Ex Parte Hunt

Patent Trial and Appeal Board

Jul 15, 2013

11499432 (P.T.A.B. Jul. 15, 2013)

UNITED STATES PATENT AND TRADEMARK OFFICE
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
APPLICATION NO. FILING DATE FIRST NAMED INVENTOR ATTORNEY DOCKET NO. CONFIRMATION NO.
11/499,432 08/04/2006 Terrence J. Hunt 17319-CIP5 (BOT) 2872
7590 07/15/2013
Stephen Donovan
Allergan, Inc.
2525 Dupont Drive
Irvine, CA 92612
EXAMINER
FORD, VANESSA L
ART UNIT PAPER NUMBER
1646
MAIL DATE DELIVERY MODE
07/15/2013 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.
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
__________

BEFORE THE PATENT TRIAL AND APPEAL BOARD
__________

Ex parte TERRENCE J. HUNT
__________

Appeal 2012-002568
Application 11/499,432
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
botulinum toxin composition. The Examiner has rejected the claims as
obvious. We have jurisdiction under 35 U.S.C. § 6(b). We affirm.
STATEMENT OF THE CASE
Claims 1-3, 6-11, 14-16, 37-40, 46, and 47 are on appeal. Claim 1 is
representative and reads as follows:
1. A pharmaceutical composition comprising a botulinum toxin and a
primary and a secondary stabilizer, wherein the primary stabilizer is a
nonpasteurized recombinant albumin and the secondary stabilizer is a
Appeal 2012-002568
Application 11/499,432

2
divalent metal cation, wherein the botulinum toxin is present as a botulinum
toxin complex.

Issue
The Examiner has rejected all of the claims on appeal under 35 U.S.C.
§ 103(a) as obvious in view of Johnson,1 Peters,2 Ballance3 and Petrus.4 The
Examiner finds that Johnson discloses pharmaceutical compositions
comprising botulinum toxin and, among other things, albumin (Answer 5).
The Examiner finds that Johnson also discloses that the botulinum toxin can
be in the form of a botulinum toxin complex (id.).
The Examiner finds that, based on Peters, “the human serum albumin
used in the compositions of Johnson et al is considered ‘pasteurized’” (id.).
The Examiner finds that Ballance discloses “‘non-pasteurized’ recombinant
human serum albumin” (id. at 5), which Ballance discloses to have the
advantages of “lead[ing] to a purer product, better product consistency and
the elimination of bacterial or viral contamination” (id. at 6).
The Examiner finds that Petrus discloses “that zinc is a nontoxic metal
that has therapeutic functions … [and] teaches that zinc has anti-
inflammatory and anti-infective properties” (id.). The Examiner concludes
that it would have been obvious to substitute Ballance’s non-pasteurized
recombinant human serum albumin for the serum-derived human serum

1 Johnson et al., US 5,756,468, May 26, 1998.
2 Theodore Peters, Jr., ALL ABOUT ALBUMIN: BIOCHEMISTRY, GENETICS, AND
MEDICAL APPLICATIONS, Academic Press, San Diego, pp. 295-298 (1996).
3 D. J. Ballance, 34 ANÄ STHESIOL, INTENSIVMED. NOTFALLMED.
SCHMERZTHER 775-777 (1999).
4 Petrus, US 6,346,519 B1, Feb. 12, 2002.
Appeal 2012-002568
Application 11/499,432

3
albumin used by Johnson because “Ballance teaches that recombinant blood
products have advantages because they lead to a purer product, better
product consistency and the elimination of bacterial or viral contamination”
(id. at 8). The Examiner also concludes that it would have been obvious to
add zinc to the resulting composition “because Petrus teaches that zinc has a
stabilizing effect on cell membranes and inhibits the formation of free
radical[s] and has antimicrobial, antifungal and antiviral properties” (id.).
Appellant contends that the cited references would not have made
obvious the use of zinc as a stabilizer in a botulinum toxin composition
(Appeal Br. 6-8).
The issue presented is: Does the evidence of record support the
Examiner’s conclusion that the cited references would have made obvious a
pharmaceutical composition comprising botulinum toxin and zinc?
Findings of Fact
1. Johnson discloses a composition comprising botulinum toxin, a
thioalkyl compound, “a stabilizing protein, such as albumin,” and a
polysaccharide sugar (Johnson, col. 2:60-67).
2. Johnson discloses that the botulinum toxin may be in form of a
botulinum toxin complex (id. at col. 6, ll. 48-50).
3. Ballance discloses “a yeast-derived recombinant human albumin
product (RecombuminTM)” (Ballance 776, left col.).
4. Ballance’s production process for recombinant human albumin
does not include pasteurization (id.).
5. Ballance discloses that “one striking difference between
[recombinant and serum-derived human albumin] preparations was the
Appeal 2012-002568
Application 11/499,432

