**United States Court of Appeals for the Federal Circuit**

03-1327

(Serial No. 08/485,129)

IN RE DAVID WALLACH, HARTMUT ENGELMANN,

DAN ADERKA, DANIELA NOVICK, and MENACHEM RUBINSTEIN

[Roger L. Browdy]{.underline}, Browdy and Neimark, P.L.L.C., of
Washington, DC, argued for appellants.

[Mary L. Kelly]{.underline}, Associate Solicitor, Office of the
Solicitor, United States Patent and Trademark Office, of Arlington,
Virginia, argued for the Director of the U.S. Patent and Trademark
Office. With her on the brief were [John M. Whealan]{.underline},
Solicitor; and [Raymond T. Chen]{.underline}, Associate Solicitor. Of
counsel were [Stephen Walsh]{.underline} and [William
LaMarca]{.underline}, Associate Solicitors.

Appealed from: United States Patent and Trademark Office

Board of Patent Appeals and Interferences

#### United States Court of Appeals for the Federal Circuit

03-1327

(Serial No. 08/485,129)

In re DAVID WALLACH, HARTMUT ENGELMANN,

DAN ADERKA, DANIELA NOVICK and MENACHEM RUBINSTEIN

\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_

DECIDED: August 11, 2004

\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_

Before MAYER, [Chief Judge]{.underline}, LOURIE and GAJARSA, [Circuit
Judges]{.underline}.

LOURIE, [Circuit Judge]{.underline}.

David Wallach, Hartmut Engelmann, Dan Aderka, Daniela Novick, and
Menachem Rubinstein (collectively, "Appellants") appeal from the
decision of the United States Patent and Trademark Office ("PTO") Board
of Patent Appeals and Interferences affirming the rejection of claims
11-13, 35-38, 43, 44, 46-49, 51-54, 56-61, 63, and 64 of United States
patent application 08/485,129 under the written description requirement
of 35 U.S.C. § 112. [In re Wallach]{.underline}, Appeal No. 2002-1363
(Bd. Pat. Apps. & Interfs. Dec. 26, 2002). We affirm.

BACKGROUND

In the 1980s, Appellants apparently discovered two specific proteins
isolated from human urine that, among other things, selectively inhibit
the cytotoxic effect of tumor necrosis factor ("TNF"). They named the
compounds TNF binding proteins I & II ("TBP-I" and "TBP-II"). After
obtaining a partial amino acid sequence of the N-terminal portion of
TBP-II and determining that the complete protein has a molecular weight
of about 30 kilodaltons ("kDa") when measured by sodium dodecyl sulfate
polyacrylamide gel electrophoresis ("SDS-PAGE") under reducing
conditions, Appellants filed a patent application including,
[inter]{.underline} [alia]{.underline}, claims directed to proteins
having that molecular weight and partial sequence ([i.e.]{.underline},
threonine-proline-tyrosine-alanine-proline-glutamic acid-proline-glycine-serine-threonine,
or "Thr-Pro-Tyr-Ala-Pro-Glu-Pro-Gly-Ser-Thr") and having the ability to
inhibit the cytotoxic effect of TNF. Appellants' application also
included claims to isolated DNA molecules that encode the claimed
proteins. The PTO issued a restriction requirement and Appellants filed
divisional applications. The claims directed to the proteins having the
stated partial sequence are currently involved in an interference
proceeding and are not at issue here. The claims at issue, those
directed to the DNA, were rejected under § 112 "as based on a
specification which does not provide an adequate written description of
the claimed invention." [Wallach]{.underline}, slip op. at 2. After
several unsuccessful attempts to traverse that rejection, Appellants
appealed to the Board.

Citing this court's decisions in [Amgen, Inc. v. Chugai Pharmaceutical
Co.]{.underline}, 927 F.2d 1200 (Fed. Cir. 1991), [Fiers v.
Revel]{.underline}, 984 F.2d 1164 (Fed. Cir. 1993), and [Regents of the
University of California v. Eli Lilly & Co.]{.underline}, 119 F.3d 1559
(Fed. Cir. 1997), the Board affirmed the examiner's rejection. In
particular, the Board held that "(1) applicants do not describe the
genetic material sought to be patented in claim 11 with sufficient
specificity in their specification; and (2) the examiner did not err in
finding that claim 11 is based on a specification which does not provide
adequate, written descriptive support for the claimed subject matter."
[Wallach]{.underline}, slip op. at 8-9.[^1]

Appellants now appeal. We have jurisdiction pursuant to 28 U.S.C.
§ 1295(a)(4)(A).

DISCUSSION

Claim 11 of the '129 application reads as follows:

> 11\. An isolated DNA molecule comprising a contiguous nucleotide
> sequence coding for a protein consisting of naturally occurring human
> Tumor Necrosis Factor (TNF) Binding Protein II, herein designated
> TBP-II, said TBP-II including the amino acid sequence:
> Thr-Pro-Tyr-Ala-Pro-Glu-Pro-Gly-Ser-Thr in the portion of the protein
> sequenced by N-terminal sequence analysis, said protein having the
> ability to inhibit the cytotoxic effect of TNF, wherein said naturally
> occurring TBP-II protein is the same as that protein having the
> ability to inhibit the cytotoxic effect of TNF which, after being
> purified by subjecting a crude protein recovered from a dialyzed
> concentrate of human urine to affinity chromatography on a column of
> immobilized TNF, elutes from a reversed-phase high pressure liquid
> chromatography column as a single peak in a fraction corresponding to
> about 31% acetonitrile and shows a molecular weight of about 30 kDa
> when measured by SDS-PAGE under reducing conditions.

