Ex parte CACECI et al.

Board of Patent Appeals and Interferences

Apr 14, 1998

07814220 (B.P.A.I. Apr. 14, 1998)

Application for patent filed December 23, 1991. Accord-1
ing to applicants, the application is a continuation of Appli-
cation 07/588,437, filed September 25, 1990, now abandoned.
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not binding precedent of the Board.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. 23
UNITED STATES PATENT AND TRADEMARK OFFICE
_____________
BEFORE THE BOARD OF PATENT APPEALS
AND INTERFERENCES
_____________
Ex parte THOMAS CACECI,
THOMAS E. TOTH
and MARIA B.W. SZUMANSKI
_____________
Appeal No. 95-2041
Application 07/814,2201
______________
ON BRIEF
_______________
Before WILLIAM F. SMITH, GRON and WEIMAR, Administrative
Patent Judges.
WEIMAR, Administrative Patent Judge.
DECISION ON APPEAL
Appeal No. 95-2041
Application 07/814,220
2
This is an appeal from the examiner's decision finally
rejecting claims 6, 11, 17-21, and 32-47. Appealed claims 48
and 49 were canceled by appellants in Paper No. 20, an amend-
ment filed subsequent to the Examiner's Answer on February 2,
1994. Note that on this amendment "Please enter" is marked in
the left margin, however, claims 48 and 49, which appear in
Paper No. 14, an amendment filed April 1, 1993, have not been
properly marked as canceled.
Claims 6, 17, 21, and 43 are illustrative of the subject
matter of the claims on appeal and read as follows:
6. A synthetic DNA sequence having a sequence of nucleo-
tides coding for an antifreeze polypeptide modeled after the
antifreeze polypeptide found in winter flounder having greater
than five repeats of an eleven amino acid sequence where the
first and fourth amino acids in said eleven amino acid se-
quence are selected from the group consisting of threonine,
asparagine, glutamine, glutamic acid, serine and aspartic acid
and the second, third and fifth through eleventh amino acids
in said eleven amino acid sequence are selected from the group
consisting of alanine, glycine, lysine, isoleucine, valine,
serine and leucine.
17. A gene having a deoxyribonucleic acid sequence as
shown in Figure 4.
21. A bacterial host having the characteristics of ATCC
deposit No. 68425.
43. A synthetic DNA sequence having a sequence of nu-
cleotides coding for an antifreeze polypeptide modeled after
the antifreeze polypeptide found in winter flounder comprising
Appeal No. 95-2041
Application 07/814,220
3
a sequence of nucleotides coding for a protein which has an
amino acid sequence defined by blocks 1-6 of Figure 4.
The references relied upon by the examiner are:
Houghten 4,886,663 Dec. 12, 1989
Gourlie et al. (Gourlie), "Winter Flounder Antifreeze Pro-
teins: A Multigene Family," J. Biol. Chem., Vol. 259, No. 23,
pages 14960-14965 (1984).
Peters et al. (Peters), "Biosynthesis of Winter Flounder
Antifreeze Proprotein in E. coli," Protein Eng., Vol. 3, pages
145-151 (1989).
Scott et al. (Scott), "Structural Variations in the Alanine-
Rich Antifreeze Proteins of the Pleuronectinae," Eur. J.
Biochem., Vol. 168, pages 629-633 (1987).
Chakrabartty et al., (Chakrabartty), "Structure-Function
Relationship In A Winter Flounder Antifreeze Polypeptide,"
J. Biol. Chem., Vol. 265, pages 11313-11316 (1989).
Williams et al. (Williams), WO 88/05082, July 14, 1988.
Ferrari et al. (Ferrari), WO 88/03533, May 19, 1988.
Shen, "Multiple Joined Genes Prevent Product Degradation in
Escherichia coli," Proc. Natl. Acad. Sci., Vol. 81, pages
4627-4631 (August 1984).
Doel et al. (Doel), "The Expression in E. coli of Synthetic
Repeating Polymeric Genes Coding For Poly(L-Aspartyl-L-Phenyl-
alanine)," Nucl. Acids Res., Vol. 8, No. 20, pages 4575-4592
(September 1980).
Kempe et al. (Kempe), "Multiple-Copy Genes: Production and
Modification of Monomeric Peptides From Large Multimeric
Fusion Proteins", Gene, Vol. 39, pages 239-245 (1985).
