Ex Parte Macleod

Board of Patent Appeals and Interferences

Sep 4, 2003

09238972 (B.P.A.I. Sep. 4, 2003)

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for publication and is not binding precedent of the Board.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. 14

UNITED STATES PATENT AND TRADEMARK OFFICE
__________

BEFORE THE BOARD OF PATENT APPEALS
AND INTERFERENCES
__________

Ex parte CAROL L. MacLEOD
__________

Appeal No. 2001-1651
Application No. 09/238,972
__________

ON BRIEF
__________

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 1-9, 16 and 17. As a result of a Restriction
Requirement, the only remaining claims, claim 10-15 and 18-20, have been
withdrawn from consideration, as drawn to a non-elected invention.
Claim 1, 3 and 16 are illustrative of the subject matter on appeal and are
reproduced below:
1. A method of inhibiting cationic amino acid transport comprising the
step of administering to a human or a non-human mammal an
effective dose of an antisense oligonucleotide directed against CAT2
mRNA.

3. A pharmaceutical composition comprising an antisense oligonucleotide
directed against CAT2 mRNA and a physiologically acceptable carrier.
Appeal No. 2001-1651 Page 2
Application No. 09/238,972

16. An antisense oligonucleotide directed against CAT2 mRNA.

The references relied upon by the examiner are:
MacLeod 5,312,733 May 17, 1994
Hoke et al. (Hoke) 5,585,479 Dec. 17, 1996

Gewirtz et al. (Gewirtz), “Facilitating oligonucleotide delivery: Helping antisense
deliver on its promise,” Proc. Natl. Acad. Sci. USA, Vol. 93, pp. 3161-63 (1996)

Rojanasakul, “Antisense oligonucleotide therapeutics: drug delivery and
targeting,” Advanced Drug Delivery Reviews, Vol. 18, pp. 115-31 (1996)

Branch, “A good antisense molecule is hard to find,” TIBS, Vol. 23, pp. 45-50
(1998)

GROUNDS OF REJECTION
Claims 3 and 16 stand rejected under 35 U.S.C. § 112, first paragraph, as
the specification that fails to adequately describe the claimed invention.
Claims 1-9 and 16 stand rejected under 35 U.S.C. § 112, first paragraph,
as being based on an insufficient disclosure to support or enable the scope of
the claimed invention.
Claims 3, 16 and 17 stand rejected under 35 U.S.C. § 102(b) as being
anticipated by MacLeod.
We affirm the rejection under 35 U.S.C. § 102(b) and reverse the
rejections under 35 U.S.C. § 112, first paragraph.
DISCUSSION
THE REJECTIONS UNDER 35 U.S.C. § 112, FIRST PARAGRAPH:
Written Description:
“In order to satisfy the written description requirement, the disclosure as
originally filed does not have to provide in haec verba support for the claimed
Appeal No. 2001-1651 Page 3
Application No. 09/238,972

subject matter at issue.” Purdue Pharma L.P. v. Faulding, Inc., 230 F.3d 1320,
1323, 56 USPQ2d 1481, 1483 (Fed. Cir. 2000). Nonetheless, the disclosure
must convey with reasonable clarity to those skilled in the art that the inventor
was in possession of the invention. See id. “Put another way, one skilled in the
art, reading the original disclosure, must immediately discern the limitation at
issue in the claims.” Id.
According to the examiner, (Answer, page 4), claims 3 and 16 are “drawn
to any antisense oligo which inhibits CAT2 translation and pharmaceutical
compositions comprising said antisense oligo.” Based on this interpretation of
the claims, the examiner finds (id.) that while the specification describes the
inhibitory activity of an antisense oligo consisting of SEQ ID NO: 2, the
specification fails to describe any other antisense oligo, or pharmaceutical
composition comprising such an antisense oligo, that exhibited inhibitory activity.
However, in response, appellant points out that the entire sequence of the CAT2
open reading frame was set forth in “MacLeod et al. Mol. Cell. Biol., 10:3663-
3674 (1990) and is also available from GenBank as accession no. M32485,” and
that with knowledge of the open reading frame “one skilled in the art could easily
design other effective antisense oligonucleotides.” Brief, page 12.
As set forth in Moba B.V. v. Diamond Automation Inc., 325 F.3d, 1306,
1320-21, 66 USPQ2d 1429, 1439 (Fed. Cir. 2003):
The test for compliance with § 112 has always required sufficient
information in the original disclosure to show that the inventor
possessed the invention at the time of the original filing. See …
[Vas-Cath Inc. v. Mahurkar, 935 F.2d 1555, 1561, 19 USPQ2d
1111, 1115 (Fed. Cir. 1991)] (“Adequate description of the
Appeal No. 2001-1651 Page 4
Application No. 09/238,972

