Ex parte Chang et al.

Board of Patent Appeals and Interferences

Mar 29, 1999

07864210 (B.P.A.I. Mar. 29, 1999)

Application for patent filed April 3, 1992. According1
to applicants, the application is a continuation of
Application 07/451,073, filed December 15, 1989; which is a
continuation of Application 06/880,957, filed June 26, 1986,
Abandoned; which is a continuation of Application 06/521,575,
filed August 9, 1983.
1
THIS OPINION WAS NOT WRITTEN FOR PUBLICATION
The opinion in support of the decision being entered today
(1) was not written for publication in a law journal and
(2) is not binding precedent of the Board.
Paper No. 35
UNITED STATES PATENT AND TRADEMARK OFFICE
_____________
BEFORE THE BOARD OF PATENT APPEALS
AND INTERFERENCES
_____________
Ex parte ALLISON S. CHANG, JAMES E. BOYD,
RICHARD M. JOHNSON and HAROLD O. KOCH
_____________
Appeal No. 95-4491
Application 07/864,2101
______________
HEARD: March 8, 1999
_______________
Before JOHN D. SMITH, HANLON, and LIEBERMAN, Administrative
Patent Judges.
HANLON, Administrative Patent Judge.
DECISION ON APPEAL
This is an appeal under 35 U.S.C. § 134 from the final
Appeal No. 95-4491
Application No. 07/864,210
We note that appellants have incorrectly copied claim 262
in the appendix to the appeal brief. A corrected copy of
claim 26 has been reproduced in this Decision on Appeal.
2
rejection of claims 1, 9, 13, 19, 21, 23-28 and 30-32, all of
the claims pending in the application. Claims 1 and 26 are2
illustrative of the subject matter on appeal and read as
follows:
1. A method for the protection of human or animal
ophthalmic endothelial or epithelial cells subject to trauma
during surgery which comprises administering a therapeutically
effective amount of a stable, viscous, aqueous composition to
said cells during surgery, said aqueous composition consisting
essentially of a mixture of chondroitin sulfate and sodium
hyaluronate in an aqueous buffer, each of said chondroitin
sulfate and said sodium hyaluronate being contained in said
aqueous buffer in a concentration of about 0.1 to 50 wt. %,
said mixture exhibiting a synergistic viscosity which exceeds
the sum of the individual viscosities of said chondroitin
sulfate and sodium hyaluronate.
26. A stable, viscous, buffered aqueous solution which
comprises a mixture of chondroitin sulfate at a concentration
of about 0.1 to 50 wt. % and sodium hyaluronate at a
concentration of about 0.1 to 50 wt. %, said mixture
exhibiting a synergistic viscosity effect which is sufficient
to exceed the sum of the individual viscosities of said
chondroitin sulfate and said sodium hyaluronate.
The references relied upon by the examiner are:
Kawano et al. (Kawano) 3,405,120 Oct. 8, 1968
Balazs 4,141,973 Feb. 27, 1979
Pape 4,328,803 May 11, 1982
Japan Pharmaceutical Information Center (Editors), DRUGS IN
Appeal No. 95-4491
Application No. 07/864,210
3
JAPAN ETHICAL DRUG EDITION 1975, p. 216 (Tokyo, Japan, Yakugyo
Jiho Co., Ltd., Aug. 10, 1975) (referred to hereinafter as
"Drugs in Japan").
Appeal No. 95-4491
Application No. 07/864,210
Claims 24 and 28 were also finally rejected under 3
35 U.S.C. § 112, first paragraph, for lack of adequate
descriptive support. However, this rejection was withdrawn by
the examiner. See Answer, p. 2.
4
Chakrabarti et al. (Chakrabarti), "Conformational Studies of
Vitreous Polysaccharides," in The Association for Research in
Vision and Ophthalmology, Incorporated MEETING SCHEDULE, p. 97
(Sarasota, FL, Spring Meeting, April 25-29, 1974).

