Ex Parte Carlino

Board of Patent Appeals and Interferences

Nov 29, 2010

10523657 (B.P.A.I. Nov. 29, 2010)

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.
10/523,657 02/04/2005 Stefano Carlino LABM-10 9578
52450 7590 11/30/2010
KRIEG DEVAULT LLP
ONE INDIANA SQUARE
SUITE 2800
INDIANAPOLIS, IN 46204-2079
EXAMINER
PESELEV, ELLI
ART UNIT PAPER NUMBER
1623
MAIL DATE DELIVERY MODE
11/30/2010 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 STEFANO CARLINO
__________

Appeal 2010-008871
Application 10/523,657
Technology Center 1600
__________

Before LORA M. GREEN, FRANCISCO C. PRATS, and
JEFFREY N. FREDMAN, Administrative Patent Judges.

GREEN, Administrative Patent Judge.

DECISION ON APPEAL1
This is a decision on appeal under 35 U.S.C. § 134 from the
Examiner’s rejection of claims 1 and 4-9. 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
Claim 1 is the only independent claim on appeal, and reads as follows:
1. A process for preparing a sterile ready-to-use aqueous pharmaceutical
formulation comprising a high molecular weight hyaluronic acid salt (HA) at
a specified concentration, comprising the steps of:
- providing an aqueous formulation comprising high molecular weight
HA at a concentration of less than the specified concentration;
- passing said aqueous formulation through a filter having a pore size
less than 0.45 µm; and greater than 0.1 µm;
- concentrating said aqueous formulation by applying a vacuum and
boiling off water until said specified concentration is reached; and
- after the concentration step, filling the pharmaceutical formulation
directly into sterile recipients ready for pharmaceutical use, or into sterile
tanks and subsequently directly into sterile recipients ready for
pharmaceutical use.

The following grounds of rejection are before us for review:
I. Claims 1 and 4-9 stand rejected on the grounds of nonstatutory
obviousness-type double patenting as being unpatentable over
claims 1-23 of U.S. Patent No. 6,489,467 B1 to Carlino (issued
December 3, 2002) as combined with Perbellini (U.S. Patent No.
5,503,848, issued April 2, 1996).
II. Claims 1 and 4-9 stand rejected under 35 U.S.C. § 103(a) as being
rendered obvious by the combination of Carlino (U.S. Patent No.
6,489,467) or Carlino (WO 00/44925, published August 3, 2000)
and Perbellini.

We reverse.
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ISSUE
Has the Examiner established by a preponderance of the evidence that
the combination of claims 1-23 of U.S. Patent No. 6,489,467, Carlino (U.S.
Patent No. 6,489,467) or Carlino (WO 00/44925) with Perbellini renders the
method of independent claim 1 obvious?

FINDINGS OF FACT
FF1 The Specification teaches that the “invention relates to a process for
preparing a sterile high molecular weight hyaluronic acid salt as a final
formulation for pharmaceutical use.” (Spec. 1.)
FF2 The Specification notes:
Industrial extraction and purification processes of
hyaluronic acid typically produce hyaluronic acid salts, such as
sodium hyaluronate, in the form of a dried powder. The
purified pharmaceutical grade dried power may be used for
preparing, for example, aqueous pharmaceutical formulations
for the various pharmaceutical uses such as interarticular
injection, eye drops or vitreous humor replacement.
A common industrial process for preparing ready-to-use
pharmaceutical formulations comprises the mixing of a defined
quantity in weight of sodium hyaluronate with a precise volume
of water and, as the case may be, salt such as sodium chloride
and buffers such as phosphates and other excipients. As the
concentration and composition of the formulation for
pharmaceutical use should remain within a narrowly defined
range, the various components of the formulation are carefully
measured. The formulation is then filled into recipients such as
syringes and vials of defined dosages ready for use.
Subsequent to filling of the recipients, the formulation is
sterilized by autoclave typically at around 121º C for fifteen
minutes or more.

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(Spec. 2-3.)
FF3 According to the Specification:
During the concentrating step after filtration, the
concentration of HA may be monitored in real time in order to
stop the vacuum boiling when the specified concentration for
the ready-to-use pharmaceutical formulation is reached. The
monitoring or measuring process may advantageously be
carried out with a spectrophotometer with the sensing beam
placed in the formulation, the absorption of radiation in the
ultraviolet range (UV) being proportional to the HA
concentration. A particularly advantageous feature of this
invention is that it obviates the need to mix exact quantities of
water and hyaluronic acid to obtain the specified concentration
and ensure that such concentration is maintained through the
process. Instead, the initial HA and water mix has an
approximate concentration lower than the final formulation,
thus simplifying the process.

