Ex Parte Carcasona et al

Board of Patent Appeals and Interferences

Sep 26, 2002

08333202 (B.P.A.I. Sep. 26, 2002)

1
The opinion in support of the decision being entered today was not written
for publication and is not binding precedent of the Board.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 ALFONS CARCASONA, WOLF GRIMMINGER,
PENTTI HIETALA, KLAUS WITTHOHN and HELGA ZAESKE
__________
Appeal No. 2001-1947
Application 08/333,202
__________
ON BRIEF
__________
Before WINTERS, SCHEINER, and MILLS Administrative Patent Judges.
MILLS, Administrative Patent Judge.
DECISION ON APPEAL
This is a decision on appeal under 35 U.S.C. ' 134 from the examiner's final
rejection of claims 20-22, which are the claims pending in this application.
Appeal No. 2001-1947
Application 08/333,202
2
Claims 20 and 22 are representative of the claims on appeal and read as follows.
20. Substantially pure diacetylrhein obtained by mixing a diacetylrhein containing
aloe-emodin composition with an aqueous solution at a pH of 6.5 to 7.5 and a polar
organic solvent which is incompletely miscible with said aqueous solution; subjecting the
mixture of liquid-liquid partitioning; and recovering the substantially pure diacetylrhein
from the polar organic solvent, wherein said substantially pure diacetylrhein has an
aloe-emodin component content of less than 20 ppm.
22. An antiarthritic pharmaceutical composition consisting essentially of an
artiarthritically effective dose of substantially pure diacetylrhein containing less than
20 ppm aloe-emodin components and a pharmaceutically acceptable inert carrier.
The references relied upon by the examiner are:
Friedmann 4,244,968 Jan. 13, 1981
Merck Index, 10th Ed., Abstract No. 8072, p. 1179 (1983).
Neuman, “SF-277, Antirheumatic,” Drugs of the Future, Vol. IV, No. 6, pp. 445-447
(1979)
Grounds of Rejection
Claims 20-21 stand rejected under 35 U.S.C. § 102 or in the alternative under 35
U.S.C. § 103(a) as obvious over Friedmann or Merck Index.
Claim 22 stands rejected under 35 U.S.C. § 103(a) as obvious over either
Friedmann or Merck Index.
We reverse these rejections.
DISCUSSION
Appeal No. 2001-1947
Application 08/333,202
3
In reaching our decision in this appeal, we have given careful consideration to
the appellants’ specification and claims, to the applied prior art references, and to the
respective positions articulated by the appellants and the examiner.
Rather than reiterate the conflicting viewpoints advanced by the examiner and
the appellants regarding the above-noted rejection, we make reference to the
Examiner's Answer for the examiner=s complete reasoning in support of the rejection,
and to the appellants’ Brief and Reply Brief for the appellants’ arguments thereagainst.
We have considered this appeal along with related appeal No. 2001-1259, Serial No.
08/337,671. As a consequence of our review, we make the determinations which follow.
35 U.S.C. ' 102 and 103
Claims 20-21 stand rejected under 35 U.S.C. § 102, or in the alternative under 35
U.S.C. § 103(a) as obvious over Friedmann or the Merck Index. Claim 22 stands
rejected under 35 U.S.C. § 103(a) as obvious over either Friedmann or Merck Index.
In rejecting claims under 35 U.S.C. ' 103, the examiner bears the initial burden
of presenting a prima facie case of obviousness. See In re Rijckaert, 9 F.3d 1531,
1532, 28 USPQ2d 1955, 1956 (Fed. Cir. 1993). A prima facie case of obviousness is
established when the teachings from the prior art itself would appear to have suggested
Appeal No. 2001-1947
Application 08/333,202
4
the claimed subject matter to a person of ordinary skill in the art. In re Bell, 991 F.2d
781, 783, 26 USPQ2d 1529, 1531 (Fed. Cir. 1993). An obviousness analysis requires
that the prior art both suggest the claimed subject matter and reveal a reasonable
expectation of success to one reasonably skilled in the art. In re Vaeck, 947 F.2d 488,
493, 20 USPQ2d 1438, 1442 (Fed. Cir. 1993).