The sole issue in this appeal is whether claims 1, 9, 13,
19, 21, 23-28 and 30-32 were properly rejected under 35 U.S.C.
§ 103 as being unpatentable over the combination of Pape,
Balazs, Healon, Kawano, Drugs in Japan, and Chakrabarti.3
Discussion
The claims on appeal are directed to a composition
comprising a mixture of chondroitin sulfate and sodium
hyaluronate in an aqueous buffer (see claim 26) and a method
of using the composition for protecting human or animal
ophthalmic endothelial or epithelial cells subject to trauma
during surgery (see claim 1). The mixture is said to exhibit
an unexpectedly synergistic viscosity which exceeds the sum of
the individual viscosities of the chondroitin sulfate and
sodium hyaluronate.
According to appellants (Specification, pp. 2-3):
Appeal No. 95-4491
Application No. 07/864,210
5
Since human corneal endothelial cells are not
known to reproduce, it is of vital importance to
Appeal No. 95-4491
Application No. 07/864,210
6
protect endothelia to prevent cell damage prior to
subjection to anticipated trauma, such as surgery
. . . .
Macromolecules heretofore employed in the
protection of corneas include chondroitin sulfate
and sodium hyaluronate. The use of a chondroitin
sulfate solution for the protection of corneal
surface tissue is described in a “CHONDRON” product
monogram, Kakan Pharmaceutical Company, Ltd., Tokyo,
Japan, 1981. The use of sodium hyaluronate as an
aid in ophthalmic surgery is described in a “HEALON”
product monogram, Pharmacia Laboratories,
Piscataway, New Jersey, 1980.
According to appellants, solutions containing chondroitin
sulfate or sodium hyaluronate alone have not met with complete
satisfaction (Specification, p. 3). However, appellants’
claimed composition, comprising a mixture of chondroitin
sulfate and sodium hyaluronate in an aqueous buffer, is said
to effectively protect human and animal endothelial and
epithelial cells exposed to trauma (Specification, p. 2).
More particularly, appellants are said to have discovered that
a mixture of chondroitin sulfate and sodium hyaluronate in an
aqueous buffer solution exhibits surprisingly high viscosity
offering superior protection to corneal surface cells during
surgery and aiding in healing after trauma (Specification, p.
3).
Appeal No. 95-4491
Application No. 07/864,210
Pape and Balazs, disclosing the use of a sodium salt4
of hyaluronic acid to protect eye tissue during surgery, are
merely cumulative of the teachings in Healon.
7
According to appellants, viscosity is affected by factors
such as molecular weight (Specification, p. 5), buffer
solution (Specification, p. 9), temperature (Specification, p.
10), and shear rate (Specification, p. 10). Nevertheless, the
mixture of chondroitin sulfate and sodium hyaluronate in an
aqueous buffer solution is said to exhibit an unexpectedly
synergistic viscosity which exceeds the sum of the individual
viscosities of the chondroitin sulfate and sodium hyaluronate.