4
presence in serum-derived albumins of higher molecular weight polymeric
material, which forms during pasteurisation of the products. No such
denatured polymeric material was present in RecombuminTM rHA” (id. at
776, right col.).
6. Ballance discloses that “RecombuminTM recombinant human
albumin is a highly purified yeast-derived product which has been shown to
be structurally identical to serum-derived human albumin. As such, it
provides an alternative to HSA in the production of pharmaceutical
products.” (Id. at 776, right col.)
7. Petrus discloses that “[z]inc compounds have anti-inflammatory
and anti-infective properties” (id. at col. 6, ll. 7-8) and “are acknowledged as
… beneficial in wound healing, reducing inflammation, and ha[ve]
antimicrobial, antifungal and antiviral activity” (id. at col. 6, ll. 24-27).
8. Petrus discloses that “[z]inc stabilizes the cell membranes and
inhibits the formation of free radicals” (id. at col. 28-30).
9. 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.” (Id. at col. 2, ll. 9-16.)
Analysis
Claim 1 is directed to a pharmaceutical composition comprising a
botulinum toxin in the form of a toxin complex, nonpasteurized recombinant
albumin, and a divalent metal cation. Johnson discloses a botulinum toxin
composition comprising albumin, along with other components, and
discloses that the botulinum toxin may be in form of a botulinum toxin
Appeal 2012-002568
Application 11/499,432

5
complex. Ballance discloses recombinant human albumin, and discloses that
it differs from pasteurized serum-derived albumin by a lack of higher
molecular weight polymeric material. Ballance also discloses that its
recombinant product is “structurally identical to serum-derived human
albumin … [and] provides an alternative to HSA in the production of
pharmaceutical products” (FF 6). In view of these teachings, it would have
been obvious to substitute Ballance’s recombinant, non-pasteurized albumin
for the albumin in Johnson’s composition because Balance expressly
describes its product as an alternative to serum-derived HSA.
Petrus discloses that zinc compounds have several activities that
would be beneficial in therapeutic compositions, including anti-
inflammatory, antimicrobial, and antifungal activity, and inhibiting the
formation of free radicals (FF 8), which oxidize or damage otherwise
healthy cells (FF 9). In view of this disclosure, it would have been obvious
to modify Johnson’s composition to include zinc in order to confer on it the
therapeutically beneficial activities disclosed by Petrus.
Appellant argues that “Johnson does not disclose or suggest a
pharmaceutical composition comprising a botulinum toxin and a primary
and a secondary stabilizer, where the primary stabilizer is a non-pasteurized
recombinant albumin and the secondary stabilizer is a divalent metal cation,
and specifically where the botulinum toxin is present as a botulinum toxin
complex” (Appeal Br. 6).
This argument is not persuasive. The rejection is based on the
combined teachings of the cited references. The issue therefore is not
whether Johnson discloses all the limitations of claim 1, but whether those
Appeal 2012-002568
Application 11/499,432

6
limitations would have been obvious based on the disclosures of the cited
references taken together. See In re Gorman, 933 F.2d 982, 986 (Fed. Cir.
1991) (test of obviousness is “whether the teachings of the prior art, taken as
a whole, would have made obvious the claimed invention.”).
Appellant also argues that Petrus “does not disclose or suggest the use
of a divalent cation as a secondary stabilizer in combination with a
botulinum toxin and a primary stabilizer. Indeed, the reference fails to recite
‘divalent’ entirely.” (Appeal Br. 7). Appellant argues that Petrus does not
describe the use of zinc “in any protein-related context, and certainly not in
the context of protein stabilization” (id.).
These arguments are not persuasive. Zinc compounds provide zinc as
a divalent metal ion (see, e.g., claim 46 on appeal: “the divalent metal ion is
provided by a zinc ion source”). As recognized by the Examiner (Answer
14), Petrus discloses that zinc has anti-inflammatory, anti-microbial and
anti-fungal properties, and also inhibits the formation of free radicals. In
order to gain these benefits, one of ordinary skill in the art would have been
motivated to add zinc to the botulinum toxin composition made obvious by
Johnson and Ballance. Although the prior art may suggest adding zinc to a
botulinum toxin composition for a reason different from Appellant’s, “the
law does not require that the references be combined for the reasons
contemplated by the inventor.” In re Beattie, 974 F.2d 1309, 1312 (Fed. Cir.
1992).
The Examiner has also rejected independent claim 8 as obvious in
view of Johnson, Peters, Ballance and Petrus. Claim 8 is identical to claim
1, except that it further requires that “less than 9% of the recombinant
Appeal 2012-002568
Application 11/499,432

7
albumin is in an aggregate form.” Appellant argues that Johnson does not
disclose this limitation (Appeal Br. 6).
This argument is not persuasive because the Examiner’s rejection is
based on the combination of Johnson, Peters, Ballance and Petrus. Ballance
discloses that recombinant human albumin lacks the “higher molecular
weight polymeric material” (FF 5) – i.e., albumin in aggregate form – that is
seen in pasteurized albumin.
Thus, we affirm the rejection of independent claims 1 and 8.
Dependent claims 2, 3, 6, 7, 9-11, 14-16, 37-40, 46 and 47 have not been
argued separately and therefore fall with the independent claims. 37 C.F.R.
§ 41.37(c)(1)(iv).
Conclusion of Law
The evidence of record supports the Examiner’s conclusion that the
cited references would have made obvious the claimed pharmaceutical
composition comprising botulinum toxin and a divalent metal cation.
SUMMARY
We affirm the rejection of claims 1-3, 6-11, 14-16, 37-40, 46 and 47
under 35 U.S.C. § 103(a).
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

lp