Appeal No. 95-2041
Application 07/814,220
4
Willson et al., "A Simple Method For Constructing Directly
Repeated Multimeric DNA Segments," Gene Anal. Techn., Vol. 2,
pages 77-82 (1985).
The rejection of claims 17, 18, 48 and 49 under 35 U.S.C.
§ 112, second paragraph, presented in the Examiner's Answer,
mailed December 6, 1993, has been obviated, as indicated in
the Supplemental Examiner's Answer, mailed February 9, 1994.
Claims 6, 11 and 32-39 stand rejected under 35 U.S.C. §
112, first paragraph, as being based on a disclosure which
fails to provide a written description which would have en-
abled any person skilled in the art to which it pertains to
practice the claimed invention throughout the full scope of
the claims without undue experimentation.
Claims 6, 11, 17-21 and 32-47 stand rejected under 35
U.S.C. § 103 over a combination of all of the above listed
references.
We vacate the examiner's rejections with respect to
claims 6, 11, 21 and 32-47, make new grounds of rejection with
respect to these claims under the provisions of 37 CFR §
1.196(b); and reverse the examiner's rejection with respect to
claims 17-20.
Appeal No. 95-2041
Application 07/814,220
5
BACKGROUND
Antifreeze polypeptides are known in the art. These
polypeptides have been found in fish which live in arctic
waters. The polypeptides prevent the formation of ice in the
body fluids of these fish. See the specification at page 3,
lines 8-22. The specification describes a specific protein,
shown in Figure 4 of the application, which is a variant of an
antifreeze polypeptide found in winter flounder. Figure 4
also indicates a specific DNA sequence encoding this variant
antifreeze polypeptide. The prior art describes an antifreeze
polypeptide found in winter flounder and its production by
bacteria that have been transformed with DNA which encodes the
polypeptide. See pages 3 through 6 of the specification.
Discussion
Having considered the entire record in this appeal, we
have determined that some of the claims presented are indefi-
nite under 35 U.S.C. § 112, second paragraph. Accordingly, we
institute a new ground of rejection of claims 6, 11, 21 and
32-47 under this statute infra. Since the metes and bounds of
claims 6, 11, 21 and 32-47 cannot be readily ascertained,
Appeal No. 95-2041
Application 07/814,220
6
consideration of the issues raised under the enablement re-
quirement of 35 U.S.C. § 112, first paragraph, and obviousness
under 35 U.S.C. § 103 would be premature with respect to these
claims. In re Moore, 439 F.2d 1232, 1235, 169 USPQ 236, 238
(CCPA 1971)(One is not in position to determine whether a
claim is enabled under the first paragraph of 35 U.S.C. § 112
until the metes and bounds of that claim are determined under
the second paragraph of this section of the statute.). In re
Steele, 305 F.2d 859, 862, 134 USPQ 292, 295 (CCPA
1962)(Analyzing claims based on "speculation as to meaning of
the terms employed and assumptions as to the scope of such
claims" is legal error.).
With respect to claims 17-20 we will reach the merits of
the examiner's rejection under 35 U.S.C. § 103. We note these
claims had been rejected under 35 U.S.C. § 112, first
paragraph in the Final Rejection, mailed June 24, 1993, Paper
No. 17. However, the Examiner's Answer, mailed December 6,
1995, Paper No. 19, presents the claims that are rejected
under 35 U.S.C. § 112, first paragraph, as limited to "claims
6, 11, and 32-39." See page 11 of the Examiner's Answer, the
Appeal No. 95-2041
Application 07/814,220
7
second complete paragraph. Thus, claims 17-20 are not
presently rejected under 35 U.S.C. § 112, first paragraph.
New Ground of Rejection Under 37 CFR § 1.196(b)
Claims 6, 11, 21 and 32-47 are rejected under 35 U.S.C. §
112, second paragraph, as being indefinite for failing to
particularly point out and distinctly claim the subject matter
which applicants regard as their invention.
1."modeled after"
Claims 6, 11 and 32-47 recite, either expressly or via
dependence on a claim that recites, a DNA sequence "coding for
an antifreeze polypeptide modeled after the antifreeze
polypeptide found in winter flounder." The metes and bounds
of this language are not apparent, nor is there a specific
definition in the specification that would provide a
structural and/or functional limitation of the claimed DNA
compounds. Does the winter flounder possess more than one
gene which encodes a protein which has an activity such that
it can be classified as an "antifreeze polypeptide?" How
close to which protein produced by a winter flounder must a
compound be in order to be considered as "modeled after" the
Appeal No. 95-2041
Application 07/814,220
8
protein? We note that the as-filed specification states, in
pertinent part, from line 23 of page 3 to line 5 of page 4,
that:
Figure 1 shows the primary amino acid
sequence of a native AFP isolated from
the winter flounder.... This is a class
1 or alanine rich AFP. There are 38
amino acids (SEQ ID NO:1)... The AFP
of SEQ ID NO:1 is but one example of
a wide variety of AFPs.