invention guards against the inventor’s overreaching by insisting
that he recount his invention in such detail that his future claims
can be determined to be encompassed within his original
creation”). The possession test requires assessment from the
viewpoint of one of skill in the art. Id. at 1563-64 (“the applicant
must ... convey with reasonable clarity to those skilled in the art
that, as of the filing date sought, he or she was in possession of the
invention”) (emphasis in original); Union Oil Co. of Cal. v. Atlantic
Richfield Co., 208 F.3d 989, 997, 54 USPQ2d 1227, 1232 (Fed.
Cir. 2000) (“The written description requirement does not require
the applicant ‘to describe exactly the subject matter claimed,
[instead] the description must clearly allow persons of ordinary skill
in the art to recognize that [he or she] invented what is claimed’”)
(citation omitted). In Enzo [Biochem, Inc. v. Gen-Probe, Inc., 296
F.3d 1316, 63 USPQ2d 1609 (Fed. Cir. 2002)] and Amgen[ Inc. v.
Hoechst Marion Roussel Inc., 314 F.3d 1313, 1330, 65 USPQ2d
1385, 1397 (Fed. Cir. 2003)], the record showed that the
specification that taught one of skill in the art to make and use an
invention also convinced that artisan that the inventor possessed
the invention. Similarly in this case, the Lilly [Regents of the
University of California v. Eli Lilly & Co., 119 F.3d 1559, 43
USPQ2d 1398 (Fed. Cir. 1997)] disclosure rule does not require a
particular form of disclosure because one of skill could determine
from the specification that the inventor possessed the invention at
the time of filing.

On this record, the examiner bases his rejection on an incorrect
interpretation of the claimed invention. Contrary to the examiner’s assertion
(Answer, page 4), claims 3 and 16 do not require the inhibition of CAT2
translation. Instead, claim 16 is drawn to an antisense oligonucleotide directed
against CAT2 mRNA, and claim 3 is drawn to a composition comprising an
antisense oligonucleotide directed against CAT2 mRNA in a physiologically
acceptable carrier. We note that while a number of appellant’s claims are
directed at methods of using an antisense CAT2 oligonucleotide, none of these
claims are included in this rejection.
Appeal No. 2001-1651 Page 5
Application No. 09/238,972

In addition, the examiner failed to consider the level of skill in the art as it
relates to the claimed invention. To the contrary, by incorrectly interpreting the
claimed invention to require the claimed antisense oligonucleotide, or a
pharmaceutical composition thereof, to have the ability to inhibit CAT2 mRNA
translation the examiner created an artificial claim. The examiner then attacks
this artificial claim finding no written descriptive support in the disclosure for an
“antisense oligo that is capable of inhibiting CAT2 RNA thereby disrupting
translation of cationic amino acid transport protein … [or for] pharmaceutical
compositions comprising the antisense oligo since no evidence is provided
demonstrating the ameliorative effects of treatment with said antisense oligo.”
See Answer, page 5. These arguments, however, do not address the invention
of claims 3 and 16.
Accordingly, it is our opinion that the examiner failed to provide the
evidence necessary to establish that one of skill in the art could not determine
from the specification that the inventor possessed the invention of claims 3 and
16 at the time of filing. Accordingly, we reverse the rejection of claims 3 and 16
under 35 U.S.C. § 112, first paragraph.
Enablement:
The initial burden of providing reasons why a supporting disclosure does
not enable the claims rests with the examiner. In re Marzocchi, 439 F.2d 220,
223, 169 USPQ 367, 369 (CCPA 1971). It is the examiner’s burden to establish
that appellant’s specification does not provide a sufficient disclosure, either
through illustrative examples or terminology, for one skilled in the art to practice
Appeal No. 2001-1651 Page 6
Application No. 09/238,972

