Ex parte Bush et al.

Board of Patent Appeals and Interferences

Sep 27, 2001

08233663 (B.P.A.I. Sep. 27, 2001)

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publication and is not binding precedent of the Board.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. 29
UNITED STATES PATENT AND TRADEMARK OFFICE
____________
BEFORE THE BOARD OF PATENT APPEALS
AND INTERFERENCES
____________
Ex parte LAWRENCE BUSH and CHANDRA WEBB
____________
Appeal No.1997-3511
Application No. 08/233,663
____________
ON BRIEF
____________
Before ROBINSON, SPIEGEL, and ADAMS, Administrative Patent Judges.
ROBINSON, Administrative Patent Judge.
REMAND TO THE EXAMINER
Our review of the record in this appeal indicates that the case is not in a condition
which will permit meaningful review of the issues raised. Therefore, we vacate the
examiner’s rejection under 35 U.S.C. § 103 and remand the application for further
consideration of the points discussed below.

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Application No. 08/233,663
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Claims 1, 9, 14, 19, and 29 are illustrative of the claims on appeal and are
reproduced below:
1. A composition comprising factor IX, glycine, a cryoprotectant, and a
surfactant.
9. The composition of claim 1, further comprising calcium chloride.
14. The composition of claim 1, further comprising a buffering agent.
19. A composition comprising factor IX, glycine, a surfactant, and a member
selected from the group consisting of a buffering agent and a cryoprotectant.
29. The composition of claim 19, wherein said surfactant is polysorbate, wherein
said cryoprotectant is sucrose and further comprising calcium chloride.
The references relied on by the examiner are listed below:
Zolton et al. (Zolton) 4,597,966 Jul. 1, 1986
Bhattacharva et al. (Bhattacharva)5,288,853 Feb. 22, 1994
Mathews et al. (Mathews) 4,952,675 Aug. 28, 1990
Schwinn DE 4,001,451 Aug. 1, 1991
(Abstract No. 91-237793/32)
Wang et al. (Wang), "Parenteral Formulations of Proteins and Peptides: Stability
and Stabilizers," J. Parenteral Sci. and Tech., Vol. 42(S), pp S3-S26 (1988)
Appeal No. 1997-3511
Application No. 08/233,663
On the record before us, the status of claim 43 is unclear. We note the statements appearing at1
page 2 of the Appeal Brief and page 2 of the Examiner's Answer concerning the allowability of claim 43.
However,since the examiner has included claim 43 in the list of claims rejected, we have included claim 43
in our consideration of this appeal.
The Reply Brief, filed December 6, 1996 (Paper No. 24) was denied entry by the examiner in a2
letter of January 21, 1997 (Paper No. 25) and this decision by the examiner was upheld on petition under 37
CFR § 1.181. (Paper No. 28 of May 14, 1997). Therefore, we have not considered this Reply Brief in
3
Ground of Rejection
Claims 1 - 9, 11 - 14, and 16 - 43 stand rejected under 35 U.S.C. § 103. As1
evidence of obviousness, the examiner relies on an abstract of the German patent
4,001,451 to Schwinn, Wang, Zolton, Mathews, and Bhattacharva.
Background
The applicants describe the invention at pages 1 and 2 of the specification as
being directed to concentrated preparations of factor IX, useful as a bulk drug product,
wherein the compositions are either frozen, liquid, or lyophilized and comprise factor IX, a
bulking agent, such as glycine, and a cryoprotectant. Applicants state that the
cryoprotectant may be a polyol such as mannitol or sucrose. Applicants also state that the
composition may contain a surfactant and/or a buffering agent.
Discussion
In considering the issues raised by this appeal, we have carefully considered the
Examiner’s Answer of September 13, 1996 (Paper No. 23) and appellants’ Appeal Brief
filed April 15, 1996 (Paper No. 20) . Our consideration of these documents, as well as the2
Appeal No. 1997-3511
Application No. 08/233,663
reviewing this appeal.