It is the examiner=s position that (Answer, page 4):
The claims are product-by-process claims drawn to the compound
diacetylrhein. . . . Friedmann teaches the compound diacetylrhein and its
use for the treatment of arthritis. . . . The compound taught by Friedmann
would inherently be substantially pure, essentially free from aloe-emodin
derivatives.
According to the examiner, “[t]here is no apparent difference in the com- pounds.
. . . To the extent that the purity of the compound of the reference and that of
the claims differ, the claims are rejected under 35 U.S.C. ' 103(a)” (Answer, page 4) .
Merck also teaches the compound diacetylrhein and its use as an antirheumatic. The
examiner argues there is no apparent difference between the claimed compound and
the Merck compound. Id.
With respect to claim 22, the examiner finds that the composition of claim 22
reads on a water solution of the diacetylrhein compound, citing Friedmann, column 8,
lines 35 and 54 and Merck Index, Abstract 8072, page 1179. Answer, page 4.
Appeal No. 2001-1947
Application 08/333,202
1 See Response under 37 CFR § 1.111 dated March 17, 1997, pages 5-6 and
attachment 108 (Paper No. 15).
5
Assuming, arguendo, that the examiner has presented a prima facie case of
obviousness, appellants provide argument, and rebuttal evidence in the form of a
Declaration under 37 CFR § 1.132 of Dr. Grimminger.
Appellants first argue that “[n]owhere does Friedmann disclose the purity of his
[purified diacetylrhein].” Brief, page 4. Appellants further argue that, contrary to the
examiner's assertion, Friedmann's pharmaceutical use of diacetylrhein cannot be
equated to less than 20 ppm aloe-emodin content. Appellants argue that evidence of
record1 shows that Proter, Friedmann's assignee, produces a diacetylrhein having a
much higher aloe-emodin content. Id.
In particular, appellants have made of record Analysis Certificates “which permit
a direct comparison of the product according to the state-of-the-art with the product of
the method of the now claimed invention.” Paper No. 15, page 5. The comparison
contains the results of the analysis of three batches of diacetylrhein prepared by the firm
of Proter, (U.S. Patent No 4,244,968 (Friedmann) and DE 27 11 493). The appellants
tested the Proter product and found an aloe-emodin content of 1400 ppm, 2000 ppm
and 900 ppm, respectively. Paper No. 15, page 6. In contrast, appellants provided
multiple batch analysis of diacetylrhein prepared by the claimed process which indicated
an aloe-emodin content of 2 ppm. Id. Thus, appellants argue there is no
Appeal No. 2001-1947
Application 08/333,202
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teaching in Friedmann that less than 20 ppm aloe-emodin content of diacetylrhein is
desirable or attainable. Brief, page 5.
With respect to the Merck reference cited by the examiner, appellants argue that
“Friedmann begins preparation of his product using Sennosides A and B as set forth in
the Merck Index. Friedmann then goes on to state that the “crude” rhein is collected.
Thus, Friedmann himself certainly leads the skilled artisan to the conclusion that one
would have to purify the product prepared according to the Merck Index.” Brief,
page 7.
In the Declaration under 37 CFR § 1.132 , Dr. Grimminger states:
To appreciate the significance of the now claimed invention, one must
be familiar with the state-of-the-art preparations commercially available
and the techniques used for industrial preparations. At present, there are
two principal methods of preparing diacerein on an industrial scale. . . .
These two methods are 1) oxidation of acetyl aloin and 2) acetylation of
rhein. Declaration, page 3. Dr. Grimminger states that, “[t]ests have
shown that diacerein, which according to reference 4 in the literature, is
prepared from acetylated aloin, still has a total aloe emodin content of
approximately 3500 ppm at a concentration of 95%. Following the
increase in concentration to >98% by means of recrystallization which is
required for medicinal products, the residue of total aloe emodin still
exceeds 1000 ppm.” Declaration, pages 3-4.
As to differing properties associated with the claimed diacetylrhein, Dr.