the invention as broadly as claimed without having to resort to undue
experimentation. See In re Vaeck, 947 F.2d 488, 496, 20 USPQ2d 1438, 1445
(Fed. Cir. 1991). In considering this issue, we note that appellant is not required
to disclose every parameter encompassed by the claims. See In re Angstadt,
537 F.2d 498, 503, 190 USPQ 214, 218 (CCPA 1976). Furthermore, while some
experimentation may be necessary, that does not preclude enablement; what is
required is that the amount of experimentation “must not be unduly extensive.”
Atlas Powder Co. v. E.I. DuPont de Nemours & Co., 750 F.2d 1569, 1576, 224
USOQ 409, 413 (Fed. Cir. 1984).
On this record, the examiner finds (Answer, page 5),
the specification is only enabling for claims limited to an antisense
oligo consisting of SEQ ID NO:2 and a method of inhibiting CAT2
expression using said antisense oligo. The specification does not
enable any person skilled in the art to which it pertains, or with
which it is most nearly connected, to make and/or use the invention
commensurate in scope with … [claims 1-9 and 16].

According to the examiner (Answer, page 6), “[a]lthough the specification
provides guidance on a singular antisense oligo (SEQ ID NO: 2), it is well known
by those skilled in the art that identification of target sites in a given mRNA at
which antisense oligos bind to cause inhibition of translation is an unpredictable
art.”
With reference to Hoke, the examiner finds (Answer, page 7) that
screening
different sites on a given mRNA to find oligo binding sites for
inhibition of translation, may fail to identify such sites in the 5’
untranslated region, the coding region, or in the 3’ untranslated
region of the mRNA and that an oligo binding site that is located
Appeal No. 2001-1651 Page 7
Application No. 09/238,972

only a few bases to either side of an unsuccessful target site may
give very effective inhibition of translation.

However, as appellant points out (Brief, page 15), Hoke report a 55% success
rate in obtaining effective anti-sense oligonucleotides. According to appellant
there is no reason why a similar success rate would not be expected for the
instant invention. In response, the examiner backs away from his reliance on
Hoke and agrees with appellant that Hoke reports a 55% success rate. Answer,
page 10. Nevertheless, the examiner maintains that the instant invention would
not be successful due to the unpredictability of antisense oligonucleotide therapy
and target accessibility as taught by Gewirtz and Branch. Answer, bridging
sentence, pages 10-11.
According to the examiner (Answer, page 7), Gewirtz “teach that the
inhibitory activity of an oligo depends unpredictably on both the sequence and
structure of the nucleic acid target site and the ability of the oligo to reach its
target.” Similarly, the examiner relies on Branch to teach that “‘internal
structures of target RNAs and their associations with cellular proteins create
physical barriers, which render most potential binding sites inaccessible to
antisense molecules.’” While the examiner argues that Gewirtz and Branch
address the unpredictability of antisense technology, the examiner fails to
establish a nexus between these generic references and the claims on appeal.
In addition, we find the examiner’s position to be inconsistent. According
to the examiner the specification provides an enabling disclosure of a method of
inhibiting CAT2 expression using an antisense oligo consisting of SEQ ID NO:2.
Appeal No. 2001-1651 Page 8
Application No. 09/238,972

Answer, page 5. We note that the examiner does not limit the scope of this
method to exclude antisense oligonucleotide therapy. The only reasonable
conclusion that can be drawn from the examiner’s argument is that despite the
teachings of Hoke, Gewirtz, and Branch an antisense oligo consisting of SEQ ID
NO:2 can be used in an antisense oligonucleotide therapy method for inhibiting
CAT2 expression. Thus, the generic teachings of Hoke, Gewirtz and Branch are
not applicable to appellant’s claimed methods.
According to appellant’s specification (page 27), “[t]he present invention
describes how novel antisense oligonucleotides can be employed to prevent
cationic amino acid transport, which in turn blocks production of nitric oxide in
cells such as activated macrophages or cancer cells.” Appellant’s specification
discloses (page 28), “the present invention makes available novel antisense
oligonucleotides for use in gene therapy where it may be desirable to inhibit
production of nitric oxide.” In the paragraph bridging pages 28-29, appellant’s
specification discloses that
this method will treat diseases selected from the group consisting
of sepsis, cachexia, neoplastic diseases such as Kaposi’s
sarcoma, cerebral malaria, capillary leak syndrome and
autoimmune disease. Representative autoimmune diseases
include systemic lupus erythematosus, rheumatoid arthritis and
multiple sclerosis. Representative neoplastic diseases include
breast and lung cancer.

