Ex Parte Cipolla et al

Patent Trial and Appeal Board

Sep 9, 2016

13036904 (P.T.A.B. Sep. 9, 2016)

UNITED STA TES p A TENT AND TRADEMARK OFFICE
APPLICATION NO. FILING DATE
13/036,904 02/28/2011
93726 7590 09/13/2016
EPA - Bozicevic Field & Francis LLP
Bozicevic, Field & Francis
1900 University Ave
Suite 200
East Palo Alto, CA 94303
FIRST NAMED INVENTOR
DAVID C. CIPOLLA
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
ATTORNEY DOCKET NO. CONFIRMATION NO.
AERX-126CIP2CON2 5839
EXAMINER
LONG, SCOTT
ART UNIT PAPER NUMBER
1633
NOTIFICATION DATE DELIVERY MODE
09/13/2016 ELECTRONIC
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.
Notice of the Office communication was sent electronically on above-indicated "Notification Date" to the
following e-mail address( es):
docket@bozpat.com
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
BEFORE THE PATENT TRIAL AND APPEAL BOARD
Ex parte DAVID C. CIPOLLA and JAMES BLANCHARD
Appeal2015-000761
Application 13/036,9041
Technology Center 1600
Before FRANCISCO C. PRATS, JEFFREY N. FREDMAN, and
RYAN H. FLAX, Administrative Patent Judges.
FLAX, Administrative Patent Judge.
DECISION ON APPEAL
This is a decision on appeal under 35 U.S.C. § 134(a) involving
claims directed to a pharmaceutical formulation. Claims 52, 55-58, 60, and
63-67 are on appeal as rejected under 35 U.S.C. § 103(a). We have
jurisdiction under 35 U.S.C. § 6(b).
We reverse.
STATEMENT OF THE CASE
The appealed claims can be found in the Claims Appendix of the
Appeal Brief. Claim 52 is the sole independent claim, is representative, and
reads as follows:
1 The Real Party in Interest is Aradigm Corporation. App. Br. 2.
Appeal2015-000761
Application 13/036,904
52. A pharmaceutical formulation, comprising:
a pharmaceutically acceptable carrier for aerosolized delivery to
human lungs, the carrier comprising sodium acetate in a solution;
and
a free, unencapsulated ciprofloxacin dissolved at a concentration
of 10 mg/ml or more;
wherein the formulation has a pH of 4.0 or less.
App. Br. 20 (Claims App'x).
The following rejections are on appeal:
Claims 52, 55-58, 60, 66, and 67 rejected under 35 U.S.C. §103(a)
over Majumdar.2 Final Action 5.
Claims 63-65 rejected under 35 U.S.C. § 103(a) over Majumdar and
Fleischer. 3 Final Action 7.
DISCUSSION
We address the obviousness rejections together because the same
determinative facts and arguments apply to each.
The Examiner concluded that the claims were obvious over Majumdar
alone or in combination with Fleisher, but relied primarily on the disclosure
of the first reference. Looking to page 2809 of Majumdar, the Examiner
determined that the reference disclosed:
2 Sadhana Majumdar et al., Efficacies of Liposome-Encapsulated
Streptomycin and Ciprojloxacin against Mycobacterium avium-M.
intracellulare Complex Infections in Human Peripheral Blood
Monocyte/Macrophages, 36 ANTIMICROB. AGENTS CHEMOTHER. 2808-15
(1992) (hereinafter "Majumdar").
3 European Patent Application Pub. No. EP 1 083 886B1 (published Apr. 2,
2003) (hereinafter "Fleisher").
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Application 13/036,904
'Ciprofloxacin was encapsulated in multilamellar vesicles
composed of phosphatidylglycerol-phosphatidylcholine-
cholesterol (molar ratio, 1 :9:5) ... solutions of antibiotic at 25
mg/ml were prepared in either (i) unbuffered water, (ii) 40 mM
glycine buffer at pH 3.5, or (iii) 10 mM acetate buffer at pH 5.6
... unencapsulated drug was eliminated by repeated (three times)
centrifugation.' . . . Therefore, before the repeated (three times)
centrifugation and washing, the liposomal ciprofloxacin
composition of Majumdar also contained free unencapsulated
ciprofloxacin. Furthermore, Majumdar et al. indicated that the
' [a ]mount of encapsulated ciprofloxacin was determined by
measuring . . . in a Perkin Elmer Lambda 4 B spectrophotometer
by using a calibration curve made with 1 to 25 µg of
ciprofloxacin per ml.'
Final Action 9-10.4 Majumdar does not support the Examiner's conclusion.
"In rejecting claims under 35 U.S.C. § 103, the examiner bears the
initial burden of presenting a prima facie case of obviousness. Only if that
burden is met, does the burden of coming forward with evidence or
argument shift to the applicant." In re Rijckaert, 9 F.3d 1531, 1532 (Fed.
Cir. 1993). "The Patent Office has the initial duty of supplying the factual
basis for its rejection. It may not ... resort to speculation, unfounded
assumptions or hindsight reconstruction to supply deficiencies" in the cited
references. In re Warner, 379 F.2d 1011, 1017 (CCPA 1967). The evidence
of record does not provide an adequate factual basis for the Examiner's
prima facie case for obviousness. The Examiner does not identify
persuasive evidence showing that Majumdar alone, or in combination with
4 The Examiner cited Fleischer for alleged disclosure of aerosolizable