Grimminger indicates that “[g]enotoxicity tests performed parallel to the clinical
development provide positive findings in the mouse lymphoma test and in the CHO test
with a substance containing in excess of 1000 ppm triacetyl aloe emodin. Repeated
Appeal No. 2001-1947
Application 08/333,202
2 DAR is an abbreviation for diacetylrhein.
3 The second method of synthesis of diacetylrhein indicated in Neuman is
acetylation of rhein.
4 “Experiments on the Constitution of the Aloins Part I,” by Robert Robinson and
John Lionel Simonsen (Declaration, exhibit 4).
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investigations with a purified substance (66 ppm total aloe emodin residue) and with
high-purity rhein provided negative results.” Declaration, page 2.
The examiner responds to the Grimminger Declaration evidence, arguing, “based
on the assumption that applicant is right and the compound taught by Friedmann was
made by Proter, the examiner points to the article by Neuman, in Drugs of the Future
wherein, it is stated that pharmatoxicologic tests using DAR[2] produced by Proter
showed an absence of side effects, mutagenic properties and of peri and post-natal
toxicity. (Neumann [sic], page 446).” Answer, page 5.
The examiner further argues that Dr. Grimminger states that the “second method
referred to by Neuman in Drugs of the Future[3] yields a DAR having greater than 1000
ppm aloe-emodin content...” Answer, pages 5-6. The examiner finds that “applicant
has made no reference to the other process disclosed by the article [Neuman].”
Answer, page 6. We disagree.
The first (other) process of synthesis of acetylrhein mentioned in Neuman is that
of oxidation of acetylbarbaloin. Dr. Grimminger has indicated in paragraph 6 of his
Declaration that reference 44 attached to the Declaration describes a process of
Appeal No. 2001-1947
Application 08/333,202
5 We take judicial notice of the fact that barbaloin is an alternative designation for
the aloin compound. See, Merck Index, 11th ed., Abstract 304, page 51, and Grant and
Hackh's Chemical Dictionary, page 26, indicating the aloins are named according to
their origin, (i.e. the plant they are derived from).
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oxidation of aloin resulting in a diacetylrhein which still has a total aloe emodin content
of approximately 3500 ppm at a concentration of 95%. Following the increase in
concentration to >98% by means of recrystallization which is required for medicinal
products, the residue of total aloe emodin still exceeds 1000 ppm. We find this
reference and process discussed in the Grimminger Declaration to be representative of
the method of preparing diacetylrhein by oxidation of barbaloin5 mentioned in Neuman.
The examiner argues that the opinion of Dr. Grimminger in the Declaration is
afforded less weight than objective data which can be independently evaluated.
Answer, page 7.
The Declaration of Grimminger must be properly weighed. Stratoflex, Inc. v.
Aeroquip Corp., 713 F.2d 1530, 1538, 218 USPQ 871, 879 (Fed. Cir. 1983)(“evidence
rising out of the so-called ‘secondary considerations’ must always when present be
considered en route to a determination of obviousness.”). The examiner finds the
statements presented in the Declaration of Grimminger to be merely opinion. We find,
however, that Dr. Grimminger's statements are supported by at least some factual basis
and evidence of the state of the art. Although factual evidence is preferable to opinion
testimony, such testimony is entitled to consideration and some weight so long as the
Appeal No. 2001-1947
Application 08/333,202
6 In re Hoeksema, 399 F.2d 269, 274, 158 USPQ 596, 601 (CCPA 1968)
[References relied upon to support a rejection under 35 U.S.C. § 103 must provide an
enabling disclosure, i.e., they must place the claimed invention in the possession of the
public.] See also In re Payne, 606 F.2d 303, 314, 203 USPQ 245, 255 (CCPA 1979);
In re Brown, 329 F.2d 1006, 1011, 141 USPQ 245, 249 (CCPA 1964). An invention is
not “possessed” absent some known or obvious way to make it.
9
opinion is not on the ultimate legal conclusion at issue. While an opinion as to a legal
conclusion is not entitled to any weight, the underlying basis for the opinion may be
persuasive. In re Chilowsky, 306 F.2d 908, 134 USPQ 515 (CCPA 1962).