The examiner recognizes (Answer, page 6), appellant’s “specification
teaches that CAT2 is involved in arginine transport which was shown to be
essential in nitric oxide synthesis. In addition, iNOS expression was shown to be
correlative with mammary tumorigenesis since mice with a functional iNOS gene
Appeal No. 2001-1651 Page 9
Application No. 09/238,972

developed mammary tumors more rapidly than iNOS knockout mice.” The
examiner also finds (Answer, page 5), appellant’s specification enables a method
of inhibiting CAT2 expression using an antisense oligo consisting of SEQ ID
NO:2. Therefore, it is unclear on this record, why the examiner finds (Answer,
page 6) that appellant’s “specification does not provide any guidance regarding
the administration of any type [of] antisense oligo targeted to CAT2 that would
result in an ameliorative effect of any particular pathological state nor does the
specification provide sufficient guidance that would enable a skilled artisan to
treat a pathological condition by inhibiting CAT2.” As emphasized above, it
seems clear from appellant’s specification that inhibiting CAT2 expression, using
an antisense oligo, will inhibit production of nitric oxide. Accordingly, it appears
from this record that such a method would be applicable to the diseases set forth
in appellant’s specification. The examiner offers no evidence to the contrary.
Furthermore, since appellant’s specification provides an enabling
disclosure of an antisense oligo consisting of SEQ ID NO: 2 and a method of
inhibiting CAT2 expression using this oligo, why would it require undue
experimentation to identify other antisense CAT2 oligonucleotides with a success
rate similar to that of Hoke? The examiner conceded the success rate observed
by Hoke, and that appellant’s oligonucleotide having SEQ ID NO.: 2 is effective
in a method of inhibiting CAT2 expression. In view of these findings, the
examiner failed to provide any explanation as to how the generic teachings of
Gewirtz, and Branch apply to appellant’s claimed invention. Stated differently,
Appeal No. 2001-1651 Page 10
Application No. 09/238,972

the examiner failed to provide the evidence necessary to establish that
appellant’s specification does not support appellant’s claimed invention.
To emphasize the inconsistent approach taken by the examiner, we note
that claim 17 is drawn to an antisense CAT2 oligonucleotide having the
sequence set forth in SEQ. ID. NO.: 2; and claim 2 is drawn to a method of using
an antisense CAT2 oligonucleotide having the sequence set forth in SEQ. ID.
NO.: 2. Notwithstanding the examiner’s finding that the specification enables a
method of inhibiting CAT2 expression using an antisense oligonucleotide
consisting of SEQ ID NO.: 2, the examiner excludes claim 17 from the rejection,
but includes claim 2 in the rejection.
In addition, we recognize the examiner’s reliance on Rojanasakul (Answer
page 7), which according to the examiner “gives evidence that the use of
antisense oligonucleotides in vivo caused renal failure due to toxicity of the
antisense oligonucleotide which could be due to nonspecific effects of the oligo
itself….” The examiner, however, appears to confuse the requirements under
the law for obtaining a patent with the requirements for obtaining government
approval to market a particular drug for human consumption. See Scott v.
Finney, 34 F.3d 1058, 1063, 32 USPQ2d 1115, 1120 (Fed. Cir. 1994) (“Testing
for the full safety and effectiveness of a prosthetic device is more properly left to
the Food and Drug Administration (FDA). Title 35 does not demand that such
human testing occur within the confines of Patent and Trademark Office (PTO)
proceedings”).
Appeal No. 2001-1651 Page 11
Application No. 09/238,972

