Ex Parte Carpenter et al

Board of Patent Appeals and Interferences

Jul 24, 2012

10271832 (B.P.A.I. Jul. 24, 2012)

UNITED STATES PATENT AND TRADEMARKOFFICE
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.
10/271,832 10/16/2002 John F. Carpenter 42830-00247 9883
13586 7590 07/24/2012
Endo Pharmaceuticals Inc. c/o Marsh Fischmann &
Breyfogle LLP
8055 East Tufts Avenue, Suite 450
Denver, CO 80237
EXAMINER
GUPTA, ANISH
ART UNIT PAPER NUMBER
1654
MAIL DATE DELIVERY MODE
07/24/2012 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.
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
__________

BEFORE THE BOARD OF PATENT APPEALS
AND INTERFERENCES
__________

Ex parte JOHN F. CARPENTER, JEFFREY B. ETTER, and
ADRIAN C. SAMANIEGO
__________

Appeal 2011-010470
Application 10/271,832
Technology Center 1600
__________

Before DEMETRA J. MILLS, ERIC GRIMES, 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 product. The Examiner has rejected the claims as
anticipated and lacking adequate description in the Specification. We have
jurisdiction under 35 U.S.C. § 6(b). We reverse.
STATEMENT OF THE CASE
The Specification discloses that “stable concentrated protein
formulations can be prepared without requiring lyophilization. The
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concentrated protein formulation is a mixture of the protein in precipitated
form and a liquid medium, typically an aqueous medium.” (Spec. 2: 27-30.)
The concentrated formulations are prepared by “precipitation of a protein of
interest from a solution . . . with a suitable precipitating agent; followed by
removal of sufficient liquid from the resulting mixture to prepare a
concentrated mixture comprising . . . preferably at least 10 weight percent of
the precipitated protein” (id. at 3: 12-16). Suitable precipitating agents
include polyoxyalkylene block copolymers (id. at 9: 15-16).
Claims 2-24, 54, 56-61, and 82-107 are on appeal. Claim 23 is
representative and reads as follows:
23. A pharmaceutical product, comprising a pharmaceutical
composition contained within a sealed container, wherein:
the pharmaceutical composition comprises:
(i) polyoxyalkylene block copolymer;
(ii) at least 10 weight percent, relative to weight of the
pharmaceutical composition, of a precipitated protein, the precipitated
protein being in the form of a precipitate having been prepared by
precipitation from an aqueous liquid solution with the
polyoxyalkylene block copolymer; and
(iii) at least 10 weight percent, relative to the weight of the
pharmaceutical composition, water.

The claims stand rejected as follows:
• Claims 2-23, 54, 56-61, and 82-107 under 35 U.S.C. § 112, first
paragraph, for lack of adequate written description (Answer 3) and
• Claims 2, 4-11, 13, 14, 16-24, 54, 56-61, 83-85, 87-95, and 97-105
under 35 U.S.C. § 102(b) as anticipated by Kwak1 (Answer 7).

1 Kwak et al., U.S. Patent 5,861,158, Jan. 19, 1999.
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I.
The Examiner has rejected all of the claims on appeal except claim 24
for lack of adequate written description, on the basis that the Specification
does not describe the structural characteristics that allow a protein to be
precipitated with a polymer precipitating agent (Answer 5). The Examiner
cites Stratton2 as evidence that “[n]ot all peptides of greater than 15 Kda
form[ ] a precipitate in an aqueous liquid solution with the biocompatible
polymer precipitating agent and the precipitate is at least 10% by weight”
(id.). The Examiner also finds that “the claims are open to any polymer
material” but the Specification does not describe “what structural attributes
the polymer must contain to effectively precipitate the protein” (id. at 6).
Appellants argue that the claims are not directed to new chemical
substances, but to “a mixture including known ingredients, with one
ingredient being a protein-polyoxyalkylene block copolymer precipitate, and
with the mixture being highly concentrated in that precipitate ingredient”
(Appeal Br. 8). Appellants argue that one of skill in the art would recognize
that they were in possession of the full scope of the claimed invention based
on the Specification’s description (id. at 10-15). With regard to the
Examiner’s finding that the Specification does not adequately describe the
polymer in the claimed composition, Appellants argue that “all of the claims
rejected for lack of written description specifically require that the polymer
is a polyoxyalkylene block copolymer” (id. at 16).

