Ex Parte Masters

Board of Patent Appeals and Interferences

Feb 28, 2007

10088538 (B.P.A.I. Feb. 28, 2007)

The opinion in support of the decision being entered today was not written
for publication and is not binding precedent of the Board.

UNITED STATES PATENT AND TRADEMARK OFFICE
__________

BEFORE THE BOARD OF PATENT APPEALS
AND INTERFERENCES
__________

Ex parte THOMAS N. MASTERS
__________

Appeal No. 2007-0182
Application No. 10/088,538
__________

ON BRIEF
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Before ADAMS, MILLS, and GRIMES, Administrative Patent Judges.

ADAMS, Administrative Patent Judge.

DECISION ON APPEAL
This is a decision on the appeal under 35 U.S.C. § 134 from the
Examiner’s final rejection of claims 6, 7, and 9-14, which are all the claims
pending in the application.
Claim 11 is illustrative of the subject matter on appeal and is reproduced
below:
11. A medicament for preserving and storing a heart while awaiting
transplantation consisting essentially of:
(a) a balanced isotonic solution in a physiologically acceptable
amount;
(b) cyclosporin A in an amount from about 2.5 µM to about 10 µM
per liter of solution;
and
(c) the remaining being water,
whereby said heart awaiting transplantation is preserved for up to 24
hours.

Appeal No. 2007-0182 Page 2
Application No. 10/088,538
The references relied upon by the Examiner are:
Raymond 5,693,462 Dec. 2, 1997

Massoudy et al. (Massoudy), “Cardioprotection by Cyclosporine A in
Experimental Ischemia and Reperfusion – Evidence for a Nitric Oxide-dependent
Mechanism Mediated by Endothelin,” J. Mol. Cell. Cardiol., Vol. 29, pp. 535-544
(1997)

GROUND OF REJECTION
Claims 6, 7, and 9-14 stand rejected under 35 U.S.C. § 103 as being
unpatentable over the combination of Massoudy and Raymond.
We reverse.

DISCUSSION
Appellant’s claims are drawn to a composition (claims 11-14), or method
of using a composition (claims 6, 7, 9, and 10) consisting essentially of:
(a) balanced isotonic solution in a physiologically acceptable amount (e.g.,
Krebs-Henseleit-bicarbonate buffer);

(b) cyclosporin A in an amount from about 2.5 µM to about 10 µM per liter
of solution; and

(c) water.

There is no dispute on this record that Massoudy teaches a composition
comprising cyclosporin A in Krebs-Henseleit-bicarbonate buffer with water1.
Answer, page 3. It is also undisputed on this record that the prior art fails to

1 The Examiner relies on Raymond to teach that Krebs-Henseleit buffer is a “balanced isotonic
solution in a physiologically acceptable amount.” Answer, page 3 and bridging paragraph, pages
4-5. See also Appellant’s specification (page 6), wherein Appellant confirms that Krebs-
Henseleit-bicarbonate buffer is a well known “balanced isotonic solution in a physiological
acceptable amount.”

Appeal No. 2007-0182 Page 3
Application No. 10/088,538
teach a composition with a cyclosporin concentration of about 2.5 µM to about 10
µM per liter of solution.2 Id. As Appellant points out, the concentration of
cyclosporin A required by the claimed invention “is at least three times the
amount of cyclosporin A disclosed in Massoudy . . . .” Brief, page 4.
To make up for this three-fold difference in cyclosporin concentration, the
Examiner asserts that since Massoudy teaches the “general conditions” of
Appellant’s claimed invention the claimed cyclosporin A concentration would
have been obvious to a person of ordinary skill in the art at the time the invention
was made. Answer, page 3. According to the Examiner (id.), “it is not inventive
to discover the optimum or workable ranges by routine experimentation.” In re
Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). We agree that Aller
sets out the general rule that the discovery of an optimum value of a result
effective variable in a known process is normally obvious. See also In re
Boesch, 617 F.2d 272, 276, 205 USPQ 215, 219 (CCPA 1980) (“discovery of an
optimum value of a result effective variable in a known process is ordinarily within
the skill of the art.”) We disagree, however, that Aller supports the Examiner’s
prima facie case of obviousness on this record.
Massoudy teaches that cyclosporin A is used as an immunosuppressive in
organ transplantation, and is administered “either before, with or shortly after the
beginning of cardiac reperfusion following heart transplantation, [where] its
influence on the reperfused heart may have a hemodynamic – possibly
endothelin-mediated – aspect beyond its immunosuppressive action.”