Appellants have apparently, incorrectly identified this document, since the document supplied3
with the Brief is WO 91/10439 which reasonably appears to claim benefit of the earlier filing date of
PCT/EP90/02238.
4
underlying evidence provided by both the examiner and appellants, convince us that the
present record does not provide an adequate briefing of the issues raised by this appeal
to permit a meaningful review for the reasons which follow.
In rejecting the claims pending in this application the examiner’s principal reference
is an abstract, apparently printed from a commercial data base, of a German patent. It is
not readily apparent to us why no effort was made to obtain the underlying document and
obtain a translation thereof. Appellants, for their part, have supplied a copy of the PCT
document which is referenced as PCT/EP90/02238 (hereinafter WO 91/10439) to3
Schwinn (German language) and U.S. Patent 5,328,694 to Schwinn which appellants urge
is the English equivalent, apparently to the abstracted German Patent 4,001,451. (Brief
page 4). We would note that U.S. Patent 5,328,694 claims benefit under 35 U.S.C. § 119
to German Patent 4,001,451 and would be considered likely to correspond to some
degree with that document. However, even a cursory reading of these two documents
indicates that they differ in scope of disclosure in that the U. S. Patent does not describe
any compositions relating to Factor IX while the German patent does describe
compositions containing Factor IX.
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Application No. 08/233,663
Provided to the USPTO by The Ralph McElroy Translation Co. in August of 2001. 4
Provided to the USPTO by Schreiber Translations, Inc. in June 2001.5
5
We would, additionally, note that the appellants have described the issues raised by
this appeal as being whether the claimed compositions are non-obvious over the seven
references identified at page 3 of the Brief. The examiner notes at page 2 of the
Examiner’s Answer that only the five listed references are relied on. Since we find no
further discussion of the remaining two references, we assume this is the correct statement
of the rejection before us. However, it serves as further evidence of the confusion which
exists on this record.
Since the filing of the Examiner’s Answer, translations of both German 4,001,4514
and WO 91/10439 have become available. (Copies Attached). The issues raised by5
rejections of obviousness are a fact-intensive inquiry, both as to what is claimed and what
the state of the art is relative to the claimed invention. It stands to reason that full text
documents, whether they be English language translations of foreign language documents
or the full text English documents, will provide more facts. It is not apparent why the
examiner and appellants have satisfied themselves with attempting to determine
patentability under 35 U.S.C. § 103 on less than a complete factual record.
As stated in Gechter v. Davidson, 116 F.3d 1454, 1457, 43 USPQ2d 1030, 1033
(Fed. Cir. 1997):
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For an appellate court to fulfill its role of judicial review it must have a clear
understanding of the grounds for the decision being reviewed, (citation
omitted) . . . [which requires that] [n]ecessary findings must be expressed
with sufficient particularity to enable . . . [the] court, without resort to
speculation, to understand the reasoning of the Board, and to determine
whether it applied the law correctly and whether the evidence supported the
underlying and ultimate fact-findings.
Like the court in Gechter, this Board requires a clear understanding of the grounds for the
decision being reviewed. In this case, we find it impossible to ascertain whether the
evidence, upon which the examiner relies, reasonably supports the underlying fact findings
for the rejection under 35 U.S.C. § 103.
The Board cannot examine, in the first instance, all applications which come before
it in an ex parte appeal under 35 U.S.C. § 134. As we have stated, it has been the
experience of the Board that full text documents are always more fact filled than abstracts
of these documents. Here, for example, the abstract of German Patent 4,001,451 merely
describes a stable injectable solution of factor VIII or IX suitable for human therapy which
contains a defined amount of a natural or synthetic disaccharide which may be sucrose
and at least one amino acid which may be lysine or glycine. The abstract, also, provides
that the solution may contain CaCl . When we review the translation of the underlying2
document we find that example 3 describes a concentrated solution of Factor IX which
includes sucrose, lysine and CaCl . Whether this supports or hurts the examiner's case, it2
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remains that one obtains a clearer picture of the prior art relative to the claimed invention
when one reviews the full text document.
