Ex Parte Manning et al

Board of Patent Appeals and Interferences

Jun 8, 2012

10683214 (B.P.A.I. Jun. 8, 2012)

MOD PTOL-90A (Rev.06/08)

APPLICATION NO./
CONTROL NO.
FILING DATE FIRST NAMED INVENTOR /
PATENT IN REEXAMINATION
ATTORNEY DOCKET NO.
10/683,214 10/07/2003 Manning, Mark C.

EXAMINER
King & Spalding LLP
P.O. Box 889
Belmont, CA 94002-0889
Seharaseyon, Jegatheesan
ART UNIT PAPER NUMBER
1646
MAIL DATE DELIVERY MODE

06/11/2012 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.

UNITED STATES DEPARTMENT OF COMMERCE
U.S. Patent and Trademark Office
Address : COMMISSIONER FOR PATENTS
P.O. Box 1450
Alexandria, Virginia 22313-1450
www.uspto.gov
UNITED STATES PATENT AND TRADEMARK OFFICE
_____________________________________________________________________________________
UNITED STATES PATENT AND TRADEMARK OFFICE
__________

BEFORE THE BOARD OF PATENT APPEALS
AND INTERFERENCES
__________

Ex parte MARK C. MANNING and RAJIV NAYAR
__________

Appeal 2011-001298
Application 10/683,214
Technology Center 1600
__________

Before DONALD E. ADAMS, DEMETRA J. MILLS, and
FRANCISCO C. PRATS, Administrative Patent Judges.

PRATS, Administrative Patent Judge.

DECISION ON APPEAL
This appeal under 35 U.S.C. § 134 involves claims to a composition
that contains an interferon and histidine. The Examiner entered a rejection
for obviousness.
We have jurisdiction under 35 U.S.C. § 6(b). We affirm.
STATEMENT OF THE CASE
Claims 1, 11-14, and 29 stand rejected and appealed (App. Br. 4).
Claims 1 and 11 illustrate the appealed subject matter and read as follows:
1. A composition comprising, interferon-τ and histidine.
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11. The composition of claim 1, wherein said histidine is effective to
bind with said interferon-τ to stabilize its α-helical tertiary structure.

The sole rejection before us for review is the Examiner’s rejection of
claims 1, 11-14, and 29 under 35 U.S.C. § 103(a) as obvious over Bazer
1
and
Lee
2
(Ans. 3-4).
DISCUSSION
The Examiner found that Bazer described pharmaceutical
compositions that contained a protein recognized in the art as being
interferon-τ (Ans. 3-4). The Examiner conceded that Bazer did “not teach
compositions with histidine for stabilization purposes” (id. at 4).
To address that deficiency, the Examiner cited Lee as disclosing
“stabilized protein compositions comprising histidine” and reasoned that an
ordinary artisan would have considered it obvious to modify Bazer’s
compositions “with the addition of histidine as disclosed in Lee et al.
because, Lee et al. teach that the addition of histidine stabilize monomeric
proteins” (id. (citing Lee, col. 6, ll. 35-44)). The Examiner also reasoned
that an ordinary artisan would have had “a reasonable expectation of success
because Lee et al. has disclosed that protein [compositions] including
interferons are stabilized by the addition of amino acids” (id. (citing Lee,
cols. 2 and 3)).
As stated in In re Oetiker, 977 F.2d 1443, 1445 (Fed. Cir. 1992):
[T]he examiner bears the initial burden . . . of presenting a
prima facie case of unpatentability. . . .
After evidence or argument is submitted by the applicant
in response, patentability is determined on the totality of the

1
WO 90/09806 A2 (published September 7, 1990).
2
U.S. Patent No. 5,917, 021 (issued June 29, 1999).
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3
record, by a preponderance of evidence with due consideration
to persuasiveness of argument.