It is not clear what degree of ice suppression activity, if
any, a protein encoded by the claimed DNA compounds must have
before falling within the scope of the indicated claims.
Claims 6, 11, 32, 33, and 36-42 each recite, or is
dependent on a claim which recites, the presence of codons in
the DNA compound which encode multiples of an eleven amino
acid sequence and limit the choices of those eleven amino
acids by the following language:
where the first and fourth amino acids in
said eleven amino acid sequence are selected
from the group consisting of threonine,
asparagine, glutamine, glutamic acid, serine
and aspartic acid and the second, third and
fifth through eleventh amino acids in said
eleven amino acid sequence are selected
from the group consisting of alanine, glycine,
lysine, isoleucine, valine, serine and leucine.
Appeal No. 95-2041
Application 07/814,220
9
Within the genus of possible eleven amino acid sequences
claimed thus, is the species consisting of eleven serines. In
addition, the language in the claims includes multiple eleven
amino acid sequences which are devoid of alanine. The protein
from winter flounder described in Figure 1 contains only one
serine and contains 26 alanines of the 38 amino acids. This
disparity exemplifies the breadth of the indicated proteins
that are to be encoded by the claimed genus of DNA compounds
and the protein that they are to be "modeled after".
We note that the words "modeled after the antifreeze
polypeptide found in winter flounder" were added to the claims
for the first time via an amendment filed December 23, 1991,
Paper No. 10. On page 10 of this submission, at line 4
applicants state, "This addition was suggested by the
Examiner...." Applicants then refer to a declaration of one
of the inventors (Caceci), previously submitted in the course
of prosecution, and a publication by Kao et al., for a
discussion of the differences between winter flounder, ocean
pout and sea raven AFPs. However, such does not remove the
statutory requirement that the claims particularly point out
and distinctly claim the subject matter which applicants
Appeal No. 95-2041
Application 07/814,220
We note that the number 68425 has not actually been2
inserted into page 26, line 4, of the specification, however
the direction to do so is contained in a partially entered
amendment, "Amendment A", filed January 15, 1991, Paper #2, in
parent Application No. 07/588,437.
10
regard as their invention, nor substitute for the requirement
under 35 U.S.C. § 112, first paragraph, that the invention be
described in the as-filed specification.
2. "host having the characteristics of"
Claim 21 is indefinite in that it recites:
A bacterial host having the characteristics
of ATCC deposit No. 68425.
In pertinent part, the specification at page 26, lines 1-4
recites:
Therefore, a deposit has been made with the
American Type Culture Collection (ATCC) of
Rockville, Maryland, of the plasmid PgX28L
in the E. coli strain DH5" and has ATCC
number 68425.2
The scope of the claimed products is not clear. Which
characteristics of the deposited culture are limitations on
the claimed products? Does the claim include a bacterial host
which has been transformed with plasmid PgX28L but which is
incapable of expressing any of the DNA contained in the
Appeal No. 95-2041
Application 07/814,220
11
plasmid? Does the claim include bacterial cultures other than
E. coli? It is not ascertainable which cells, beyond the
cells in the culture held at the ATCC, are within the metes
and bounds of claim 21.
3."an amino acid sequence defined by blocks...of Figure 4"
Claims 43-47 refer to the blocks of Figure 4. Claims 43-
46 commonly recite: "A synthetic DNA sequence ... comprising a
sequence of nucleotides coding for a protein which has an
amino acid sequence defined by blocks ... of Figure 4." The
only variation in these four claims is that a specific segment
of "blocks" from Figure 4 is recited in each one of claims 43-
46. Claim 47 recites that the claimed DNA encodes "a protein
which has an amino acid sequence with greater than five of the
eight blocks shown in Figure 4." The specification refers to
the blocks of Figure 4 at page 10, lines 4-16. The blocks are
indicated in Figure 4 by two-directional arrows. Blocks 1-8
are contiguous in Figure 4. The specification also
contemplates adding segments which are 11 amino acids in
length at the PST1 site shown in block 7 of Figure 4. Such an
addition would result in a non-contiguous association of
Appeal No. 95-2041
Application 07/814,220
12
multiple segments (see the specification from page 14, line
15, through page 16, line 1). It is not clear whether the
language "defined by blocks ... of Figure 4" or "with greater
than five of the eight blocks shown in Figure 4" is inclusive
of the additional segments discussed on pages 14-16 of the
specification.