formulations and encapsulation of drug. Final Action 13.
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Application 13/036,904
Fleisher, discloses, teaches, or suggests each limitation of claim 52 as
combined in the claim.
The claims recite the pharmaceutically acceptable carrier for the free,
encapsulated ciprofloxacin comprises "sodium acetate." In the Reply Brief,
Appellants note:
In Majumdar et al. on page 2809, col. 2 in the first full paragraph
the second sentence from the end reads as follows:
"It was found to be important to avoid use of NaCl to
adjust the osmolality, since ciprofloxacin precipitated in
the presence of this salt."
This clearly teaches one skilled in the art away from applicants'
invention.
Reply Br. 11, 25. As to the inclusion of sodium ions (with acetate) and the
claim element "sodium acetate," we agree. Majumdar does disclose an
intermediate solution comprising ciprofloxacin diluted in NaCl, KCl, and
acetate at a pH of 5 .6. er Final Action. 7 (discussing relevant portion of
Majumdar as suggesting sodium acetate). Regarding this intermediate
formulation step, Majumdar teaches that the drug-containing solution is
"diluted 30-fold," thus, even if the solution did contain some sodium acetate,
at this point it would not have the concentration of ciprofloxacin recited by
the claims. Moreover, in addition to veering away from the recited drug
concentration, at this point, the intermediate drug formulation of Majumdar
is also taught to have a pH higher than that recited by the claims. Cf Final
Action 8 (discussing modifying pH). As to the intermediate solutions
containing ciprofloxacin concentrations encompassed by claim 52, given
Majumdar's express avoidance of NaCl (Majumdar 2809, right col.), the
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Application 13/036,904
Examiner does not persuade us that a skilled artisan would have used
sodium acetate as the buffer component.
The claims recite the pharmaceutical formulation includes "free,
unencapsulated ciprofloxacin." See claim 52, supra. Majumdar discloses a
series of solutions, which, at one point, contain free, unencapsulated
ciprofloxacin, but never in combination with all the other elements recited
by the claims, e.g., with sodium acetate, at a concentration of 10 mg/ml, at a
pH of 4.0 or less. See Majumdar 2809, right col. To arrive at such a
formulation the Examiner has mixed and matched components from
different intermediate/final formulations. Final Action 5-9. Moreover, the
point of Majumdar is to formulate a pharmaceutical with encapsulated drug
and, in the process of describing fabricating such a pharmaceutical, the
authors teach "[t]he unencapsulated drug was eliminated." Id.
The claims recite ciprofloxacin is "dissolved at a concentration of 10
mg/ml or more." See claim 52, supra. The Examiner does not direct us to
any evidence on the record showing persuasively that the drug would be
present at such a concentration in a formulation with the other elements
recited by the claims (or suggesting that it should be). The spectrometry
data cited by the Examiner does not support such a determination-it
indicates only "[t]he amount of encapsulated ciprofloxacin," not the
presence or amount of any unencapsulated drug, as that was eliminated in
prior formulation steps. Majumdar 2809, right col.
The claims recite "the formulation has a pH of 4.0 or less." See claim
52, supra. While the Examiner has argued that Majumdar suggests adjusting
a Cipro formulation's pH (several different pHs are disclosed), the Examiner
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Application 13/036,904
does not persuade us that a formulation including unencapsulated
ciprofloxacin at 10 mg/ml, and sodium acetate, at a pH of 4.0 or less is
taught or suggested by Majumdar. The intermediate formulation disclosed
by Majumdar that comprises both unencapsulated drug and acetate buffer is
disclosed as having a pH of 5.6. The Examiner does not direct us to a
persuasive teaching, in the reference or generally in the art, suggesting that
acetate could or should be used at the pH (3.5) achieved using a different
buffer (glycine).
Thus, for the reasons discussed above, the Examiner does not
persuade us that Majumdar provides adequate reason or suggestion to mix
and match the features of its distinct and separate intermediate and/or final
formulations to arrive at the claimed formulation. Therefore, for these
reasons, we find that the evidence of record does not support the Examiner's
determination that the claims would have been obvious over the cited prior
art combination. We reverse each obviousness rejection.
SUMMARY
The rejection of claims 52, 55-58, 60, 66, and 67 under 35 U.S.C.
§ 103(a) over Majumdar is reversed.
The rejection of claims 63-65 under 35 U.S.C. § 103(a) over
Majumdar and Fleischer is reversed.
REVERSED
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