Ex Parte Murthy

Patent Trial and Appeal Board

Sep 16, 2013

12210566 (P.T.A.B. Sep. 16, 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.
12/210,566 09/15/2008 Yerramilli V.S.N. MURTHY 47624.101 6822
27683 7590 09/16/2013
HAYNES AND BOONE, LLP
IP Section
2323 Victory Avenue
Suite 700
Dallas, TX 75219
EXAMINER
CLAYTOR, DEIRDRE RENEE
ART UNIT PAPER NUMBER
1627
MAIL DATE DELIVERY MODE
09/16/2013 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 YERRAMILLI V.S.N. MURTHY
__________

Appeal 2012-002267
Application 12/210,566
Technology Center 1600
__________

Before JEFFREY N. FREDMAN, ERICA A. FRANKLIN and
ANNETTE R. REIMERS, Administrative Patent Judges.

FREDMAN, Administrative Patent Judge.

DECISION ON APPEAL
This is an appeal1 under 35 U.S.C. § 134 involving claims to a
pharmaceutical composition comprising fluoroquinolones. The Examiner
rejected the claims as obvious. We have jurisdiction under 35 U.S.C. § 6(b).
We reverse.

1 Appellant identifies the Real Party in Interest as IDEXX
Laboratories Inc. (see App. Br. 3).
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Statement of the Case
Background
“The fluoroquinolone class of antibiotics are a powerful tool in
combating bacterial infections” (Spec. 2 ¶ 0009). “[L]iquid oral
pharmaceutical compositions, such as solutions and suspensions, are
desirable because they are easier to administer. Fluoroquinolones, however,
are difficult to dissolve in liquids. Accordingly, there is a need in the art for
new liquid fluoroquinolone compositions that can be more easily
administered to animals” (Spec. 4 ¶ 0018).
The Claims
Claims 1-5, 7, 8, 11-18, 20-34, 46, and 47 are on appeal. Claim 1 is
representative and reads as follows:
1. A pharmaceutical composition comprising:
(i) a fluoroquinolone;
(ii) a salt formed between a carboxylate anion and a
divalent metal cation; and
(iii) a liquid comprising an organic solvent selected
from the group consisting of glycerol, propylene glycol,
glycerol formal, and mixtures thereof.

The issues
A. The Examiner rejected claims 1-5, 7, 8, 11-18, 20-28, 30, 31, 33, 46,
and 47 under 35 U.S.C. § 103(a) as obvious over Al-Razzak2 and Purwar3
(Ans. 4-6).

2 Al-Razzak et al., US 5,334,589, issued Aug. 2, 1994.
3 Purwar et al., US 5,843,930, issued Dec. 1, 1998.
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B. The Examiner rejected claims 1-5, 7, 8, 11-18, 20-28, 30, 31, 33, 46,
and 47 under 35 U.S.C. § 103(a) as obvious over Purwar and Park4 (Ans. 6-
8).
C. The Examiner rejected claims 29, 32, and 34 under 35 U.S.C. § 103(a)
as obvious over Al-Razzak, Purwar, Park, and Nakar5 (Ans. 8-9).
A. 35 U.S.C. § 103(a) as obvious over Al-Razzak and Purwar
The Examiner finds that “Al-Razzak et al. teach pharmaceutical
compositions comprised of salt complexes of a quinolone carboxylic acid”
(Ans. 5). The Examiner finds that Al-Razzak teaches “[s]uitable metal ions
include magnesium, which is the preferred metal ion (Col. 3, lines 40-50).
The compositions include physiologically acceptable carriers which include
polyols and water for parenteral administration” (Ans. 5).
The Examiner finds that Al-Razzak “does not teach glycerol as the
organic solvent” (Ans. 5). The Examiner finds that Purwar teaches
“compositions comprised of ciprofloxacin, a fluoroquinolone, glycerin
(glycerol), and sodium acetate and acetic acid” (Ans. 5). The Examiner
finds that “glycerin is added to augment the viscosity of the aqueous solution
and water sufficient to produce a liquid composition” (Ans. 5).
The Examiner finds it obvious “to formulate the liquid composition in
forms such as those that are injectable in an effort to systemically treat
bacterial infections” (Ans. 5). The Examiner further finds it obvious “to