Furthermore, to the extent that Rojanasakul may be relevant to the issue
of patentability, we note that Rojanasakul (page 118, carry over paragraph,
columns 1 and 2), report that thrombocytopenia and renal failure were induced
by an antisense oligonucleotide targeted against the rel A transcription factor.
While, Rojanasakul suggest (id.) that oligonucleotides can have non-specific
actions and may cause toxic side effects in vivo, the examiner supplies no
evidence to demonstrate that a person of ordinary skill in the art would
reasonably expect the claimed antisense oligonucleotides to exhibit similar non-
specific actions. In our opinion, the examiner failed to provide the evidence
necessary to establish that appellant’s specification does not support appellant’s
claimed invention.
As set forth in In re Armbruster, 512 F.2d 676, 677-78, 185 USPQ 152,
153 (CCPA 1975), quoting In re Marzocchi, 439 F.2d 220, 224, 169 USPQ 367,
369-70 (CCPA 1971):
[I]t is incumbent upon the Patent Office, whenever a rejection on
this basis [lack of enablement] is made, to explain why it doubts the
truth or accuracy of any statement in a supporting disclosure and to
back up assertions of its own with acceptable evidence or
reasoning which is inconsistent with the contested statement.

For the foregoing reasons, it is our opinion that the examiner failed to provide the
evidence necessary to support his position that appellant’s disclosure does not
support the full scope of the claimed invention. Accordingly, we reverse the
rejection of claims 1-9 and 16 under 35 U.S.C. § 112, first paragraph, as being
based on an insufficient disclosure to support or enable the scope of the claimed
invention.
Appeal No. 2001-1651 Page 12
Application No. 09/238,972

THE REJECTION UNDER 35 U.S.C. § 102:
As we understand appellant’s claim grouping, claim 3 stands or falls
alone, and claim 17 stands or falls together with claim 16. Brief, pages 6-7.
Appellant, however, fails to separately argue the claims as required by 37 CFR
§ 1.192(c)(7) (1999). Accordingly, claims 3, 16 and 17 will stand or fall together.
Since all claims stand or fall together, we limit our discussion to representative
independent claim 16. 37 CFR § 1.192(c)(7) (1999).
According to the examiner (Answer, page 4), “MacLeod discloses the
CAT2 cDNA double stranded sequence identified as SEQ ID NO: 5, … and also
discloses that antisense sequences can be used to inhibit CAT2 translation….”
In response, appellant points out that the application involved in this appeal is a
continuation-in-part of 08/187,634, which is a continuation-in-part of MacLeod.
According to appellant, by reciting the continuity data on the first line of the
specification in the instant application, the instant application properly
incorporates by reference the earlier application. However, as set forth in In re
De Seversky, 474 F.2d 671, 674, 164 USPQ 144, 146-47 (CCPA 1973):
the statement that an application is a continuation-in-part, or a
continuation, or a division, or in part a continuation of another
application is in a broad sense a “reference” to the earlier
application, but a mere reference to another application, or patent,
or publication is not an incorporation of anything therein into the
application containing such reference for the purposes of the
disclosure required by 35 U.S.C. [§] 112. Likewise it does not
serve to bring a disclosure within the requirements of 35 U.S.C.
[§] 120 so as to give a later application the benefit of the filing date
of an earlier application. The later application must itself contain
the necessary disclosure. As we said in … [In re Lund, 376 F.2d
982, 989, 153 USPQ 625, 631 (CCPA 1967)],

Appeal No. 2001-1651 Page 13
Application No. 09/238,972

As the expression itself implies, the purpose of
“incorporation by reference” is to make one document
become a part of another document by referring to the
former in the latter in such a manner that it is apparent that
the cited document is part of the referencing document as if
it were fully set out therein. …
We held in Lund that the mere statement that an application is a
“continuation-in-part” does not do that.