In addition, we would note that the translation of German Patent 4,001,451, at page
2, would appear to make a distinction between the use of cryoprecipitates of VIII and
solutions of IX. It is not clear that either the examiner or appellants have considered the
relevancy of this information. What is clear from the present record, however, is that
neither the examiner or appellants have had the opportunity to review and consider the
translations of the documents most relevant to the determination of the obviousness of the
present claimed invention. Therefore, we remand this application, with copies of these
documents and the translations, to the examiner for full consideration of whether one or
both form the proper basis for questioning the patentability of the present claims under 35
U.S.C. § 103. In so doing we offer the following remarks which we hope will be helpful and
provide guidance in considering the issues raised by this appeal.
The examiner has taken the position that the ‘451 abstract describes a composition
of the type claimed except for the presence of the buffering agent or the surfactant.
(Answer, page 4). The examiner offers Wang as teaching that “[i]t is well known in the art
that to stabilize proteins the use of stabilizers that prevent denaturation is routine.” (Id.).
The examiner urges that Wang “disclose[s] that of the factors that contribute to
denaturation, pH, detergents or physical stress are some factors that contribute to
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instability during processes such as filtration. (Id.). The examiner further urges that Wang
teaches the use of polysorbate surfactants, such as Tween , to inhibit denaturation. ®
(Answer, page 5). The examiner acknowledges that Wang does not teach the use of
histidine as the buffering agent. (Id.). However, Wang talks only in terms of proteins, in
general, and does not explicitly describe any formulations of coagulation factor proteins
which could reasonable be said to relate to factor IX of the present claims.
Further, it does not appear that the examiner fully appreciates the complete
disclosure of this reference. At page S12, column 1, 4th full paragraph, in discussing the
use of cryoprotectant with proteins the reference states "[w]ithout elaborative research, it is
difficult to delineate the true mechanism of stabilization in any particular circumstance."
Further, at pages S20-21, the reference discusses the "Special Considerations" relating
to stability of proteins under freezing conditions and lyophilization and in column 1 of page
S21 states that "proper selection of a buffer system is extremely important." At column 2,
of page S21, last full paragraph, the reference states that:
Knowledge of the mechanisms for aggregation makes it easier to
understand the stabilization observed. Molecules of surfactants composed
of a hydrophilic end group and long hydrocarbon moieties, form a
hydrophobic core of micelles in which the protein molecule can be sheltered
from interaction with another protein molecule. The presence of surfactant
also reduces the concentration of protein at the interface.
In addition, at column 1 of page S22, Wang provides a discussion of the important role that
pH plays in the stabilization of a protein or peptide. These portions of Wang would appear
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relevant to the issues raised by this appeal and particularly to arguments made by
appellants relating to the lyophilization of protein compositions.
While Wang does not specifically relate to factor IX, the remaining references,
relied on by the examiner, are more closely related to this aspect of the claimed subject
matter. For example Zolton, relied on by the examiner as disclosing the use of glycine and
histidine, describes the stabilization of plasma proteins. Since factor IX is a plasma
glycoprotein (Specification, page 1, lines 10-11), this reference would be relevant to the
claimed subject matter. Both Mathews and Bhattacharva describe compositions relating
to factor VIII and describe the incorporation of substances such as calcium chloride,
sugars, buffers, surfactants with this protein for stabilization during isolation and
purification. The examiner has urged that “stabilizers for Factor IX would also be
considered stabilizers for Factor VIII or vice versa . . . .” (Answer, page 6). However, even
where the examiner has shown that each component of the claimed composition has been
combined with a protein, even a closely related protein, there must be a suggestion or
direction to be found in the prior art which would have led one or ordinary skill in the art to
bring all components required by the claim into a single combination. It is not enough that
the individual components have been used in combination with other proteins for various
purposes. As set forth in Ecolochem Inc. V. Southern California Edison, 227 F.3d 1361,
1375, 56 USPQ2d 1065, 1075 (Fed. Cir. 2000) “[a] rejection cannot be predicated on the
mere identification . . . of the individual components of claimed limitations. Rather,
particular findings must be made as to the reason the skilled artisan, with no knowledge of
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the claimed invention, would have selected these components for combination in the
manner claimed.” There must be some reason, suggestion, or motivation found in the prior
art whereby a person of ordinary skill in the field of the invention would make the
modifications required. That knowledge can not come from the applicants' invention itself.
