional rejection is
therefore moot, and we will not address it.

2 U.S. Patent Application Pub. No. 2004/0170632 A1 (filed June 18, 2002).
3 U.S. Patent No. 6,171,586 B1 (filed June 12, 1998).
4 Our review of the electronic file for copending application 10/499,569
shows the last entry as being a Notice of Abandonment entered on August
26, 2008.
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OBVIOUSNESS
ISSUE
The Examiner cited Mahler as disclosing a stabilized pharmaceutical
composition containing an antibody encompassed by claim 1, and cited Lam
as disclosing an aqueous antibody-stabilizing composition that contains
buffers, amino acids, and surfactants, as recited in claim 1, and also contains
sodium chloride as a tonicifier, as recited in claim 27 (Ans. 3-4).
The Examiner concluded that an ordinary artisan would have
considered it obvious to use Lam’s composition to further stabilize Mahler’s
antibody preparation (id. at 4). The Examiner reasoned that the artisan
“would have been motivated to do so with a reasonable expectation of
success by teachings in Lam et al. and Mahler et al. for increased stability of
an aqueous preparation of an antibody suitable for therapeutic use” (id.).
Appellants do not argue that the claimed compositions have any
unexpected properties, or that the claimed methods provide any unexpected
results (see App. Br. 5-7). Appellants instead argue that, for a number of
reasons, the Examiner failed to make out a prima facie case of obviousness
(id.).
In view of Appellants’ arguments, we select claims 1 and 27 as
representative of the rejected claims. See 37 C.F.R. § 41.37(c)(1)(vii).
Thus, given the positions advanced by Appellants and the Examiner,
the issue is whether the evidence of record supports the Examiner’s position
that an ordinary artisan would have considered the preparations recited in
claims 1 and 27 prima facie obvious in view of Mahler and Lam.

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FINDINGS OF FACT (“FF”)
1. Mahler discloses “a stable liquid pharmaceutical formulation
comprising Cetuximab®, a chimeric monoclonal antibody against the
receptor of endothelial growth factor (EGF receptor). The formulation has
increased storage stability and can be used parenterally for the treatment of
tumours” (Mahler, abstract).
2. In a preferred embodiment, Mahler’s liquid preparation contains the
antibody, as well as “a phosphate buffer in the range from about pH 6 to
about pH 8, a polyoxyethylene sorbitan fatty acid ester and an isotonic agent
in a concentration necessary for establishing isotonicity. The formulation
preferably comprises sodium chloride as isotonic agent” (id. at [0017]).
3. Mahler discloses:
If Cetuximab® is in the form of a solid, for example in the form
of a lyophilisate, the formulation according to the invention can
be prepared by firstly dissolving Cetuximab® in water or an
aqueous solution comprising one or more of the further
constituents, and subsequently adding the amounts necessary in
each case of stock solutions comprising the further constituents,
the further constituents in solid form and/or water.