Claim Interpretation
In contrast to the above-noted ambiguity, when referring
to Figure 4, claims 17-20 recite "as shown in Figure 4." Page
8 of the specification at lines 22-25, describes Figure 4 as
"a base pair sequence ... and a synthesized amino acid
sequence for an AFP polypeptide WF8R wherein the gene wf8r
codes for the AFP WF8R" (emphasis added). Page 9 of the
specification at lines
20-25, refers to Figure 4, stating:
Referring now to the drawings, and more
particularly to Figure 4, there is shown
a synthetic AFP peptide (SEQ ID NO:2) and
a synthetic gene (comprised of DNA SEQ ID
NO:3 and DNA SEQ ID NO:4) coding for the
AFP peptide having SEQ ID NO:2.(emphasis added)
Appeal No. 95-2041
Application 07/814,220
13
Thus, we hold that claims 17-20 recite the DNA and amino acid
sequences of Figure 4 as they are shown in Figure 4, i.e.
uninterrupted by any additional DNA or amino acids. The
"having" and "has" recitations of these claims result in
opening the claims to sequences which are inclusive of the
sequences of Figure 4, but which contain additional
nucleotides or amino acids on either end of the corresponding
Figure 4 sequence.
The examiner's rejection under 35 U.S.C. § 112, first
paragraph
We vacate the examiner's rejection of claims 6, 11, and
32-39 under 35 U.S.C. § 112, first paragraph. In doing so, we
emphasize that we have not decided the merits of the issues
raised by the examiner therein. If prosecution is continued
on this subject matter and claims are presented which meet the
requirements of 35 U.S.C. § 112, second paragraph, the
examiner should revisit these issues.
The examiner's rejection under 35 U.S.C. § 103
We vacate the examiner's rejection of claims 6, 11, 21,
and 32-47 under 35 U.S.C. § 103. In doing so, we emphasize
Appeal No. 95-2041
Application 07/814,220
14
that we have not decided the merits of the issues raised by
the examiner therein. If prosecution is continued on this
subject matter, and claims are presented which meet the
requirements of 35 U.S.C. § 112, second paragraph, the
examiner should revisit these issues.
Claims 17-20 stand rejected under 35 U.S.C. § 103 over
Gourlie and Peters in view of Chakrabartty, Houghten and Scott
and further in view of any one of Williams, Ferrari, Shen,
Doel, Kempe or Willson.
We reverse this rejection. A prima facie case of
obviousness has not been presented by the Examiner.
The combined prior art teachings do not provide a
reasonable basis for increasing the number of 11 amino acid
sequence repeats in the antifreeze polypeptide of winter
flounder to establish that the claimed genes and transformed
hosts which produce such polypeptides would have been obvious
to a person having ordinary skill in the art at the time of
the invention. The reasoning presented in the rejection is
stated in the Examiner’s Answer, beginning on the last line of
page 13 and continuing through lines 1-14, of page 14, as:
Appeal No. 95-2041
Application 07/814,220
15
It would have been further obvious to enhance
the antifreeze properties of the protein by
adding additional repeat sequences as suggested
by Chakrabartty or by amino acid substitution
as suggested by Scott, since these references
as cited above indicate that the number of ice
contact points is the limiting factor in anti-
freeze activity. Thus, increasing the number
of ice contact points by the addition of AFP
repeat sequences (note the same conclusion was
admitted by appellants from a review of Chakra-
bartty (19) and Scott, see page 12, last para-
graph, ending on page 13 of the specification),
or adding ice contact points via amino acid
substitution, or using like amino acids
instead of the naturally occurring ones were
all suggested by the prior art to enhance AFP
activity and provide both the motivation and a
reasonable expectation of enhanced AFPs.
We do not agree that "adding additional repeat sequences"
is reasonably "suggested by Chakrabartty", nor that
Chakrabartty and Scott "indicate that the number of ice
contact points is the limiting factor in antifreeze activity."
