Ex Parte Laughon

Board of Patent Appeals and Interferences

Oct 27, 2009

09810385 (B.P.A.I. Oct. 27, 2009)

UNITED STATES PATENT AND TRADEMARK OFFICE
__________

BEFORE THE BOARD OF PATENT APPEALS
AND INTERFERENCES
__________

Ex parte ALLEN S. LAUGHON
__________

Appeal 2008-005835
Application 09/810,385
Technology Center 1600
__________

Decided: October 27, 2009
__________

Before DONALD E. ADAMS, DEMETRA J. MILLS, and ERIC GRIMES,
Administrative Patent Judges.

MILLS, Administrative Patent Judge.

DECISION ON APPEAL

This is an appeal under 35 U.S.C. § 134. The Examiner has rejected
the claims for new matter and indefiniteness. We have jurisdiction under 35
U.S.C. § 6(b).

Appeal 2008-005835
Application 09/810,385

STATEMENT OF CASE
The following claim is representative.
9. A method for identifying compounds that directly interact with a
Smad protein or a DNA-binding Smad corepressor protein to prevent
protein-protein or protein-DNA interactions required for repression of
transcription from genes induced by TGF-β, activin or bone morphogenetic
protein signaling in cells comprising:
(a) detecting in a cell a first level of transcription of a reporter with a
promoter which is regulated by a TGF-β, activin or bone morphogenetic
protein signal, wherein said cell co-expresses interacting proteins comprising
a Smad protein, a DNA-binding Smad co-repressor protein and a CtBP
protein;
(b) contacting said cell with a test compound;
(c) detecting a second level of transcription of the reporter in the cell
after addition of the test compound; and
(d) comparing the first level with the second level, wherein a decrease
in the level of repression of transcription of the reporter in said cell after
addition of the test compound is indicative of the ability of the test
compound to interfere with transcriptional repression of genes induced by a
TGF-β, activin or bone morphogenetic protein signal in cells.

Grounds of Rejection
1. Claims 9-12 are rejected under 35 U.S.C. § 112, first paragraph, as failing
to comply with the written description requirement for containing new
matter.
2. Claims 9-12 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 applicant regards as the invention.