In addition, although an affiant’s or declarant’s opinion on the ultimate legal issue
is not evidence in the case, “some weight ought to be given to a persuasively supported
statement of one skilled in the art on what was not obvious to him.” In re Lindell, 385
F.2d 453, 456, 155 USPQ 521, 524 (CCPA 1967). The weight attached to evidence of
secondary considerations depends upon its relevance to the issue of obviousness and
the amount and nature of the evidence.
We are persuaded by the argument and evidence presented by appellants.
Appellants have previously argued that both Friedmann and Merck fail to disclose an
enabling process for obtaining a substantially pure composition and thus the rejections
of the claims under 35 U.S.C. §§ 102 and 103 are improper, citing In re Hoeksema.6
Paper No. 12, page 3. We agree. In our view, appellants have provided sufficient
evidence to support the position that the prior art products and methods of making
diacetylrhein are not, and do not enable a method of making a compound having the
Appeal No. 2001-1947
Application 08/333,202
10
claimed purity. In our view, this evidence has been insufficiently rebutted by the
examiner.
In our view, and consistent with legal precedent, a compound in purer or modified
form may, if unobvious in that form, be patentable over the same compound as it
existed in the prior art but the claims thereto must be limited so as to exclude from the
scope thereof, the compound as it existed in nature. In re Kebrich, 201 F.2d 951, 954,
96 USPQ 411, 413 (CCPA 1953). Compare In re Williams, 171 F.2d 319, 320, 80
USPQ 150, 152 (CCPA 1948). We find appellants have sufficiently limited the
scope of their purer form of diacetylrhein to a diacetylrhein containing less than 20 ppm
aloe-emodin components.
It has also been held that compound/substance extracted from its parent material
even in purer form is patentable only if it possesses a utility not possessed by the
patent material and not evident from the art. Ex parte Reed, 135 USPQ 34
(Bd. App. 1962). In our view, appellants have established that the state of the art is
that prior art methods of preparing diacetylrhein, and therefore prior art products
produced from these methods, have not provided a diacetylrhein product with less than
20 ppm of aloe-emodin. Appellants also provide evidence that the claimed product
differs from prior art products in its mutagenicity properties.
Appeal No. 2001-1947
Application 08/333,202
11
After evidence or argument is submitted by the applicant in response to an
obviousness rejection, "patentability is determined on the totality of the record, by a
preponderance of evidence with due consideration to persuasiveness of argument." In
re Oetiker, 977 F.2d 1443, 1445, 24 USPQ2d 1443, 1444 (Fed. Cir. 1992); see In re
Piasecki, 745 F.2d 1468, 1471-72, 223 USPQ 785, 787 (Fed. Cir. 1984) ("All evidence
on the question of obviousness must be considered, both that supporting and that
rebutting the prima facie case."). On balance, we believe that the totality of the
evidence presented by the examiner and appellants weighs in favor of finding the
claimed invention nonobvious in view of the cited references. The rejection of the
claims for anticipation, or in the alternative for obviousness of the claimed invention, is
reversed.
Other Issue
Upon return of the application to the examiner, it is recommended that the
examiner review Serial No. 08/337,671 (Appeal No. 2001-1259) to determine if any
double patenting issues exist, in particular between claim 22 of the pending application
and claim 20 of Serial No. 08/337,671.
Appeal No. 2001-1947
Application 08/333,202
12
CONCLUSION
The rejection of claims 20-21 under 35 U.S.C. § 102, or in the alternative under
35 U.S.C. § 103(a) as obvious over Friedmann or Merck Index is reversed. The
rejection of claim 22 under 35 U.S.C. § 103(a) as obvious over Friedmann or Merck
Index is reversed. The examiner should review the application for double patenting
issues, as discussed herein.
REVERSED
SHERMAN D. WINTERS )
Administrative Patent Judge )
)
)
) BOARD OF PATENT
TONI R. SCHEINER )
Administrative Patent Judge ) APPEALS AND
)
) INTERFERENCES
)
DEMETRA J. MILLS )
Administrative Patent Judge )
Appeal No. 2001-1947
Application 08/333,202
13
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