The examiner argues that Chakrabartty teaches length variation
in the right hand column of page 11315. See the sentence
bridging pages 10 and 11 of the Final Rejection. We find that
Chakrabartty there refers to "analogs which vary in length" in
the context of "repeating the experiment." Chakrabartty’s
work involves analogs of 1 repeat, 2 repeats and 3 repeats.
See Table 1 of Chakrabartty on page 11314. The reference does
Appeal No. 95-2041
Application 07/814,220
16
not teach lengthening the polypeptide by adding more than
three repeats. The genes and hosts of claims 17-20, encode
and produce, respectively, polypeptides which contain the
eight specified 11-amino acid sequence "repeats" of Figure 4.
Polypeptides of this length with this number of repeats are
neither taught by nor reasonably suggested by the teachings of
Chakrabartty. Nor is a finding that the limiting factor in
antifreeze activity is the "number of ice contact points"
reasonably supported by the Chakrabartty and Scott teachings.
These references note the significance of the number of ice
contact points, but they do not lessen the significance of
other factors, including the known number of contiguous
repeats in known antifreeze polypeptides.
We disagree with the statement in the above-quoted
section of the Examiner's Answer (page 14, 7-9) which reads
"(note the same conclusion was admitted by appellants from a
review of Chakrabartty (19) and Scott, see page 12 last
paragraph, ending on page 13 of the specification)." The
cited section of the specification is not an admission of a
"conclusion...from a review of Chakrabartty and Scott."
Rather, the section of pages 12 and 13 of the specification to
Appeal No. 95-2041
Application 07/814,220
17
which the examiner refers, notes the teaching in the
Chakrabartty that "a minimum of three repeats of the basic
sequence are required for ice suppression activity." Then in
the following sentence the inventors, not Chakrabartty,
conclude "Hence, larger molecules with a greater number of
repeating sequences which can form a larger amount of hydrogen
bonds should be more effective in preventing ice crystal
growth (emphasis added)." This sentence is not an admission
that the prior art had drawn the stated generic conclusion.
Hindsight shall not form the basis of a conclusion of
obviousness under 35 U.S.C. § 103. "Both the suggestion and
the expectation of success must be founded in the prior art,
not in the applicant’s disclosure." In re Dow Chemical Co.,
837 F.2d 469, 473, 5 USPQ2d 1529, 1531 (Fed. Cir. 1988). The
prior art of record does not denominate the critical features
of appellants’ invention; i.e. genes and hosts corresponding
to the production of proteins containing the eight-repeat
sequences required by claims 17-20. As the Federal Circuit
stated in Sensonics, Inc. v. Aerosonic Corp., 81 F.3d 1566,
1570, 38 USPQ2d 1551, 1554 (Fed. Cir. 1996):
To draw on hindsight knowledge of the
Appeal No. 95-2041
Application 07/814,220
18
patented invention, when the prior art
does not contain or suggest that knowledge,
is to use the invention as a template for
its own reconstruction - an illogical and
inappropriate process by which to determine
patentability. . . . The invention must be
viewed not after the blueprint has been
drawn by the inventor, but as it would have
been perceived in the state of the art that
existed at the time the invention was made.
[citations omitted]
Thus, we hold that claims 17-20 define genes and hosts
which would not have been obvious in view of the prior art
cited by the examiner.
CONCLUSION
We reverse the rejection of claims 17-20 under 35 U.S.C.
§ 103.
We vacate the rejection of claims 6, 11, and 32-39 under
35 U.S.C. § 112, first paragraph.
We vacate the rejection of claims 6, 11, 21, and 32-47
under 35 U.S.C. § 103.
Appeal No. 95-2041
Application 07/814,220
19
We newly reject claims 6, 11, 21, and 32-47 under 35
U.S.C. § 112, second paragraph, and the provisions of 37 CFR §
1.196(b).
No time period for taking any subsequent action in
connection with this appeal may be extended under 37 CFR §
1.136(a).
REVERSED-IN-PART; VACATED-IN-PART; 37 CFR § 1.196(b)
)
WILLIAM F. SMITH )
Administrative Patent Judge )
)
)
) BOARD OF PATENT
TEDDY S. GRON )
Administrative Patent Judge ) APPEALS AND
)
) INTERFERENCES
)
ELIZABETH C. WEIMAR )
Administrative Patent Judge )
Appeal No. 95-2041
Application 07/814,220
20
Whitham & Marhoefer
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Appeal No. 95-2041
Application 07/814,220
WEIMAR
GRON
W. SMITH
REVERSED-IN-PART
VACATED-IN-PART
37 CFR 1.196(b)
Corrections: