Ex Parte Bathe et al

Board of Patent Appeals and Interferences

Jan 16, 2008

10446154 (B.P.A.I. Jan. 16, 2008)

UNITED STATES PATENT AND TRADEMARK OFFICE
____________

BEFORE THE BOARD OF PATENT APPEALS
AND INTERFERENCES
____________

Ex parte BRIGITTE BATHE, MIKE FARWICK,
ACHIM MARX, and WALTER PFEFFERLE
____________

Appeal 2007-4479
Application 10/446,154
Technology Center 1600
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Decided: January 16, 2008
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Before DEMETRA J. MILLS, LORA M. GREEN,
and RICHARD M. LEBOVITZ, Administrative Patent Judges.

GREEN, 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 26-34 and 36-43. We have jurisdiction
under 35 U.S.C. § 6(b). Claim 26 is representative of the claims on appeal,
and reads as follows:
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26. A process for the preparation of a desired L-amino acid, comprising:
fermenting modified coryneform bacteria to produce a fermentation broth,
wherein said modified coryneform bacteria produce said desired L-amino
acid and do not express the malate enzyme (mez).

The Examiner relies on the following references:
Molenaar US 2002/0028490 A1 Mar. 7, 2002
Pompejus WO 01/00844 A2 Jan. 4, 2001

ExPASy –http://us.expasy.org/cgi-bin/nicezyme.p1? 1.1.1.39
(accessed November 17, 2005)

ExPASy –http://us.expasy.org/cgi-bin/enzyme-search-ec (accessed
November 16, 2005)

Bernard R-Glick et al., “Molecular Biotechnology-Principles and
Applications of Recombinant DNA,” Microbial Synthesis of Commercial
Products, 168-170.

We affirm.

DISCUSSION
Claims 26-31, 34, and 36-43 stand rejected under 35 U.S.C. § 102(b)
as being anticipated by Pompejus. As Appellants do not argue the claims
separately, they stand or fall together. We thus focus our analysis on
independent claim 26.
Pompejus is cited for teaching the production of a desired compound,
such as an L-amino acid, using Corynebacterium glutamicum, with an
altered SMP (sugar metabolism and oxidative phosphorylation) gene
(Answer 4).
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In order for a prior art reference to serve as an anticipatory reference,
it must disclose every limitation of the claimed invention, either explicitly or
inherently. In re Schreiber, 128 F.3d 1473, 1477 (Fed. Cir. 1997). We
agree with the Examiner that Pompejus anticipates the subject matter of
claim 26, and the rejection is affirmed.
Appellants argue that “Pompejus does not disclose a process for
producing amino acids in which the activity of the malate enzyme is
attenuated and believe that the Examiner has engaged in an impermissible
hindsight reconstruction of the invention claimed.” (Br. 8.) According to
Appellants, “combining a laundry list of genes and a laundry list of possible
functions is not a disclosure sufficiently specific to meet the requirements of
35 USC § 102. More specifically, Appellants submit that the reference does
not associate a particular function with the mez gene that would lead one of
skill in the art to the conclusion that reducing the expression of this gene
should increase the fermentative production of amino acids.” (Id. at 8-9.)
Appellants assert further that Pompejus is not directed to methods of
amino acid production, but rather to the bacterial production of fine
chemicals, and thus the genes discloses by Pompejus could have a wide
variety of functions rather than contributing to the production of amino acids
(id. at 9). Appellants also assert that Pompejus does not disclose how the
disclosed genes, including the mez gene, should be altered, except for
teaching that they may be engineered to decrease activity, increase activity,
or left unchanged (id.). Thus, according to Appellants,
Pompejus could just as easily reach the conclusion that
attenuating the activity of this gene would decrease bacterial
amino acid production or that it would have no effect on amino
acid production at all. The Examiner has picked out the
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possibility of attenuation increasing activity and concluded that
Appellants’ claims are anticipated but this is clearly a hindsight
reconstruction of the invention. The actual teaching of
Pompejus is that the attenuation of mez might or might not
increase or decrease amino acid production. Appellants submit
that this is really not a teaching at all and it is not sufficiently
specific to constitute an anticipation of Appellants' claims.

