Ex Parte Hunt

Board of Patent Appeals and Interferences

Aug 20, 2012

12498293 (B.P.A.I. Aug. 20, 2012)

UNITED STATES PATENT AND TRADEMARK OFFICE
__________

BEFORE THE BOARD OF PATENT APPEALS
AND INTERFERENCES
__________

Ex parte TERRENCE J. HUNT
__________

Appeal 2011-011852
Application 12/498,293
Technology Center 1600
__________

Before ERIC GRIMES, LORA M. GREEN, and
MELANIE L. McCOLLUM, Administrative Patent Judges.

GRIMES, Administrative Patent Judge.

DECISION ON APPEAL
This is an appeal under 35 U.S.C. § 134 involving claims to a
pharmaceutical composition, which the Examiner has rejected for
obviousness. We have jurisdiction under 35 U.S.C. § 6(b). We affirm.
STATEMENT OF THE CASE
Claims 1-7, 9, 11-17, 19, and 20 are on appeal. The claims have not
been argued separately and therefore stand or fall together. 37 C.F.R.
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§ 41.37(c)(1)(vii). Claims 1, 11, and 17, the only independent claims, read
as follows:
1. A pharmaceutical composition, comprising
(a) a botulinum toxin;
(b) N-acetyl-tryptophan (NAT);
(c) zinc;
(d) caprylate;
(e) recombinant human serum albumin (rHSA);
(f) polysorbate 80; and
(g) sodium chloride.

11. A pharmaceutical composition, comprising
(a) a botulinum toxin;
(b) a tryptophan;
(c) a recombinant albumin (rA), and sodium chloride, wherein
the pharmaceutical composition exhibits an enhanced potency.

17. A pharmaceutical composition, comprising:
(a) a botulinum toxin;
(b) caprylate;
(c) recombinant human serum albumin (rHSA), and;
(d) polysorbate 80 (P80) and sodium chloride, wherein the
botulinum toxin present in the pharmaceutical composition is
stabilized.

The Examiner has rejected all of the claims on appeal under 35 U.S.C.
§ 103(a) as obvious based on Moyer,
1
Fleer,
2
Grangeorge,
3
and Petrus
4

(Answer 4). The Examiner finds that Moyer discloses “pharmaceutical
compositions comprising botulinum toxin, 0.5 mg/mL of human serum