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New Matter Rejection
1. Claims 9-12 are rejected under 35 U.S.C. § 112, first paragraph, as
failing to comply with the written description requirement for containing
new matter.
FINDINGS OF FACT
1. “The TGF-β superfamily is one of the largest groups of polypeptide
growth and differentiation factors. A variety of structural and functional
criteria have been used to group the superfamily into three classes: (1) TGF-
β's; (2) activins; and (3) bone morphogenetic proteins (BMPs).” (Spec. 1.)
2. “TGF-β and its related factors, including activin, bone morphogenetic
proteins (BMPs), and their Drosophila counterpart, decapentaplegic, each
signal to their target cells by a unique signaling cascade activated by ligand-
induced serine-threonine kinase receptor complex formation” (Spec. 2).
3. “TGF-β signaling pathways regulate transcription in cells by activating
Smad proteins. Activated Smad complexes translocate to the nucleus where
they activate target genes in coordination with interacting co-factors.”
(Spec. 7.)
4. “It is now well established that TGF-β signaling pathways switch target
genes on through the activities of Smad proteins. These cytosolic proteins
are recruited and phosphorylated by the TGF-β, activin, or BMP receptor
complexes.” (Spec. 2, emphasis added.)
5. “[A]lthough much is now known about how TGF-β pathways switch
genes on, little is known about how gene can be switched off. There are
examples of such negative regulation in vertebrates and in model organisms
such as C. elegans and Drosophila.” (Spec. 2.)
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6. “Negative regulation by Smad proteins was also shown in Drosophila,
where the Drosophila BMP4 [bone morphogenic protein] homolog,
decapentaplegic (dpp), was shown to activate its targets by repressing
expression of a novel repressor known as Brinker.” (Spec. 2-3.)
7. “Ectopically expressed Brinker was able to repress BMP targets in
frog embryos as well, indicating that this double negative mechanism is
likely to operate in vertebrates as well as in Drosophila.” (Spec. 3.)
8. “Using a Drosophila system, it has also been found that signaling by the
TGF-β family member, Dpp, is negatively regulated by the brinker (brk)
gene. . . . Like all TGF-β pathways, the Dpp pathway activates the Smad
protein Mad, which forms a complex with its partner Smad, Medea, and
regulates nuclear targets such as vg, Ubx, and tinman (tin). . . . The data now
show that the brinker protein (Brk) binds and represses the Dpp response
elements of vg and Ubx.” (Spec. 10-11.)
9. The Specification states that “the present invention describes the
interaction between Smad proteins and the general co-repressor dCtBP and
shows how this interaction provides a mechanism for the ability of activated
Smads to directly repress transcription in response to signaling” (Spec. 4).
10. The Specification states that
[w]ith identification of the mechanism of . . . direct interaction
of Smad proteins with co-repressors, assays can be developed,
for example to identify proteins or small molecules tha interact
with Smad proteins to prevent interaction of CtBP with Smads
or with DNA-binding co-repressors . . . , or of formation of a
DNA-bound complex containing Smads, CtBP and DNA-
binding co-repressors, and thus prevent repression of genes that
are negatively regulated by TGFβ signaling pathways.
(Spec. 14.)
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11. The Specification, as filed, on page 4 states that:
An object of the present invention is a method for
identifying compounds that directly interact with Smad
proteins, or with Smad co-repressors, to prevent protein-
protein or protein-DNA interactions required for transcriptional
repression in response to a TGFβ, activin, or bone
morphogenetic protein signal which comprises determining
changes in the level of transcription in cells, before and after
addition of a test compound, wherein a decrease in the level of
transcriptional repression is indicative of the ability of the test
compound to interact with Smad proteins or Smad co-
repressors to interfere with transcriptional repression that
otherwise would occur in response to signaling by a TGFβ,
activin or bone morphogenetic protein.

See also original claims 1 and 6.
12. The Declaration of Laughon states that the components, including
promoters, used in the claimed assay were known at the time of filing of the
'385 application and are those described in the ‘385 application. Laughon
states:
The components used in the assay were known at the time of
filing of the '385 application and are those described in the ‘385
application and depicted in Figure 6, namely Mad and Medea as
Smad proteins, Shn [schnurri] as the DNA-binding Smad co-
repressor protein, dCtBP, and lacz as the re-porter, the
expression of which is controlled by the brk promoter, a direct
target of Mad/Medea and schnurri (see abstract of Muller et al.
(20031 Cell 113 :221-- 233; Exhibit A) .

… In this assay, repression of the brk-lac2 reporter is caused
by cotransfection of a plasmid that expresses TkvQD, an
activated form of the type I Dpp receptor. Cotransfection with a
plasmid expressing ElA blocks this repression by inhibiting
CtBP. Accordingly, having used the well-known assay
components and guidance provided in the specification for
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carrying out the method of the ‘385 application, we have
successfully identified a compound that interferes with
transcriptional repression of genes induced by a TGF-13 [sic,
β], activin or bone morphogenetic protein signal in cells.

(Laughon Declaration, pages 1-2.)
13. The Examiner finds that,
At most the passage contained within page 14, line 11
and page 15, line 12 mentions TGF-β- dependent reporter
expression and one of ordinary skill in the art could assume that
expression must be directed by a TGF-β promoter, but as noted
in the FAOM mailed June 14, 2006 that may not happen under
the exclusivity of the TGF-β promoter.

(Ans. 3-4.)

14. The Examiner finds that
This section of the specification [page 14, line 11 to page 15,
line 12] does not make mention of the activin or bone
morphogenetic protein signal influencing transcription. Pages 9
and 10 of the specification do not exemplify the claimed
method and pages 1-3 in no form or fashion seem to
contemplate the claimed method implementing activin or a
bone morphogenetic protein signal to regulate a promoter,
which in turn directs transcription.