4 Park et al., Ionization and Divalent Cation Complexation of
Quinolone Antibiotics in Aqueous Solution, 21 BULL. KOREAN
CHEM. SOC. 849-854 (2000).
5 Nakar, D., WO 2004/035071 A1, published Apr. 29, 2004.
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combine the teachings in an effort to increase the biological activity of
ciprofloxacin as an antibacterial agent” (Ans. 6).
The issue with respect to this rejection is: Does the evidence of record
support the Examiner’s conclusion that Al-Razzak and Purwar render claim
1 obvious?
Findings of Fact
The following findings of fact (“FF”) are supported by a
preponderance of the evidence of record.
1. Al-Razzak teaches “compositions of a quinolone carboxylic
acid, such as temafloxacin, that are useful for oral or parenteral
administration to a human or veterinary patient” (Al-Razzak, col. 2, ll. 36-
39).
2. Al-Razzak teaches “compositions comprising a salt complex of
a quinolone carboxylic acid in stable solution with a pharmaceutically
acceptable carrier” (Al-Razzak, col. 3, ll. 9-11).
3. Al-Razzak teaches that “[e]xamples of quinolone carboxylic
acids which may benefit from formulation in a composition of the invention
include temafloxacin, ciprofloxacin, norfloxacin, sarafloxacin, and
difloxacin” (Al-Razzak, col. 3, ll. 20-23).
4. Al-Razzak teaches that:
Metal ions suitable for use in the present invention include
those which are capable of forming the above complexes
and which are physiologically tolerated at the concentrations
necessary to produce an effective dose of the quinolone
carboxylic acid being administered. Examples include
divalent metal ions such as magnesium

(Al-Razzak, col. 3, ll. 40-46).
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5. Al-Razzak teaches that “[i]llustrative carriers for parenteral
administration include . . . vehicles such as alcohols, polyols ” (Al-Razzak,
col. 3, l. 65 to col. 4, l. 1).
6. Purwar teaches a composition comprising “ciprofloxacin in an
amount effective for anti-bacterial action; methylcellulose in an amount
effective for augmenting the viscosity of the composition to a viscosity
greater than that of water; potassium sorbate in an amount effective as a
preservative against contamination by microorganisms; sodium acetate and
acetic acid” (Purwar, col. 2, ll. 61-66).
7. Purwar teaches adding “glycerin in an effective amount to
adjust the tonicity of the composition from about 200 to about 600
milliosmoles, that is, to provide a composition which is approximately
isotonic” (Purwar, col. 3, ll. 6-9).
8. Purwar teaches that
glycerine augments the viscosity of the aqueous solution to a
viscosity greater than that of water. The composition
comprises: ciprofloxacin in an amount effective for
antibacterial action; glycerine in an amount effective for
augmenting the viscosity of the composition to a viscosity
greater than that of water; and water sufficient to produce a
liquid composition.

(Purwar, col. 3, ll. 42-48).
9. Lecomte6 teaches that “MICs should reflect both the uptake in
the cell and the activities of quinolones on the DNA gyrase. As expected, the

6 Lecomte et al., Effect of Magnesium Complexation by
Fluoroquinolones on Their Antibacterial Properties, 38
ANTIMICROBIAL AGENTS CHEMOTHERAPY 2810-2816 (1994).
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addition of magnesium increased the MICs, depending on the strain and the
drug” (Lecomte 2814, col. 2).
10. Kozjek7 teaches that “[c]oncomitant administration of
ciprofloxacin (CPX) or other fluoroquinolones and drugs containing metals
resulted in diminished absorption of fluoroquinolones” (Kozjek 109).
Principles of Law
“In proceedings before the Patent and Trademark Office, the
Examiner bears the burden of establishing a prima facie case of obviousness
based upon the prior art.” In re Fritch, 972 F.2d 1260, 1265 (Fed. Cir. 1992).
Analysis
The Examiner finds it obvious to combine the compositions of Al-
Razzak and Purwar “in an effort to increase the biological activity of
ciprofloxacin as an antibacterial agent” (Ans. 6).
Appellant contends that if “the carboxylate anion of the claimed
invention is replaced with an inorganic anion (for example, chloride, if HCl
was used as the acid), the improved solubility of the fluoroquinolone without
compromising oral bioavailability would not be observed . . . There is no
suggestion in Al-Razzak of the criticality of using a carboxylic acid” (App.
Br. 8). Appellant contends that “one of ordinary skill in the art would have
expected that a composition containing both a fluoroquinolone and a
divalent metal ion would have reduced activity because the presence of the
divalent metal cation results in reduced oral bioavailability of the