Appellants’ arguments do not persuade us that a preponderance of the
evidence fails to support the Examiner’s prima facie case of obviousness.
Regarding claim 1, we acknowledge, as Appellants argue, that Lee
discloses that “the art has recognized that different proteins exhibit highly
variable inactivation responses” (Lee, col. 2, ll. 42-43). It is well settled,
however, that “[o]bviousness does not require absolute predictability of
success. . . . For obviousness under § 103, all that is required is a reasonable
expectation of success.” In re O’Farrell, 853 F.2d 894, 903-04 (Fed. Cir.
1988); accord, In re Kubin, 561 F.3d 1351, 1359-61 (Fed. Cir. 2009).
Thus, as the Supreme Court explained in KSR Int’l Co. v. Teleflex
Inc., 550 U.S. 398, 417 (2007), “if a technique has been used to improve one
device, and a person of ordinary skill in the art would recognize that it would
improve similar devices in the same way, using the technique is obvious
unless its actual application is beyond his or her skill.”
In this case, as the Examiner pointed out, although Lee recognized the
highly variable nature of protein inactivation processes, Lee also disclosed
that a number of practitioners had found that including amino acids,
histidine among them, in therapeutic interferon-containing compositions
significantly improved the compositions’ storage stability (see Lee, col. 2, ll.
56-66; see also id. at col. 3, ll. 25-31 (“Patel . . . disclosed a method for
increasing the storage stability of an aqueous formulation containing a
protein component selected from among the group consisting of interferons .
. . by the addition of a stabilizing amount of methionine, histidine, or
mixtures thereof.”)). As Lee explains, “Patel reports that without such
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treatment, aqueous protein formulations typically have short useful storage
lives after reconstitution, even when stored at low temperatures (e.g., 5° C.)”
(id. at col. 3, ll. 31-34).
Thus, in addition to disclosing its own histidine-stabilized therapeutic
protein-containing compositions (see, e.g., id. at col. 6, ll. 37-51), Lee
discloses that similar results were known in the art, and were applicable to
interferons. We are therefore not persuaded that an ordinary artisan lacked a
reasonable expectation that histidine would be useful for stabilizing the
interferon-τ compositions described by Bazer (see Bazer 15-16).
Thus, as Appellants’ arguments do not persuade us that a
preponderance of the evidence fails to support the Examiner’s prima facie
case as to claim 1, we affirm the Examiner’s rejection of that claim as
obvious over Bazer and Lee. As they were argued in the same grouping,
claims 12-14 and 29 fall with claim 1.
As to claim 11, Appellants argue that the Patel
3
reference, which was
cited in Lee, shows that interferon-α is apparently stabilized equally well
using either histidine or methionine, whereas other proteins, including GM-
CSF and IL-4 are better stabilized with methionine as opposed to histidine
(App. Br. 10). In further contrast, Appellants urge, the data presented by co-
inventor Rajiv Nayar in a declaration
4
presented under 37 C.F.R. § 1.132
shows that histidine is significantly more effective in stabilizing interferon-τ
than methionine (id.; see also id. at Evidence Appendix).
Thus, Appellants argue, “[s]uch data provide evidence that one of skill
in the art could not predict the stabilizing effects of particular amino acids on