Diversitech Corp. v. Century Steps, Inc., 850 F.2d 675, 678-79, 7 USPQ2d 1315, 1318
(Fed. Cir. 1988); In re Geiger, 815 F.2d 686, 688, 2 USPQ2d 1276, 1278 (Fed. Cir.
1987); Interconnect Planning Corp. v. Feil, 774 F.2d 1132, 1143, 227 USPQ 543, 551
(Fed. Cir. 1985). We leave it to the examiner, in the first instance, to determine whether
the prior art would have reasonably suggested bringing the components of the presently
claimed composition together.
In this regard, we would note that appellants urge that (Brief, page 13):
immunoglobulin and factor VIII, are chemically/structurally distinguishable
from Appellants’ factor IX. Such generic disclosures are not relevant, must
less predictive, of effectively stabilizing compositions for lyophilization of
factor IX and provide no reasonable expectation of success. [Emphasis in
the original].
In rebuttal, the examiner appears to assume that, since the primary reference relates to
factor IX, it is sufficient for purposes of establishing a prima facie case that Wang and
Zolton generically relate to proteins, including plasma proteins. (Answer, page 9).
However, it is not readily apparent, from the present record, that all such proteins should be
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regarded as equivalent in this manner in the absence of a teaching to be found in the prior
art or sound scientific reasoning which would support this position.
For appellants’ part we would note initially, as the examiner did through out the
Examiner’s Answer, that the claims are not directed to a method of lyophilizing a
composition or to a lyophilized composition. Appellants acknowledge at page 10 of the
Appeal Brief that the claimed composition is “inherently” stable to both lyophilization and
prolonged storage in the freeze-dried state. Thus, any compositions containing these
ingredients which are established by the examiner as old or obvious would also be
expected to inherently be stable to lyophilization. As correctly pointed out by the examiner
the motivation to combine the ingredients of the presently claimed composition need not
be the same as that which motivated appellants to make the combination. See In re
Kemps, 97 F.3d 1427, 1430, 40 USPQ2d 1309, 1311 (Fed. Cir. 1996).
Similarly, arguments to the affect that “[r]elevant disclosures are only those relating
to factor IX formulations that protect factor IX from stresses associated with lyophilization
and that provide factor IX stability in a freeze-dried state (in the presence of little water)”
(Brief, page 11) would inappropriately limit the scope of review of the prior art on the part
of the examiner.
SUMMARY
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To summarize, the rejection of claims 1 - 9, 11 - 14, and 16 - 43 under 35 U.S.C. §
103 is vacated and the application is remanded to the examiner for consideration of the
documents supplied herewith. If upon review of these documents, the examiner remains of
the opinion that the claims on appeal are unpatentable, she should issue an appropriate
Office action which sets forth the facts and reasons in support of such a rejection and
provide appellants with the appropriate opportunity to respond thereto. We would note that
we are not authorizing a supplemental Examiner's Answer to address the issues raised by
this decision.
VACATED and REMANDED
Douglas W. Robinson )
Administrative Patent Judge )
)
)
) BOARD OF PATENT
Carol A. Spiegel )
Administrative Patent Judge ) APPEALS AND
)
) INTERFERENCES
)
Donald E. Adams )
Administrative Patent Judge )
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