1
Moyer et al., WO 00/15245, Mar. 23, 2000
2
Fleer et al., EP O,0361991, Apr. 4, 1990
3
Grangeorge et al., US 5,118,794, June2, 1992
4
Petrus, US 6,346,519 B, Feb. 12, 2002
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albumin (first excipient) and 100 mM of sodium chloride (second
excipient)” but does not teach recombinant albumin (id. at 5). The Examiner
finds that Fleer discloses recombinant human serum albumin (HSA), and
teaches that it “has improved purity and better stability without viral
contamination” (id.).
The Examiner finds that Grangeorge discloses “that N-acetyl-
trytophan [sic] and sodium caprylate are used to stabilize[ ] human albumin
for therapeutic purposes” and that polysorbate 80 is used for the same
purpose (id. at 6). Finally, the Examiner finds that Petrus discloses that zinc
has therapeutic activity: “anti-inflammatory. . . antimicrobial, antifungal
and antiviral properties . . . a stabilizing effect on cell membranes and
inhibits the formation of free radicals” (id.).
The Examiner concludes that it would have been obvious to use
recombinant HSA in Moyer‟s pharmaceutical composition because of the
advantages disclosed by Fleer, that it would have been obvious to include N-
acetyl-tryptophan (NAT), caprylate, and polysorbate 80 (P80) as stabilizers,
and to include zinc for the therapeutic functions disclosed by Petrus, and
therefore the claimed composition would have been obvious (id. at 8).
Appellants contend that the claimed combination would not have been
obvious because Moyer does not disclose recombinant albumin in its
formulation (Appeal Br. 8), and that, for this reason, the “cited references
cannot motivate one to produce the claimed compositions” (id. at 10) and
that Moyer in fact teaches away from the use of recombinant albumin for the
same reason (id.). Appellants also contend that the references do not
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provide a reasonable expectation of success in replacing the albumin of
Moyer with the recombinant version of Fleer (id. at 8).
The issue presented is: Does the evidence of record support the
Examiner‟s conclusion that a person of ordinary skill in the art would have
considered it obvious to combine the components required by claim 1, and
would have had a reasonable expectation of success in doing so?
Findings of Fact
1. Moyer discloses “therapeutic formulations of botulinum toxin”
(Moyer 1: 7-8).
2. Moyer exemplifies a formulation comprising botulinum toxin,
sodium chloride, and “Human albumin, FDA released” (id. at 10, Table 1).
3. Moyer claims a formulation comprising botulinum toxin and an
“excipient protein . . . selected from the group consisting of serum albumin,
recombinant human serum albumin, and gelatin” (id. at 30, ll. 19-20).
4. Fleer discloses that “[u]p to now, HSA is generally produced by
conventional techniques of fractionation of plasma derived from blood
donors” (Fleer 3: 4-5).
5. Fleer discloses that “genetic engineering . . . has opened up the
possibility of obtaining improved products of higher purity and better
stability without viral contamination (e.g. hepatitis B and AIDS) and at
lower cost” (id. at 3: 9-11).
6. Fleer discloses “genetically engineered, modified yeast strains . . .
which are capable of efficiently producing and excreting HSA in its native
conformation into the growth medium” (id. at 4: 29-31).
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7. Grangeorge discloses a “process for stabilizing human albumin
solutions for therapeutic use . . . comprising adding, in addition to the usual
stabilizing formula, a surface active agent selected from Tween 80
(polysorbate 80, the firm Atlas – oleate of polyoxyethylene sorbitan) . . . or
any other equivalent agent” (Grangeorge, col. 2, ll. 32-43).
8. Grangeorge states that “[u]sual stabilizing solution is intended to
mean in particular sodium caprylate, sodium acetyl tryptophanate, sodium
mandelate or a mixture of two or three thereof” (id. at col. 2, ll. 64-66).
9. Grangeorge discloses that the addition of a surface active agent
such as polysorbate 80 prevents the denaturing of the albumin and
consequent formation of insoluble particles during pasteurization (see id. at
col. 2, l. 67 to col. 3, l. 4).
10. Petrus discloses that “[z]inc compounds have anti-inflammatory
. . . properties” and “are . . . beneficial in wound healing, reducing
inflammation, and ha[ve] antimicrobial, antifungal and antiviral activity”
(Petrus, col. 6, ll. 8-9, 22-27).
11. Petrus discloses that “[z]inc stabilizes the cell membranes and
inhibits the formation of free radicals” (id. at col. 28-30).
12. Petrus discloses that “[f]ree radicals . . . oxidize or damage
otherwise healthy cells. They damage DNA, corrode cell membranes, and
may play a role in the development of cancer, heart and lung disease,
cataracts, and cause or accelerate the aging process.” (Petrus, col. 2, ll. 9-
16.)
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Analysis
Claim 1 is directed to a composition comprising a botulinum toxin
and six other components. Moyer discloses a composition comprising a
botulinum toxin and one of the other components (sodium chloride), as well
as human albumin (FF 2). Fleer discloses recombinant HSA, in its native
conformation, and discloses that it is more pure than non-recombinant HSA
and also eliminates the risk of viral contamination (FF 5, 6). We agree with
the Examiner that, based on Fleer, a person of ordinary skill in the art would
have considered it obvious to use recombinant HSA in Moyer‟s formulation.
Grangeorge discloses that sodium caprylate and N-acetyl-tryptophan
(or “sodium acetyl tryptophanate”) are part of the usual stabilizing solution
for human albumin (FF 8), and that adding polysorbate 80 to those agents
provides additional stabilization during heat treatment (FF 7, 9). Petrus
discloses that zinc has several activities that would be beneficial in
therapeutic compositions, including inhibiting the formation of free radicals
(FF 11), which oxidize or damage otherwise healthy cells (FF 12).
We agree with the Examiner that these disclosures would have made
it obvious to a person of ordinary skill in the art to include sodium caprylate,
N-acetyl-tryptophan, polysorbate 80, and zinc in the formulation made
obvious by Moyer and Fleer, in order to gain the benefits disclosed by
Grangeorge and Petrus. The cited references therefore support a prima facie
case of obviousness with respect to claim 1, as well as claims 11 and 17,
which require only subsets of the components required by claim 1.
Appellant argues it would not have been obvious to use recombinant
HSA in Moyer‟s formulation because “Moyer fails to mention „recombinant‟
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in connection with albumin entirely” and “does not teach the use of
recombinant albumins” (Appeal Br. 8). Appellant also argues that “[t]he
cited references cannot motivate one to produce the claimed compositions,
as the primary reference, Moyer, fails to suggest the use of recombinant
albumins” (id. at 10) and that, for the same reason, Moyer teaches away
from the use of recombinant albumin (id.).
This argument is unpersuasive. First, Moyer does in fact disclose
recombinant HSA in its formulation, by claiming a formulation comprising
botulinum toxin and an “excipient protein . . . selected from the group
consisting of . . . recombinant human serum albumin” (FF 3). Second, even
if Moyer had not mentioned recombinant HSA, its use would nonetheless
have been obvious to a person of ordinary skill in the art familiar with Fleer
and Moyer, because Fleer discloses that it is more pure than nonrecombinant
HSA and free of viral contamination.
Appellant also argues that Moyer and Fleer would not have provided a
reasonable expectation of success in using recombinant HSA in Moyer‟s
formulation (Appeal Br. 8-9). However, Fleer expressly states that its
recombinant HSA has the native conformation (FF 6); i.e., the same
conformation as HSA purified from human plasma. Appellant has not
provided persuasive evidence to show that a skilled worker would not
reasonably have expected Fleer‟s recombinant HSA to successfully
substitute for the “Human albumin, FDA released” in Moyer‟s exemplary
composition (FF 2).
With regard to Grangeorge and Petrus, Appellant concedes that “these
references do disclose the elements noted by the Office” (Appeal Br. 9), but
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argues that Grangeorge does not mention recombinant albumins (id.) and
that Petrus relates to compositions for treating arthritis and claims zinc
compounds as nitric oxide synthase inhibitors (id.)
These arguments are not persuasive. Fleer discloses that its
recombinant HSA has the same conformation as native HSA; thus, a person
of ordinary skill in the art would reasonably expect that the stabilizing
effects described by Grangeorge would apply to either type of HSA. In
addition, although Petrus claims a method of treating arthritis by
administering a nitric oxide synthase inhibitor, which can be a zinc
compound (see Petrus, col. 9, ll. 14-18; col. 10, ll. 10-11), it also discloses
that zinc has other activities, including some that would be expected to be
beneficial in a pharmaceutical composition comprising botulinum toxin.
Conclusion of Law
The evidence of record supports the Examiner‟s conclusion that a
person of ordinary skill in the art would have considered it obvious to
combine, with a reasonable expectation of success, the components required
by claim 1. Claims 2-7, 9, 11-17, 19, and 20 fall with claim 1. 37 C.F.R.
§ 41.37(c)(1)(vii).
SUMMARY
We affirm the rejection of claims 1-7, 9, 11-17, 19, and 20 under 35
U.S.C. § 103(a).
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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

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