(Id. at [0019].)
4. Lam discloses “a stable aqueous pharmaceutical formulation
comprising a therapeutically effective amount of an antibody not subjected
to prior lyophiliz[ati]on, 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).
5. Lam discloses that, “[p]referably the formulation is stable at a
temperature of about 2-8° C. for at least one year, and/or is stable at a
temperature of about 30° C. for at least one month and/or is stable following
freezing and thawing of the formulation” (id. at col. 2, ll. 29-33).
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6. Lam discloses that suitable buffers for its composition “include
acetate (e.g. sodium acetate), succinate (such as sodium succinate),
gluconate, histidine, citrate and other organic acid buffers. Where a freeze-
thaw stable formulation is desired, the buffer is preferably not phosphate”
(id. at col. 6, l. 67, through col. 7, l. 3).
7. Lam discloses that its composition can include antioxidants “including
ascorbic acid and methionine” (id. at col. 23, ll. 10-11).
8. Lam discloses that the polyol in its compositions “acts as a tonicifier
and may stabilize the antibody . . . . In preferred embodiments, the
formulation does not contain a tonicifying amount of a salt such as sodium
chloride, as this may cause the antibody to precipitate and/or may result in
oxidation at low pH” (id. at col. 22, ll. 31-36).
PRINCIPLES OF LAW
In KSR Int’l Co. v. Teleflex Inc., 550 U.S. 398 (2007), the Supreme
Court reaffirmed that “when a patent ‘simply arranges old elements with
each performing the same function it had been known to perform’ and yields
no more than one would expect from such an arrangement, the combination
is obvious.” Id. at 417 (quoting Sakraida v. Ag Pro, Inc., 425 U.S. 273, 282
(1976)).
The Court also reaffirmed that, “[i]n determining whether the subject
matter of a patent claim is obvious, neither the particular motivation nor the
avowed purpose of the patentee controls. What matters is the objective
reach of the claim. If the claim extends to what is obvious, it is invalid
under § 103.” Id. at 419.
Also, “in a section 103 inquiry, ‘the fact that a specific [embodiment]
is taught to be preferred is not controlling, since all disclosures of the prior
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art, including unpreferred embodiments, must be considered.’” Merck &
Co., Inc. v. Biocraft Laboratories, Inc., 874 F.2d 804, 807 (Fed. Cir. 1989)
(quoting In re Lamberti, 545 F.2d 747, 750 (CCPA 1976).
ANALYSIS
Appellants’ arguments do not persuade us that the Examiner failed to
make a prima facie case of obviousness with respect to claims 1 and 27.
Claim 1 recites an aqueous preparation comprising an anti-EGFR
antibody, a buffer, an amino acid and a surfactant, the preparation having
been stored for at least 8 weeks without having been lyophilized. We agree
with the Examiner that an ordinary artisan, advised by Mahler that it was
desirable to provide the antibody in the form of a storage-stable preparation
(FF 1), and further advised that Lam’s composition allowed storage of
antibodies for up to one year without lyophilization (FF 4-5), would have
been prompted to use Lam’s composition to render Mahler’s antibody
storage stable.
We acknowledge Mahler’s disclosure that the antibody can be
included in storage-stable preparations after being lyophilized (FF 3).
However, Appellants do not point to, and we do not see, any teachings in
Mahler requiring the antibody to be lyophilized before included in storage-
stable formulations.
To the contrary, given Lam’s explicit disclosure that antibodies can be
rendered storage-stable for up to one year using its formulation (FF 5), we
agree with the Examiner that an ordinary artisan would have considered it
obvious to used Lam’s formulation, which undisputedly contains the
ingredients recited in claim 1, to stabilize Mahler’s antibody. Moreover,
given Lam’s disclosure that its formulation allows storage for up to one year
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without lyophilization (FF 4-5), we are not persuaded that the cited
references fail to suggest claim 1’s feature requiring the preparation to be
stored for at least 8 weeks without having been lyophilized.
We also acknowledge that Lam uses a polyol in its stabilization
solution (FF 4). However, because claim 1 recites its preparation using open
“comprising” language, claim 1 does not exclude additional unrecited
ingredients. See Genentech, Inc. v. Chiron Corp., 112 F.3d 495, 501 (Fed.
Cir. 1997) (“‘Comprising’ is a term of art used in claim language which
means that the named elements are essential, but other elements may be
added and still form a construct within the scope of the claim.”).
Claim 1 is therefore not distinguishable from the preparation
suggested by Mahler and Lam based on Lam’s suggestion that the
preparation should contain additional ingredients.
Similarly, the fact that Lam might have added histidine (FF 6) and
methionine (FF 7) to the formulation for different reasons than Appellants
does not render Lam’s teachings any less suggestive of including those
amino acids in the composition. See KSR, 550 U.S. at 419.
We also acknowledge that Mahler uses phosphate buffer in its
storage-stable compositions (FF 2), whereas Lam discloses that “[w]here a
freeze-thaw stable formulation is desired, the buffer is preferably not
phosphate” (Lam, col. 7, ll. 2-3; FF 6).
However, even assuming for argument’s sake that Mahler considers
phosphate buffer to be a requirement for its compositions, Mahler is relied
on in combination with Lam, which explicitly states that buffers other than
phosphate are useful for rendering antibodies storage-stable for extended
periods (FF 6). We are therefore not persuaded that an ordinary artisan
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lacked impetus for using Lam’s formulation to stabilize and store Mahler’s
antibody.
In sum, Appellants’ arguments do not persuade us that the Examiner
failed to make a prima facie case of obviousness with respect to claim 1.
Accordingly, we affirm the Examiner’s rejection of that claim, as well as
claims 2-8, 10-15, 17-24, and 26, which were not argued separately.
Claim 27 recites “[a]n aqueous preparation consisting essentially of a
solvent, which is at least partially water, an anti-EGFR antibody, a buffer, an
amino acid, a surfactant, and an isotonicity modifier comprising sodium
chloride, said preparation not having been lyophilized.”
Appellants’ entire argument regarding claim 27 states: “[w]ith respect
to claim 27, neither reference teaches an aqueous preparation consisting
essentially of a solvent that is at least partially water, along with an anti-
EGFR antibody, a buffer, an amino acid, a surfactant, and an isotonicity
modifier comprising sodium chloride, which has not been lyophilized” (App.
Br. 7). We are not persuaded.
As discussed above, we agree with the Examiner that an ordinary
artisan would have been prompted to use Lam’s formulation, which contains
water, a buffer, amino acid, and a surfactant to stabilize and store Mahler’s
antibody without lyophilization. We acknowledge Lam’s disclosure that
sodium chloride is not the preferred tonicifying agent for low pH
preparations (FF 8).
However, it is well settled that the prior art must be considered for all
its teachings, including unpreferred embodiments. See Merck v. Biocraft,
874 F.2d at 807. Moreover, Appellants point to no evidence of record
controverting the Examiner’s finding (Ans. 4) that an ordinary artisan would
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have considered sodium chloride to be a useful tonicifying agent in view of
Lam’s teachings.
We also acknowledge that claim 27 requires the preparation to
“‘consist[] essentially of’” the claimed ingredients. However, that language
excludes only those additional ingredients that affect the basic and novel
properties of the invention. See PPG Indus. v. Guardian Indus. Corp, 156
F.3d 1351, 1354 (Fed. Cir. 1998).
Appellants point to no evidence suggesting that any of the unclaimed
ingredients in the formulations of either reference would affect the basic and
novel properties of the preparation recited in claim 27. Accordingly, we also
affirm the Examiner’s obviousness rejection of claim 27.

SUMMARY
We affirm the Examiner’s rejection of claims 1-8, 10-15, 17-24, 26,
and 27 under 35 U.S.C. § 103(a) as obvious over Mahler and Lam.
However, because the allegedly conflicting application has been
abandoned, we do not address the Examiner’s provisional rejection of claims
1-8, 10-15, 17-24, 26, and 27 for nonstatutory obviousness-type double
patenting.

TIME PERIOD
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

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