3
U.S. Patent No. 5,358,708 (issued October 25, 1994).
4
Nayar Declaration (executed January 22, 2008).
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5
interferon-τ” (App. Br. 10). Moreover, Appellants urge, given that claim 11
broadly encompasses interferon-τ proteins with amino acid sequences that
are relatively similar to interferon-α sequences, encompassing as many as 55
amino acid substitutions in the interferon-τ sequence, and also “[g]iven the
accepted unpredictability of the biotechnological arts, especially with respect
to polypeptide structure and function,” an ordinary artisan “could not have
predicted that histidine would impart significant stability of secondary and
tertiary structure of interferon-τ” (id. at 11).
Further, Appellants contend, given that the PTO “routinely rejects
claims drawn to genera of polypeptides having less than 90% homology to a
reference sequence, alleging unpredictability in the art and poor correlation
between protein structure and function,” it is inconsistent “to impute
characteristics of one polypeptide to another when the level of homology is
only 45-68%, particularly when the subject polypeptides (i.e., interferon-α
and interferon-τ) are known to exhibit different biological properties” (id. at
12).
We do not find these arguments persuasive, essentially for the reasons
discussed above as to claim 1. While it might be true that the art of
stabilizing therapeutic proteins was not absolutely predictable, we again note
that absolute predictability is not the criterion of obviousness. See In re
O’Farrell, 853 F.2d at 903-04; In re Kubin, 561 F.3d at 1359-61.
As noted above, Lee discloses not only that histidine was useful in
general for stabilizing monomeric proteins for storage purposes (see, e.g.,
Lee, col. 6, ll. 37-51), but also that histidine was useful for stabilizing
interferons (id. at col. 3, ll. 25-34), precisely the type of protein recited in
claim 11. Thus, regardless of any perceived inconsistency between the
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rejection at issue here and rejections that might have been made in other
cases, in the instant case the prior art cited by the Examiner would have
provided an ordinary artisan with ample impetus and expectation of success
for doing precisely what claim 11 requires – including histidine in a
composition comprising interferon-τ so as to stabilize the interferon’s
structure.
We acknowledge the data in the Nayar Declaration showing that
interferon-τ formulated with histidine “(a) is less prone to aggregation than
when formulated with methionine; (b) maintains its protein content to a
greater extent than when formulated with methionine; and (c) retains its
tertiary conformation to a greater degree than when formulated with
methionine” (Nayar Declaration 4). Rather than showing unpredictability,
however, the Nayar Declaration verifies precisely what the prior art suggests
– that histidine, the stabilizing agent recited in claim 11, acts to stabilize
interferons (see Lee, col. 3, ll. 25-34).
The fact that methionine might not function as well histidine in
stabilizing interferon-τ, whereas those amino acids provide similar
stabilization to interferon-α, simply verifies something Appellants concede
an ordinary artisan already knew – that proteins are not inactivated in a
consistent fashion (see, e.g., id. at col. 2, ll. 40-43). Indeed, while the Nayar
Declaration notes the differences in stabilization imparted to interferon-τ by
histidine and methionine, Appellants point to nothing in the Declaration
suggesting that an ordinary artisan would have considered that difference to
be unexpected.
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Thus, it is well settled that “any superior property must be unexpected
to be considered as evidence of non-obviousness.” Pfizer, Inc. v. Apotex,
Inc., 480 F.3d 1348, 1371 (Fed. Cir. 2007).
Moreover, “[m]ere improvement in properties does not always suffice
to show unexpected results. . . . [W]hen an applicant demonstrates
substantially improved results . . . and states that the results were
unexpected, this should suffice to establish unexpected results in the absence
of evidence to the contrary.” In re Soni, 54 F.3d 746, 751 (Fed. Cir. 1995).
Further, “when unexpected results are used as evidence of
nonobviousness, the results must be shown to be unexpected compared with
the closest prior art.” In re Baxter-Travenol Labs., 952 F.2d 388, 392 (Fed.
Cir. 1991).
Here, Appellants urge that “the Examiner has not given proper
consideration to the surprising and unpredictable finding that interferon-τ is
stabilized in the presence of histidine” (App. Br. 11). However, Appellants
point to no specific or direct comparative evidence between any prior art
composition and a composition encompassed by the claims showing that the
claimed composition has any property that an ordinary would have
considered unexpected in light of the cited references’ teachings.
Accordingly, as Appellants’ arguments do not persuade us that a
preponderance of the evidence fails to support the Examiner’s prima facie
case as to claim 11, and as Appellants have not advanced any specific
evidence adequate to undermine or rebut the Examiner’s prima facie case,
we affirm the Examiner’s rejection of claim 11 as obvious over Bazer and
Lee.

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Application 10/683,214

8
SUMMARY
We affirm the Examiner’s the Examiner’s obviousness rejection of
claims 1, 11-14, and 29 over Bazer and Lee.

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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