(Id. at 4.)

15. The Examiner finds that, “at best, one of ordinary skill in the art can
assume there is a TGF-β promoter involved in the claimed method, clearly
there is no support for activin or bone morphogenetic protein signal
regulating a promoter.” (Id.)
16. The Examiner finds that “none of the recited passages [in the
Specification] list the reporter with a TGF-β-dependent promoter or activin
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or bone morphogenetic protein signal within cells expressing specifically
interacting proteins with the detection of transcription and the comparison
between levels of transcription at precise points.” (Ans. 4.)

PRINCIPLES OF LAW
When new matter is added to the claims, the proper course of action is
to reject said claims for failing to satisfy the written description requirement
of § 112, first paragraph. In re Rasmussen, 650 F.2d 1212, 1214 (CCPA
1981)(“The proper basis for rejection of a claim amended to recite elements
thought to be without support in the original disclosure, therefore, is § 112,
first paragraph ...”). The purpose of the written description requirement is to
“ensure that the scope of the right to exclude, as set forth in the claims, does
not overreach the scope of the inventor's contribution to the field of art as
described in the patent specification.” Reiffin v. Microsoft Corp., 214 F.3d
1342, 1345 (Fed. Cir. 2000). To that end, to satisfy the written description
requirement, the inventor “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” [first emphasis added]. Vas-Cath Inc. v.
Mahurkar, 935 F.2d 1555, 1563-64 (Fed. Cir. 1991). “One shows that one is
'in possession' of the invention by describing the invention, with all its
claimed limitations” [emphasis in original]. Lockwood v. American Airlines,
Inc., 107 F.3d 1565, 1572 (Fed. Cir. 1997).
We further point out that it is not necessary for the specification to
describe the claimed invention ipsis verbis; all that is required is that it
reasonably convey to those skilled in the art that, as of the filing date sought,
the inventor was in possession of the claimed invention. Union Oil Co. of
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California v. Atlantic Richfield Co., 208 F.3d 989, 997 (Fed. Cir. 2000);
Vas-Cath Inc. v. Mahurkar, 935 F.2d at 1563-64; In re Gosteli, 872 F.2d
1008,1012 (Fed. Cir. 1989); In re Edwards, 568 F.2d 1349, 1351-52 (CCPA
1978). The test for determining compliance with the written description
requirement is whether the disclosure of the application as originally filed
reasonably conveys to the artisan that the inventor had possession at that
time of the later claimed subject matter, rather than the presence or absence
of literal support in the specification for the claim language. See Vas-Cath,
Inc. v. Mahurkar, 935 F.2d at 1563-64 and In re Kaslow, 707 F.2d 1366,
1375 (Fed. Cir. 1983). Furthermore, claim language must be analyzed “not
in a vacuum, but always in light of the teachings of the prior art and of the
particular application disclosure as it would be interpreted by one possessing
the ordinary level of skill in the pertinent art.” In re Moore, 439 F.2d 1232,
1235 (CCPA 1971). [Emphasis added.]

ISSUE
The issue is: Has Appellant demonstrated error in the Examiner’s new
matter rejection or is there support in the application as filed for the claim 9
language “a promoter which is regulated by a TGF-β, activin or bone
morphogenetic protein signal, wherein said cell co-expresses interacting
proteins comprising a Smad protein, a DNA binding Smad co-repressor
protein and a CtBP protein?”

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ANALYSIS
The Examiner finds that
This section of the specification [page 14, line 11 and page 15,
line 12] does not make mention of the activin or bone
morphogenetic protein signal influencing transcription. Pages 9
and 10 of the specification do not exemplify the claimed
method and pages 1-3 in no form or fashion seem to
contemplate the claimed method implementing activin or a
bone morphogenetic protein signal to regulate a promoter,
which in turn directs transcription.