Rejection under 35 U.S.C. § 103
Claims 1, 9, 13, 19, 21, 23-28 and 30-32 are rejected
under 35 U.S.C. § 103 as being unpatentable over the
combination of Pape, Balazs, Healon, Kawano, Drugs in Japan
and Chakrabarti.
As pointed out above, Healon discloses the use of sodium
hyaluronate in ophthalmic surgery. According to Healon,4
sodium hyaluronate protects corneal endothelium and epithelium
both during and after ophthalmic surgery (p. 4). Drugs in
Appeal No. 95-4491
Application No. 07/864,210
According to appellants, that portion of Drugs in5
Japan (p. 216) relied upon by the examiner is a CHONDRON
product description. See Application 06/521,575, Paper No.
19; see also Specification, p. 3.
Kawano, disclosing the use of chondroitin sulfate to6
treat eye diseases, is merely cumulative of the teachings in
Drugs in Japan.
8
Japan discloses the use of sodium chondroitin sulfate to5
protect the cornea from contact eyeglass injury. The last6
reference relied upon by the examiner, Chakrabarti, discloses
a polysaccharide, ichthyosan, believed to be constituted of
hyaluronic acid and chondroitin-like polymer chains.
We agree with appellants that ichthyosan as disclosed in
Chakrabarti is a single molecule and not a mixture of sodium
hyaluronate and chondroitin sulfate as in the claimed
invention (Brief, p. 18; Moll Declaration of April 29, 1993,
paragraphs 4-7). Nevertheless, the teachings of Healon and
Drugs in Japan alone support a prima facie case of obviousness
under 35 U.S.C. § 103.
According to the examiner (Answer, pp. 3-4):
[I]t is clear from the art of record that both
hyaluronic acid and chondroitin sulfate were well
known in the art at the time of the instant
invention for the protection of eyes. Therefore, a
person having ordinary skill in the art at the time
Appeal No. 95-4491
Application No. 07/864,210
9
of the instant invention would have been motivate
[sic, motivated] to combine hyaluronic acid and
chondroitin sulfate and to use the resulting
composition for the protection of eyes. The above
rejection is based on the well established
proposition of patent law that no patentable
invention resides in combining old ingredients of
known properties where the results obtained thereby
are no more than the additive affects [sic, effects]
of the ingredients.
We disagree with appellants that the references, namely
Healon and Drugs in Japan, disclose different utilities, and
therefore, were not properly combined. In contrast to
In re Geiger, 815 F.2d 686, 2 USPQ2d 1276 (Fed. Cir. 1987),
the teachings in Healon and Drugs in Japan provide a
suggestion supporting their combination. Both references
disclose that their compositions protect corneal tissue from
injury. See In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ
1069, 1072 (CCPA 1980) (“[i]t is prima facie obvious to
combine two compositions each of which is taught by the prior
art to be useful for the same purpose, in order to form a
third composition which is to be used for the very same
purpose"). Furthermore, there is no reason to believe that
resulting injury to corneal tissue during surgery differs from
injury to corneal tissue caused by other trauma. See
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Application No. 07/864,210
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Specification, p. 2 (“This invention relates to compositions
for protecting both human and animal endothelial and
epithelial cells which are subject to exposure to trauma”).
Therefore, one having ordinary skill in the art would have
expected a mixture of sodium hyaluronate and chondroitin
sulfate to protect corneal tissue from injury caused by
surgery or other trauma. See In re O’Farrell, 853 F.2d 894,
904, 7 USPQ2d 1673, 1681 (Fed. Cir. 1988) (“[f]or obviousness
under § 103, all that is required is a reasonable expectation
of success”).
Nevertheless, appellants rely on three declarations
(Chang Declarations of July 27, 1984, and August 5, 1985, and
Hasskarl Declaration of July 29, 1988) to rebut the prima
facie case of obviousness. The Chang Declaration of July 27,
1984, is said to demonstrate that the mixture encompassed by
the claims on appeal exhibits an unusually high stability at
room temperature (Brief, p. 19).
Viscosity and osmolality for a composition of chondroitin
sulfate/sodium hyaluronate were said to have been measured
after storage at 4EC and 23EC for up to 183 days. The data at
room temperature is said to have been plotted in Figures 1 and
Appeal No. 95-4491
Application No. 07/864,210
11
2 attached to the declaration. In comparison, Figure 3 is
said to illustrate the osmolality of a chondroitin sulfate
solution at room temperature, and Figure 4 is said to
illustrate the viscosity of a sodium hyaluronate solution at
room temperature.
The declaration and evidence presented in support thereof
are inconclusive for several reasons. First, the osmolality
of the chondroitin sulfate solution at 4EC and the sodium
hyaluronate solution at 4EC and 23EC have not been included.
Second, the viscosities of the sodium hyaluronate solution
appear to have been plotted on logarithmic graph paper. In
contrast, the viscosities of the chondroitin sulfate/sodium
Appeal No. 95-4491
Application No. 07/864,210
12
hyaluronate solution appear to have been plotted on linear
graph paper. Finally, the viscosities of chondroitin sulfate
at 4EC and 23EC have not been included.
However, the Chang Declaration of August 5, 1985, said to
demonstrate the surprisingly and unexpectedly high viscosity
of the claimed composition, is sufficient to rebut the prima
facie case of obviousness. According to Chang (Declaration of
August 5, 1985, paragraph 2):
[A] solution of methyl cellulose was mixed with a
solution of chondroitin sulfate. The viscosity of
the methyl cellulose solution was 5,857 CPS, and the
viscosity of the chondroitin sulfate solution was 3
CPS. When a solution containing both methyl
cellulose and chondroitin sulfate was prepared, the
viscosity of the mixture was found to be 5,991 CPS.
The mixture thus exhibited a viscosity of about 2%
greater than the sum of the individual viscosities
of methyl cellulose and chondroitin sulfate.
See also Specification, p. 6, line 25-p. 7, line 29. In
contrast (Chang Declaration of August 5, 1985, paragraph 3):
[A] sodium hyaluronate solution was prepared having
a viscosity of 58,700 CPS, and a chondroitin sulfate
solution having a viscosity of 10 CPS. Surprisingly
and unexpectedly solution containing both sodium
hyaluronate and chondroitin sulfate was found to
have a viscosity of 71,500 CPS. That is, viscosity
of the composition of the invention was about 22%
greater than the sum of the viscosities of the
components.
Appeal No. 95-4491
Application No. 07/864,210
13
See also Chang Declaration of August 5, 1985, paragraph 5.
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Application No. 07/864,210
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Appellants argue that the examiner’s failure to consider
the Hasskarl Declaration, said to demonstrate commercial
success of the claimed invention, is reversible error (Brief,
p. 23). For the reasons set forth above, the Chang
Declaration of August 5, 1985, rebuts the prima facie
case of obviousness. Therefore, any error by the examiner in
failing to consider the Hasskarl Declaration is harmless.
The decision of the examiner is reversed.
REVERSED
JOHN D. SMITH )
Administrative Patent Judge )
)
)
) BOARD OF PATENT
ADRIENE LEPIANE HANLON ) APPEALS AND
Administrative Patent Judge ) INTERFERENCES
)
)
)
PAUL LIEBERMAN )
Administrative Patent Judge )
ALH:svt
Appeal No. 95-4491
Application No. 07/864,210
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