2 Stratton et al., Drug Delivery Matrix Containing Native Protein
Precipitates Suspended in a Poloxamer Gel, 86 J. PHARM. SCI. 1006-1010
(1997).
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“[T]he examiner bears the initial burden, on review of the prior art or
on any other ground, of presenting a prima facie case of unpatentability.” In
re Oetiker, 977 F.2d 1443, 1445 (Fed. Cir. 1992). With respect to the
written description requirement of 35 U.S.C. § 112, first paragraph, “the test
for sufficiency is whether the disclosure of the application relied upon
reasonably conveys to those skilled in the art that the inventor had
possession of the claimed subject matter as of the filing date.” Ariad
Pharms., Inc. v. Eli Lilly & Co., 598 F.3d 1336, 1351 (Fed. Cir. 2010) (en
banc).
We agree with Appellants that the Examiner has not carried the
burden of showing that a person of ordinary skill in the art would not have
considered the Specification’s description to show that Appellants were in
possession of the claimed invention. The Specification describes a “method
of preparing pharmaceutical compositions including a protein” (Spec. 3: 8-
9):
[T]he method involves precipitation of a protein of interest
from a solution in which the protein is dissolved by contacting
the solution with a suitable precipitating agent; followed by
removal of sufficient liquid from the resulting mixture to
prepare a concentrated mixture comprising at least 8 weight
percent of the precipitated protein, and preferably at least 10
weight percent of the precipitated protein.
(Id. at 3: 12-16.) See also id. at 13, ll. 3-13 (“During the liquid separation
[step], sufficient liquid is removed to provide the desired concentration of
the precipitated protein in the concentrated mixture.”).
The Specification states that “[i]t is not . . . necessary that the protein
be highly concentrated in the solution” prior to precipitation (id. at 6: 10).
“Rather, it is generally preferred that the concentration of the protein in the
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solution is relatively low, for ease of preparation and handling of the
solution during processing” (id. at 6: 11-12). The Specification states that
the “protein used with the method of the present invention can be any
protein for which a highly concentrated formula is desired” (id. at 6: 17-18).
Thus, the Specification describes a composition resulting from a
process in which a protein in solution is mixed with a precipitating agent
such as a polyoxyalkylene block copolymer, and then liquid is removed
from the precipitated protein/polymer mixture until the desired protein
concentration is reached. The Specification states that the process can be
practiced with any desired protein, and does not state that the protein must
have any particular structural characteristics to make it appropriate for
inclusion in the claimed composition.
The Examiner cites no persuasive evidence to show that structure of a
protein affects its ability to be concentrated to at least 10% by weight as a
polymer/protein precipitate. The Examiner finds that “Stratton et al. teaches
a formulation of chymotrypsin with poloxamer 407 which did not produce a
precipitate of at least 10% by weight[]” (Answer 5). However, the Examiner
has not pointed to any specific disclosure in Stratton that shows a failed
attempt to make a composition comprising containing at least 10% protein in
a protein/polymer precipitate. Stratton describes making a protein
suspension of α-chymotrypsin and poloxamer 407 in which the final protein
concentration was 20mg/mL (Stratton 1006-1007). The Examiner has not,
however, pointed to any disclosure in Stratton of a liquid separation step
such as that described in the Specification as necessary to concentrate the
protein/polymer precipitate to a desired concentration. Thus, Stratton does
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not provide evidence that casts doubt on the Specification’s statement that
the claimed compositions can be made with any desired protein, regardless
of its structural characteristics.
With regard to the Examiner’s finding that the claims also lack
adequate description because they “are open to any polymer material”
(Answer 6), we agree with Appellants that all of the claims rejected on this
basis are limited to a polyoxyalkylene block copolymer. The Examiner has