(Id. at 6-7 (emphasis added).)
FF4 The Examiner’s statement of the rejections may be found at pages 3-5
of the Answer.
FF5 The teaching and claims of U.S. Patent No. 6,489,467 are essentially
the same as the teachings of Carlino (WO 00/44925). We thus focus our
analysis on Carlino (WO 00/44925).
FF6 The Examiner finds that Carlino discloses “a process for preparing a
purified hyaluronic acid formulation comprising sterilizing hyaluronic acid
by passing an aqueous formulation through a filter having a pore size of 0.2
um.” (Ans. 5 (citing Carlino, p. 10).)
FF7 Carlino teaches a process of preparing a dry powder of hyaluronic
acid, wherein the an aqueous solution is filter sterilized, and concentrated
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using a filter having a 5,000-10,000 Daltons molecular weight cutoff.
(Carlino, p.10.)
FF8 The Examiner notes that Carlino does not disclose “the step of
concentrating said formulation under vacuum until a desired concentration is
achieved.” (Ans. 5.)
FF9 The Examiner finds that Perbellini discloses “preparation of a
hyaluronic acid formulation wherein said formulation is subjected to a
vacuum until a desired concentration is achieved and parceling said
formulation into a sterile containers.” (Id.)
FF10 Specifically, Perbellini teaches the following preparation process for
preparing a spongy material that consists of hyaluronic acid or its derivatives
and appears from a macroscopic point of view as a highly microporous
spongy little disk:
1. Dissolution of the active principle
In a suitable apparatus, equipped with a heating system,
suitable stirring and vacuum/nitrogen pressure/sterile filtrate
system, hyaluronic acid, or one of its estereal derivatives, is
dissolved in water for injectable preparations, so as to reach a
concentration ranging between 1 mg/ml and 40 mg/ml.
2. Solution filtration
The solution containing hyaluronic sodium salt is filtered
suitably through a sterilizing membrane, having a porosity of
0.2 micrometers, afterwards it is collected in a sterile
environment.
3. Solution distribution
The filtered solution is parcelled out in a sterile
environment, into suitable sterile containers, such as tiny
bottles, blisters and the like, by dosing the solution so as to
achieve 10 mg of active principle in each container.
4. Lyophilization
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The containers, after having been filled up, are put into a
lyophilization apparatus and the product is frozen to a
temperature ranging between 0º C. and -90º C.; the temperature
decrease for achieving the freezing is captied [sic] out at rates
ranging between 1º C. every 20 seconds and 1º C. every 3
hours.
Drying step by high vacuum (residual vacuum in the
chamber ranging between 1000 and 1Hg mm) and heating step
with plate temperature ranging between -90º C. and +60º C.,
follow.
* * * *
At the end of the lyophilization the tiny bottles are
stoppered in a sterile way.

(Perbellini, col. 10, ll. 21-57.)
FF11 Thus, Perbellini, while teaching a step of vacuum filtration, as well as
a step of lyophilization, does not teach a step of concentrating an aqueous
solution of HA by applying a vacuum and boiling off water until a more
concentrated aqueous solution of HA is obtained.
FF12 The Examiner concludes it would gave been obvious to use the
process of Perbellini in the process of Carlino “in order to achieve a
formulation which is suitable to the [sic, be] parceled out into sterile
containers.” (Ans. 5.)

PRINCIPLES OF LAW
If the claim preamble, when read in the context of the entire
claim, recites limitations of the claim, or, if the preamble is
“necessary to give life, meaning, and vitality” to the claim, then
the claim preamble should be construed as if in the balance of
the claim. . . . If, however, the body of the claim fully and
intrinsically sets forth the complete invention, including all of
its limitations, and the preamble offers no distinct definition of
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any of the the claimed invention’s limitations, but rather merely
states, for example, the purpose of intended use of the
invention, then the preamble is of no significance to claim
construction because it cannot be said to constitute or explain a
claim limitation.

Pitney Bowes, Inc. v. Hewlett Packard Co., 182 F.3d 1298, 1305 (Fed. Cir.
1999). Moreover, while limitations from the Specification are not to be read
into the claim, “[i]t is entirely proper to use the specification to interpret
what . . . [is] meant by a word or a phrase in the claim.” E.I. du Pont de
Nemours & Co. v. Phillips Petroleum Co., 849 F.2d 1430, 1433 (Fed. Cir.
1988). See also In re Morris, 127 F.3d 1048, 1054 (Fed. Cir. 1997).
In addition, the Examiner must consider all of the claim limitations in
setting forth a rejection over the prior art. See, e.g., In re Geerdes, 491 F.2d
1260, 1262-63 (CCPA 1974) (in considering grounds of rejection, “every
limitation in the claim must be given effect rather than considering one in
isolation from the others.”).

ANALYSIS
We start with claim interpretation. Claim 1 is drawn to a “process for
preparing a sterile ready-to-use aqueous pharmaceutical formulation
comprising a high molecular weight hyaluronic acid salt (HA) at a specified
concentration,” wherein an aqueous formulation of HA is concentrated
under vacuum by boiling off water, and then after the concentration step,
“filling the pharmaceutical formulation directly into sterile recipients ready
for pharmaceutical use, or into sterile tanks and subsequently directly into
sterile recipients ready for pharmaceutical use.” In light of the teachings of
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the Specification, we interpret the process of claim 1 as requiring the HA to
be always in an aqueous solution. Stated in other terms, we interpret the
claim as excluding a step of concentrating the HA by drying the HA to a
powder and adding back water.
Appellant argues that Perbellini “does not disclose any step for
concentration of a filter-sterilized solution of HA, by applying a vacuum and
boiling off water until a specified concentration is reached, as required by
the claims of the present invention.” (App. Br. 15.) We agree. As noted
above, Perbellini’s process involves preparing an HA solution from a dried
product, which the claims exclude (See FF10 and 11.) As the Examiner’s
fact-finding is incorrect, and in view of the claim interpretation set forth
above, we are compelled to reverse the rejections on appeal.

CONCLUSION OF LAW
We conclude that the Examiner has not established by a
preponderance of the evidence that the combination of claims 1-23 of U.S.
Patent No. 6,489,467, Carlino (U.S. Patent No. 6,489,467) or Carlino (WO
00/44925) with Perbellini renders the method of independent claim 1
obvious. We are thus compelled to reverse both rejections on appeal.

REVERSED

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cdc

KRIEG DEVAULT LLP
ONE INDIANA SQUARE
SUITE 2800
INDIANAPOLIS, IN 46204-2079