(Id.)
Appellants argue further that the only suggestion of activity for the
mez gene is the designation of “EMB pathway.” (Id. at 10.) However,
Appellants assert, the EMB (Embden Myerhof pathway) is an anaerobic
pathway in which glucose is converted to lactic acid, and is thus not directly
involved in the synthesis of amino acids by the bacteria, and thus one of
ordinary skill would not conclude that eliminating mez would increase
amino acid production (id.). According to Appellants, the test of whether
Pompejus is anticipatory is whether “if one of skill in the art were to be
handed a copy of Pompejus and asked what it teaches concerning the effect
of attenuating the mez gene on amino acid production, they would have to
answer that it teaches that attenuation should increase production.” (Id.)
Appellants assert that the answer to that question would be that “Pompejus
teaches that attenuation of mez might increase amino acid production,
decrease amino acid production or have no effect at all.” (Id.) Appellants
conclude “the reference leaves open all possibilities and broad, nonspecific
generalizations of the type present are insufficient to constitute an
anticipation.” (Id.)
Pompejus teaches that the Corynebacterium glutamicum bacterium “is
commonly used in industry for the large-scale production of a variety of fine
chemicals.” (Pompejus, p. 2, ll. 24-25.) Pompejus teaches further that the
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“invention provides novel nucleic acid molecules which encode proteins
referred to herein as SMP proteins, which are capable of, for example,
performing a function involved in the metabolism of carbon compounds
such as sugars and the generation of energy molecules by processes of
oxidative phosphorylation in Corynebacterium glutamicum.” (Id. at 5, ll. 7-
11.)
Pompejus teaches C. glutamicum in which a SMP gene of interest has
been introduced or altered (id. at 7, ll. 13-14). Alterations include disruption
of the gene by homologous recombination, so that the gene no longer
encodes a functional protein, or other alterations such as mutations,
deletions, or inversions, wherein the gene still encodes a functional SMP
protein (id. at 5, ll. 17-21; id. at 46, ll. 18-29). “In a preferred embodiment,
the microorganism is also utilized for the production of a desired compound,
such as an amino acid, with lysine being particularly preferred.” (Id. at 7, ll.
27-29.) Table 1 (id. at 59-71) teaches SMP genes, of which malate enzyme
(id. at 60-61) is admittedly listed with many other genes.
Thus, what is taught by Pompejus is alteration of a SMP gene, such as
the gene for malate enzyme, wherein the gene no longer produces a
functional protein, or wherein the attenuated gene still produces a functional
protein, in the production of a fine chemical, with the L-amino acid, L-lysine
being especially preferred. Note that a reference need not have described an
actual reduction to practice of an invention in order to serve as an
anticipatory reference. In re Siveramakrishnan, 673 F.2d 1383, 1384,
(CCPA 1982); In re Donohue, 766 F.2d 531, 533, (Fed. Cir. 1985).
Malate enzyme does occur in a long list of SMP proteins, but that
does not obviate the fact that malate enzyme was a specifically disclosed
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species of SMP protein. See Nicholas v. Perricone v. Medicis
Pharmaceutical Corp., 432 F.3d 1368, 1376-77, (Fed. Cir. 2005) (finding
that a composition comprising two different ingredients, ascorbyl palmitate
and tocopherol, in a listing of additional possible skin benefit ingredients,
constituted anticipatory prior art). In addition, Pompejus teaches both
knocking out the activity of the malate enzyme, as well as attenuating its
activity. Just because it teaches both, however, does not obviate the fact that
it anticipates knocking out the malate activity. As to the number of fine
chemicals discosed by Pompejus that may be produced by C. glutamicum,
Pompejus does teach that production of L-amino acids, particularly L-lysine,
is particularly preferred.
Finally, we agree with Appellants that Pompejus does not teach
whether the production of the L-amino acid would be increased, decreased,
or unaffected by knocking out the function of the malate enzyme. Claim 26,
however, does not require any level of L-amino acid production.
Thus, we do not agree with Appellants that the test of whether
Pompejus is anticipatory is whether if one of skill in the art were to be
handed a copy of Pompejus and asked what it teaches concerning the effect
of attenuating the mez gene on amino acid production, they would have to
answer that it teaches that attenuation should increase production. Rather,
the test is whether Pompejus teaches a method for the preparation of a
desired L-amino acid, comprising: fermenting modified coryneform bacteria
to produce a fermentation broth, wherein said modified coryneform bacteria
produce said desired L-amino acid and do not express the malate enzyme.
For the reasons set forth above, we find that it does.
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Appellants argue further that the “Pompejus reference issued in the
US as patent 6,822,084 and the statements made by the Examiner reviewing
that case fully support the arguments presented herein and in Appellants’
Appeal Brief.” (Reply Brief 8). First, the argument is not properly before us
as it was not first presented in the Appeal Brief. Notwithstanding that fact,
the section of the Final Action from the prosecution of the ’084 patent have
been considered, but are not found to be dispositive on the issues in the
instant Appeal. Each application is examined on its own merits, and one
section of a Final Office Action taken from the prosecution of an issued U.S.
Patent does not provide a full picture of the prosecution and eventual
allowance of the ’084 patent.

Claims 26-34 and 36-43 stand rejected under 35 U.S.C. § 103(a) as
being obvious over the combination of Pompejus, Molenaar, and Glick.
Again, as Appellants do not argue the claims separately, they stand or fall
together, and we again focus our analysis on idependent claim 26.
First, as we have already found that claim 26 is anticipated by
Pompejus, and as anticipation is the epitome of obviousness, the rejection is
affirmed for the reasons set forth above.
Moreover, Appellants reiterate their arguments as to Pompejus, and
further assert that Molenaar and Glick do not remedy the deficiencies of
Pompejus (Br. 11). Those arguments are not found to be convincing for the
reasons set forth above with respect to the anticipation rejection over
Pompejus.
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CONCLUSION
In summary, because we find that the Examiner has set forth a prima
facie case of unpatentability that has not been adequately rebutted by
Appellants, the rejections of record are affirmed.
No time period for taking any subsequent action in connection with
this appeal may be extended under 37 C.F.R. § 1.136(a).

AFFIRMED

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