not provided any persuasive basis for finding that a skilled worker would not
recognize, based on the Specification’s description, that Appellants are in
possession of a composition comprising a polyoxyalkylene block copolymer.
In summary, the Examiner has not provided an adequate basis for
finding that the claims on appeal lack adequate written description in the
Specification. We therefore reverse the rejection of claims 2-23, 54, 56-61,
and 82-107 under 35 U.S.C. § 112, first paragraph.
II.
The Examiner has rejected claims 2, 4-11, 13, 14, 16-24, 54, 56-61,
83-85, 87-95, and 97-105 as anticipated by Kwak (Answer 7). The
Examiner finds that Kwak discloses “a polymeric formulation compris[ing]
2.5% pluronic L121, tween 80 and phosphate buffered saline (see col. 6,
lines 56-65) is mixed with myeloma IgG (see col. 7)” (id. at 7-8). The
Examiner acknowledges that Kwak does not describe the mixture as forming
a precipitate, but finds that “such a result would be inherent in light of the
claims” (id. at 8). The Examiner also finds that the protein content recited in
the claims would be inherent in Kwak’s mixture, reasoning as follows:
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The claims do not recite a specific concentration of the polymer
nor a specific concentration for the peptide. The claims only
state that the protein precipitates when mixed with the a [sic]
biocompatible polymer precipitating agent. IgG has a molecular
weight of greater than 15kD. Thus, when the protein is mixed
with pluronic L121, a precipitate of at least 10%-99% would
inherently be achieved.
(Id.)
Appellants argue that, among other deficiencies, the composition in
Kwak that the Examiner finds to be anticipatory contains a protein
concentration that is much lower than the 10% by weight that is required by
the claims (Appeal Br. 29-33).
We agree with Appellants that the Examiner has not made a prima
facie case that Kwak identically disclose the claimed invention. The
Examiner relies on Kwak’s disclosure of a composition comprising, among
other things, 2.5% pluronic L121 and myeloma IgG (Answer 7-8, citing
Kwak at cols. 6-7). Pluronic L121 is described in the Specification as a
polyoxyalkylene block copolymer that is suitable for use as a precipitating
agent (Spec. 9: 30 to 10: 13). Kwak therefore describes a composition
containing a protein and a polyoxyalkylene block copolymer. However, the
claims require a composition comprising at least 10 weight percent of
precipitated protein (see, e.g., claim 23).
The Examiner points to the composition described in Kwak at
columns 6 to 7. That composition contains one milliliter of an adjuvant
containing Tween-80, Pluronic L121, and squalane in phosphate buffered
saline (see Kwak, col. 6, l. 57 to col. 7, l. 3) and one milliliter of a solution
of myeloma idiotype protein conjugated to keyhole limpet hemocyanin (“Id-
KLH”) (id. at col. 7, ll. 3-6). One milliliter of the Id-KLH solution “yielded
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a patient dose of 0.5 mg of Id” (id. at col. 6, ll. 54-55). Thus, the
composition cited by the Examiner as anticipatory contained approximately
1 mg of Id-KLH conjugate (assuming that the conjugate contains equal parts
Id and KLH) in a volume of 2 mL, or a protein concentration of about 0.5
mg/mL.
As Appellants have argued, the protein concentration in Kwak’s
composition is far below what is required by the claims, since 10% by
weight would correspond to approximately 100 mg/mL in Kwak’s water-
based composition (since one milliliter of water weighs one gram, or 1000
mg). The Examiner has pointed to no disclosure of a liquid separation step
in Kwak, like the step described in the instant Specification as necessary to
concentrate a protein/polymer precipitate to a desired concentration. Thus,
the Examiner has not made a prima facie showing that Kwak expressly or
inherently discloses a composition that meets all of the limitations of the
claims on appeal. The rejection of claims 2, 4-11, 13, 14, 16-24, 54, 56-61,
83-85, 87-95, and 97-105 as anticipated by Kwak is therefore reversed.
SUMMARY
We reverse the rejection of claims 2-23, 54, 56-61, and 82-107 for
lack of adequate written description and the rejection of claims 2, 4-11, 13,
14, 16-24, 54, 56-61, 83-85, 87-95, and 97-105 as anticipated by Kwak.

REVERSED

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