(Ans. 4.) The Examiner finds that, “at best, one of ordinary skill in
the art can assume there is a TGF-β promoter involved in the claimed
method, clearly there is no support for activin or bone morphogenetic
protein signal regulating a promoter.” (Id.)
We do not agree with the Examiner’s findings of fact and do not
find, on the evidence before us, that the Examiner has established a prima
facie case of new matter.
The Specification, as filed, on page 4 states that:
An object of the present invention is a method for
identifying compounds that directly interact with Smad
proteins, or with Smad co-repressors, to prevent protein-
protein or protein-DNA interactions required for transcriptional
repression in response to a TGFβ, activin, or bone
morphogenetic protein signal which comprises determining
changes in the level of transcription in cells, before and after
addition of a test compound, wherein a decrease in the level of
transcriptional repression is indicative of the ability of the test
compound to interact with Smad proteins or Smad co-
repressors to interfere with transcriptional repression that
otherwise would occur in response to signaling by a TGFβ,
activin or bone morphogenetic protein.

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See also original claims 1 and 6. (FF 11.) This passage of the Specification
indicates that there is transcriptional repression in response to a TGF-β,
activin, or bone morphogenetic protein signal. Thus, the original
Specification supports transcriptional repression in response to a TGF-β,
activin, or bone morphogenetic protein signal. In addition, the Specification
states that Drosophila BMP4 (a bone morphogenic protein homolog),
decapentaplegic (dpp), was shown to activate its targets by repressing
expression of a novel repressor known as Brinker. (FF 6.) Dr. Laughon
further clarifies that the promoter regulated by dpp, brk, is known in the art
and described in the application.
The components used in the assay were known at the time of
filing of the '385 application and are those described in the ‘385
application and depicted in Figure 6, namely Mad and Medea as
Smad proteins, Shn as the DNA-binding Smad co-repressor
protein, dCtBP, and lacz as the re-porter, the expression of
which is controlled by the brk promoter, a direct target of
Mad/Medea and schnurri (see abstract of Muller et al. (20031
Cell 113 :221-- 233; Exhibit A).

(Laughon Declaration, 2, FF12.) Thus, the Specification as filed discloses a
promoter which is regulated by a BMP, the brk promoter, which is a target
of the BMP, Dpp.
Appellant further contends that
Appellant exemplifies reporter constructs containing
promoters (e.g., the wingless promoter), which are regulated by
such signals in cell based assays, wherein cells of the assays co-
express interacting proteins comprising a Smad protein, a
DNA-binding Smad co-repressor protein and a CtBP protein.
See pages 9 and 10.

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Application 09/810,385

(App. Br. 7-8.) We agree with Appellant that the Specification’s examples
using proteins in the TGF-β superfamily that are not TGF-β itself, is
evidence that the Specification’s reference to “TGF-β signaling pathways”
(e.g., on pages 14-15) generically encompasses signaling pathways of the
TGF-β superfamily, including activin and bone morphogenetic proteins.
We find that Appellant has shown support in the original disclosure
for promoters regulated by bone morphogenetic protein, and that such
promoters are known in the art. See Laughon Declaration, FF12. We find
that the Examiner has provided no evidence that persons of skill in the art
would understand that the claimed promoter which is regulated by a TGF-β,
activin or bone morphogenetic protein signal was not disclosed in the
original specification. The new matter rejection is reversed.

CONCLUSION OF LAW
Appellant has demonstrated error in the Examiner’s new matter
rejection or is there support for the claim 9 language “a promoter which is
regulated by a TGF-β, activin or bone morphogenetic protein signal.” The
new matter rejection is reversed.