Accordingly, we are not persuaded by appellant’s argument that simply reciting
the continuing data on the first page of the specification incorporates the
disclosure of the prior applications by reference.
We agree with appellant’s argument (Brief, page 10), that a later filed
application is entitled to the benefit of the filing date of an earlier filed application
with regard to the subject matter that is common to both applications. However,
as the examiner points out (Answer, page 9), “there was no common subject
matter, particularly antisense oligos in application 08/187,634 [now U.S. Patent
5,866,123 (‘123)], as noted by appellant[1], thereby barring applicants from
priority benefit to … [MacLeod] which was not copending with the current
application.”
Similar to the facts in this case, our appellate reviewing court explained in
In re Chu, 66 F.3d 292, 297, 36 USPQ2d 1089, 1093 (Fed. Cir. 1995):
It is elementary patent law that a patent application is entitled to the
benefit of the filing date of an earlier filed application only if the
disclosure of the earlier application provides support for the claims
of the later application, as required by 35 U.S.C. Section 112. 35
U.S.C. Section 120. Mendenhall v. Cedarapids Inc., 5 F.3d 1557,
1566, 28 USPQ2d 1081, 1088-89 (Fed. Cir. 1993) (“A patentee
cannot obtain the benefit of the filing date of an earlier application
where the claims in issue could not have been made in the earlier
application.”), cert. denied, 114 S. Ct. 1540 (1994); see also Litton

1 According to appellant (Brief, page 10), “U.S. Patent Application Ser. No. 08/187,634 does not
discuss antisense oligonucleotides directed against CAT2 mRNA….”
Appeal No. 2001-1651 Page 14
Application No. 09/238,972

Sys., Inc. v. Whirlpool Corp., 728 F.2d 1423, 1438, 221 USPQ 97,
106 (Fed. Cir. 1984) (discussing filing dates of CIP applications).
Thus, Chu is entitled to the benefit of the Doyle patent filing date
only if the Doyle patent discloses the subject matter now claimed
by Chu. This, however, is admitted by Chu not to be the case. In
fact, Chu states that “the invention as now claimed[ ] was not
described in the [Doyle] patent.” … Accordingly, Chu cannot
obtain the benefit of the Doyle patent filing date for these claims
and the Doyle patent was properly relied on as prior art.

Accordingly, in order for the instant application to be entitled under 35 U.S.C.
§ 120 to the filing date of an earlier application in the chain of applications it is
part of, it must be shown that as to the inventions claimed there has been
“continuing disclosure through the chain of applications, without hiatus.” In re
Schneider, 481 F.2d 1350, 1356, 179 USPQ 46, 50 (CCPA 1973). Accord In re
Hogan, 559 F.2d 595, 609, 194 USPQ 527, 540 (CCPA 1977); In re Goodman,
476 F.2d 1365, 1368, 177 USPQ 574, 576 (CCPA 1973). Appellant admits on
this record that the ‘123 patent “does not discuss antisense oligonucleotides
directed against CAT2 mRNA….” Brief, page 10. Accordingly, there was no
continuing disclosure through the chain of applications.
Appellant also argues (id.), “[g]iven the disclosure of the sequence [in the
‘123 patent], the design and selection of an antisense oligonucleotide against
CAT2 mRNA was completely within range of one with ordinary skill in the art.”
However, as our appellate reviewing court held in Lockwood v. American
Airlines, Inc., 107 F.3d 1565, 1572, 41 USPQ2d 1961, 1966 (Fed. Cir. 1997):
While the meaning of terms, phrases, or diagrams in a disclosure is
to be explained or interpreted from the vantage point of one skilled
in the art, all the limitations must appear in the specification. The
question is not whether a claimed invention is an obvious variant of
that which is disclosed in the specification. Rather, a prior
Appeal No. 2001-1651 Page 15
Application No. 09/238,972

application itself must describe an invention, and do so in sufficient
detail that one skilled in the art can clearly conclude that the
inventor invented the claimed invention as of the filing date sought.

Accordingly, we do not agree with appellant’s statement (Brief, page 10), “the
specification of … [‘123] inherently provides the basis for support for antisense
oligonucleotides directed against CAT2 mRNA since the specification discloses
the gene sequence of CAT2.”
For the foregoing reasons, we affirm the rejection of claim 16 under 35
U.S.C. § 102(b) as being anticipated by MacLeod. As set for above, claims 3
and 17 fall together with claim 16.
No time period for taking any subsequent action in connection with this
appeal may be extended under 37 CFR § 1.136(a).
AFFIRMED-IN-PART

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

Appeal No. 2001-1651 Page 16
Application No. 09/238,972

Benjamin Aaron Adler
McGregor & Adler
8011 Candle Lane
Houston, TX 77071

DEA/jlb