2 While Raymond discloses a solution for storing an organ awaiting transplantation, Raymond
does not teach a composition comprising cyclosporin A.

Appeal No. 2007-0182 Page 4
Application No. 10/088,538
Massoudy, page 536, column 1. To address the influence cyclosporin has on the
reperfused heart Massoudy “performed experiments on isolated guinea-pig
hearts undergoing short-term ischemia and reperfusion.” Id. According to
Massoudy, “the concentrations [(0.08µM and 0.8µM)] chosen in this study are
very close to the reference [plasma] levels [required] in patients treated with CsA
[(cyclosporin A) after heart transplantation].” Massoudy, page 537, bridging
paragraph, columns 1-2. Massoudy reports that “[t]he presence of 0.8 µM
cyclosporin[ ] A prevented loss of post-ischemic cardiac function significantly,
whereas the lower concentration of CsA (0.08 µM) was without protective effect.”
Massoudy, page 539, column 2.
Appellant explains that the reason the claimed cyclosporin concentration
differs from that used by Massoudy is because Massoudy used a cyclosporin A
concentration that is consistent with its use in patients after implantation3, rather
than a concentration that is useful for preserving a heart awaiting transplantation
as is required by Appellant’s claimed invention. We agree. As discussed above,
Massoudy’s study was directed at elaborating the “influence of cyclosporin on the
reperfused heart . . .” (Massoudy, page 536, column 1), not the effects of
cyclosporin A on a heart awaiting transplantation. Therefore, while Massoudy
teaches a composition that is similar to that set forth in Appellant’s claims, it
cannot be said that Massoudy teaches the “general conditions” of Appellant’s
claimed invention. Accordingly, we disagree with the Examiner’s assertion that it
would have been prima facie obvious to “optimize” the concentration of

3 See Massoudy, page 537, bridging paragraph, columns 1-2.

Appeal No. 2007-0182 Page 5
Application No. 10/088,538
cyclosporin A as taught by Massoudy to arrive at the composition set forth in
Appellant’s claimed invention.
For clarity, while Massoudy does speak of “isolated hearts”4, Appellant
correctly asserts that Massoudy does not address the use of a composition
comprising cyclosporin A for storage or preserving a heart awaiting
transplantation. Brief, page 4. To the contrary, Massoudy’s study is directed to
addressing the influence cyclosporine has on the reperfused heart in a model
using isolated hearts undergoing short-term ischemia and reperfusion.
Massoudy, page 536, column 1. Accordingly, while it may have been obvious to
determine the optimum values of cyclosporin A in such an experimental model,
we find no evidence that a person of ordinary skill in the art would step outside
the concentration range used by patients undergoing cyclosporin A therapy to
utilize a three-fold higher amount of cyclosporin A in Massoudy’s experimental
model. To emphasize this point we note that Massoudy is careful to use
cyclosporin A concentrations, which are “very close to the reference levels in
patients treated with . . . [cyclosporin A].” Therefore, we are not persuaded by
the Examiner’s assertion that the cyclosporin A concentrations used by
Massoudy were experimental examples, which a person of ordinary skill in the art
“would not recognize . . . as limitations on the concentrations useful in the
preparation of a composition for the preservation of a heart.” To the contrary,
Massoudy does not speak to the preservation of a heart, or the use of a

4 See e.g., Answer, page 5, wherein the Examiner finds Massoudy “teaches the use of
cyclosporin A as a cardioprotective agent in ischemia and reperfusion in isolated hearts (p. 536,
col. 2, p.[ ]539, col[. ]2).”

Appeal No. 2007-0182 Page 6
Application No. 10/088,538
cyclosporin A concentration that is outside of the concentration used to treat
patients. Raymond does not teach the use of cyclosporin A and therefore fails to
make up for the deficiencies of Massoudy.
On reflection, it is our opinion that a person of ordinary skill in the art at the
time invention was made would not have found it prima facie obvious to
“optimize” the concentration of cyclosporin A in Massoudy’s composition in the
manner necessary to arrive at the composition set forth in Appellant’s claimed
invention. Accordingly, we reverse the rejection of claims 6, 7, and 9-14 under
35 U.S.C. § 103 as being unpatentable over the combination of Massoudy and
Raymond.

REVERSED

)
Donald E. Adams )
Administrative Patent Judge )
)
) BOARD OF PATENT
)
Demetra J. Mills ) APPEALS AND
Administrative Patent Judge )
) INTERFERENCES
)
)
Eric Grimes )
Administrative Patent Judge )

DEA/jlb

Appeal No. 2007-0182 Page 7
Application No. 10/088,538
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