Indefiniteness
2. Claims 9-12 stand 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 applicant regards as the invention.
ISSUE
The Examiner finds that claim 9, line 3 cites a “bone morphogenetic
protein signal.” The Examiner concludes that it is not clear what this signal
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is and how it regulates a promoter. The Examiner thus finds that the metes
and bounds cannot be determined. (Ans. 5.)
Appellant contends that one of ordinary skill in the art would clearly
understand what is meant by a TGF-β, activin or bone morphogenetic
protein signal. (App. Br. 8.)
Issue: Has the Examiner established that one of ordinary skill in the
art would not have understood the phrase “bone morphogenetic protein
signal?”

FINDINGS OF FACT
17. Claim 9 recites “a TGF-β, activin or bone morphogenetic protein signal”
(Claim 9).
PRINCIPLES OF LAW
One of the purposes of 35 U.S.C. § 112, second paragraph,
[I]s to provide those who would endeavor, in future enterprise,
to approach the area circumscribed by the claims of a patent,
with the adequate notice demanded by due process of law, so
that they may more readily and accurately determine the
boundaries of protection involved and evaluate the possibility
of infringement and dominance.

In re Hammack, 427 F.2d 1378, 1382 (CCPA 1970) (citations omitted). As
set forth in Amgen, Inc. v. Chugai Pharmaceutical Co., Ltd., 927 F.2d 1200,
1217 (Fed. Cir. 1991):
The statute requires that “[t]he specification shall
conclude with one or more claims particularly pointing out and
distinctly claiming the subject matter which the applicant
regards as his invention.” A decision as to whether a claim is
invalid under this provision requires a determination whether
those skilled in the art would understand what is claimed. See
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Shatterproof Glass Corp. v. Libbey-Owens Ford Co., 758 F.2d
613, 624, 225 USPQ 634, 641 (Fed. Cir. 1985) (Claims must
“reasonably apprise those skilled in the art” as to their scope
and be “as precise as the subject matter permits.”).

Furthermore, claim language must be analyzed “not in a vacuum, but
always in light of the teachings of the prior art and of the particular
application disclosure as it would be interpreted by one possessing the
ordinary level of skill in the pertinent art.” In re Moore, 439 F.2d 1232,
1235 (CCPA 1971).
“[A]mbiguity in claim scope is at the heart of the definiteness
requirement of 35 U.S.C. § 112, ¶ 2.” Amgen Inc. v. Hoechst Marion
Roussel, Inc., 314 F.3d 1313, 1342 (Fed. Cir. 2003).

ANALYSIS
The Examiner finds that claim 9, line 3, cites a “bone morphogenetic
protein signal.” The Examiner finds that it is not clear what this signal is
and how it regulates a promoter. The Examiner thus finds that the metes and
bounds cannot be determined. (Ans. 5.)
The Specification, as filed, on page 4 states that:
An object of the present invention is a method for
identifying compounds that directly interact with Smad
proteins, or with Smad co-repressors, to prevent protein-
protein or protein-DNA interactions required for transcriptional
repression in response to a TGFβ, activin, or bone
morphogenetic protein signal which comprises determining
changes in the level of transcription in cells, before and after
addition of a test compound, wherein a decrease in the level of
transcriptional repression is indicative of the ability of the test
compound to interact with Smad proteins or Smad co-
repressors to interfere with transcriptional repression that
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Application 09/810,385

otherwise would occur in response to signaling by a TGFβ,
activin or bone morphogenetic protein.

See also original claims 1 and 6. (FF7.) Thus the Specification indicates
that a decrease in the level of transcriptional repression is indicative of the
ability of the test compound to interact with Smad proteins or Smad co-
repressors to interfere with transcriptional repression that otherwise would
occur in response to signaling by a TGFβ, activin or bone morphogenetic
protein, in other words a TGFβ signal, an activin signal or bone
morphogenetic protein signal.
We do not find that the Examiner has established a prima facie case of
claim indefiniteness. The Examiner has provided no evidence why one of
ordinary skill in the art would not have understood this phrase.

CONCLUSION OF LAW
The Examiner has not established that one of ordinary skill in the art
would not have understood the phrase “bone morphogenetic protein signal.”

REVERSED

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