7 Kozjek et al., Pharmacokinetics of ciprofloxacin metal
complexes, 46 ACT. PHARM. 109-114 (1996).
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fluoroquinolone and poorer uptake of the fluoroquinolone by bacterial cells”
(App. Br. 10).
We find that Appellant has the better position. Claim 1 requires the
presence of both a fluoroquinolone and of a carboxylate anion, where the
carboxylate anion is defined by the Specification (see Spec. 8 ¶ 0036).
While Purwar teaches incorporation of acetate (FF 6), a carboxylate anion
(Spec. 12 ¶ 0089), Appellant’s cited art teaches that the ordinary artisan
would not select a divalent metal cation for use in a fluroquinolone
composition. Lecomte teaches that “addition of magnesium increased the
MICs, depending on the strain and the drug” (Lecomte 2814, col. 2; FF 9).
That is, magnesium reduced the effectiveness of the antibiotic by increasing
the minimum inhibitory concentration to require more antibiotic to inhibit
the bacterial growth. Further Kozjek teaches that “[c]oncomitant
administration of ciprofloxacin (CPX) or other fluoroquinolones and drugs
containing metals resulted in diminished absorption of fluoroquinolones”
(Kozjek 109; FF 10). Thus, when the art is considered as a whole, we agree
with Appellant that the ordinary artisan would not have found it obvious to
incorporate the carboxylate anion of Purwar with a divalent metal cation and
fluoroquinolone of Al-Razzak since the combination would have been
expected to inhibit the activity and uptake of the fluoroquinolone antibiotic
(FF 9-10).
Conclusion of Law
The evidence of record does not support the Examiner’s conclusion
that Al-Razzak and Purwar render claim 1 obvious.

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B. 35 U.S.C. § 103(a) as obvious over Purwar and Park
The Examiner finds it obvious to “combine the teachings of Purwar et
al., which teach pharmaceutical compositions comprised of ciprofloxacin,
glycerol and water, with the teachings of Park et al. which teach that
quinolone antibiotics form complexes with divalent cations to play important
biological roles” (Ans. 7).
The issue with respect to this rejection is: Does the evidence of record
support the Examiner’s conclusion that Purwar and Park render claim 1
obvious?
Findings of Fact
11. Park teaches “that quinolone antibiotics can form complexes
with divalent cations. This chelation of certain metal ions between the
carbonyl and carboxyl groups of these molecules plays an important
biological role” (Park 849, col. 2).
12. Park teaches that “[w]hen Mg2+ is added to an achievable
urinary concentration (5.6 mM), the activity of these antibiotics is reduced
for virtually every pH tested, but the antagonistic action of Mg2+ on two
groups of drugs, with and without the piperazinyl group, does not exhibit a
similar pH dependence” (Park 850, col. 1).
13. Park teaches the “formation constants with some divalent
cations are measured for OFL, NOR and FLU in pH 75 buffer solution. In
this pH, OFL and NOR exist mainly as zwitterion, but FLU as anion.23
Table 3 lists the formation constants of each antibiotics with several divalent
cations” (Park 852, col. 2).

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Analysis
We agree with Appellant that “the references cited by Park that the
complexation with divalent cations plays a biological role (i. e., references 1,
2, and 7) do not disclose or suggest that a divalent cation should be
combined with a fluoroquinolone. Rather, the prior art teaches to avoid such
a combination, especially when considering bioavailability, a primary
concern when formulating a pharmaceutical composition” (App. Br. 14).
Indeed, the Park reference itself teaches that the addition of
magnesium to the fluoroquinolone antibiotics reduces their activity at
virtually every pH (FF 12). Here, Park discourages the claimed solution by
teaching that the use of magnesium will reduce the activity and uptake of the
antibiotic. See In re Fulton, 391 F.3d 1195, 1201 (Fed. Cir. 2004).
Conclusion of Law
The evidence of record does not support the Examiner’s conclusion
that Purwar and Park render claim 1 obvious.
C. 35 U.S.C. § 103(a) as obvious over Al-Razzak, Purwar, Park, and
Nakar
This rejection relies upon the underlying obviousness rejections
relying upon Al-Razzak, Purwar, and Park. Having reversed these rejections
of claim 1, we necessarily reverse this obviousness rejection further
including Nakar, which does not provide a reason to include a divalent
cation in the fluoroquinolone composition when the prior art teaches that
such a divalent cation will reduce antibiotic activity and uptake (FF 9-10).
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SUMMARY
In summary, we reverse the rejection of claims 1-5, 7, 8, 11-18, 20-28,
30, 31, 33, 46, and 47 under 35 U.S.C. § 103(a) as obvious over Al-Razzak
and Purwar.
We reverse the rejection of claims 1-5, 7, 8, 11-18, 20-28, 30, 31, 33,
46, and 47 under 35 U.S.C. § 103(a) as obvious over Purwar and Park.
We reverse the rejection of claims 29, 32, and 34 under 35 U.S.C.
§ 103(a) as obvious over Al-Razzak, Purwar, Park, and Nakar.

REVERSED

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