On appeal, Appellants argue that the PTO has effectively conceded that
the TBP-II protein, which the claimed isolated DNA encodes, is
sufficiently described in the specification to comply with § 112,
because the claims of United States patent application 07/930,443, of
which the '129 application is a division (which, by definition, has the
same specification), have been allowed but for their involvement in an
interference proceeding. According to Appellants, those claims do not
differ in substance from the present claims except insofar as they are
directed to a partial protein sequence, rather than to the DNA sequences
encoding the protein. Appellants contend that that is not a meaningful
distinction, because the genetic code is based on an unequivocal
correspondence between amino acids and encoding DNA codons, and
determination of the amino acid sequence of a protein automatically puts
one in possession of all DNA sequences encoding that protein. Appellants
also argue that the complete amino acid sequence of a protein is an
inherent property of an isolated protein that has been fully
characterized by partial amino acid sequence and other characteristics,
and that the complete amino acid sequence of a protein therefore puts
one in possession of all DNA sequences encoding it. Therefore, according
to Appellants, the specification establishes that the present inventors
were in fact in possession of the entire claimed genus of DNA sequences
at the time the application was filed.

Appellants also argue that this case is distinguishable from past
written description cases such as [Amgen v. Chugai]{.underline} and
[Fiers]{.underline}, because Appellants have provided an actual amino
acid sequence that is encoded by the claimed DNA, not simply the name of
the protein and a statement that the DNA can be obtained by reverse
transcription. Appellants contend that this case is also distinguishable
from [Lilly]{.underline} because the inventors here are not attempting
to claim DNA molecules encoding a plurality of unknown proteins from
various species having no common features, but only those encoding the
single protein sequence that is actually set forth in the specification.
Finally, Appellants argue that, because there is a known correlation
between the function ([i.e.]{.underline}, encoding a specified amino
acid sequence) and structure, this is the quintessential example of the
sort of functional description permitted by § 112 in view of our
decision in [Enzo Biochem, Inc. v. Gen-Probe Inc.]{.underline}, 296 F.3d
1316 (Fed. Cir. 2002). Appellants argue that our recent decision in
[Amgen Inc. v. Hoechst Marion Roussel, Inc.]{.underline}, 314 F.3d 1313
(Fed. Cir. 2003), which issued after the Board's opinion in the present
case, reaffirmed that § 112 only requires a court to determine whether a
specification conveys to one of ordinary skill in the art as of the
filing date that the inventors invented the claimed subject matter.

The PTO responds by arguing that Appellants' specification includes
neither any actual DNA sequence within the scope of the claims nor the
complete amino acid sequence of the TBP-II protein, but only the
sequence of ten out of the 185-192 amino acids that make up the protein.
Furthermore, the PTO argues, the only disclosed function of the claimed
DNA molecules is to encode the TBP-II protein, and no information is
provided from which the claimed DNA molecules can be distinguished from
other DNA molecules. According to the PTO, the identity of the nucleic
acid encoding a protein is not an inherent property of the protein. If
Appellants' reasoning were accepted, the PTO asserts, the result would
be that the disclosure of an isolated protein would be prior art under §
102 with respect to claims directed to any nucleic acid encoding the
protein. Finally, the PTO contends, substantial evidence supports the
Board's factual finding that Appellants' specification does not
adequately describe the claimed genus of DNA molecules.

As a preliminary matter, we agree with Appellants that the state of the
art has developed such that the complete amino acid sequence of a
protein may put one in possession of the genus of DNA sequences encoding
it, and that one of ordinary skill in the art at the time the '129
application was filed may have therefore been in possession of the
entire genus of DNA sequences that can encode the disclosed partial
protein sequence, even if individual species within that genus might not
have been described or rendered obvious. [Cf.]{.underline} [In re
Deuel]{.underline}, 51 F.3d 1552 (Fed. Cir. 1995). Thus, for example,
the RNA molecules required to encode the described amino acid sequence
must necessarily have the following sequence:
ACN-CCN-UAY-GCN-CCN-GAR-CCN-GGN-(UCN or AGY)-ACN, where N is A, G, C, or
U; Y is U or C; and R is G or A. [See]{.underline} James D. Watson et
al., [Molecular Biology of the Gene]{.underline} 356-57 (3d ed. 1977),
[cited in]{.underline} '129 application. A claim to the genus of DNA
molecules complementary to the RNA having the sequences encompassed by
that formula, even if defined only in terms of the protein sequence that
the DNA molecules encode, while containing a large number of species, is
definite in scope and provides the public notice required of patent
applicants. Indeed, the PTO's Manual of Patent Examining Procedure
("MPEP") states:

> Description of a representative number of species does not require the
> description to be of such specificity that it would provide individual
> support for each species that the genus embraces. For example, in the
> molecular biology arts, if an applicant disclosed an amino acid
> sequence, it would be unnecessary to provide an explicit disclosure of
> nucleic acid sequences that encoded the amino acid sequence. Since the
> genetic code is widely known, a disclosure of an amino acid sequence
> would provide sufficient information such that one would accept that
> an applicant was in possession of the full genus of nucleic acids
> encoding a given amino acid sequence, but not necessarily any
> particular species.

MPEP § 2163.II.A.3.a.ii. (8th ed., rev. 2 2001).

Moreover, we see no reason to require a patent applicant to list every
possible permutation of the nucleic acid sequences that can encode a
particular protein for which the amino acid sequence is disclosed, given
the fact that it is, as explained above, a routine matter to convert
back and forth between an amino acid sequence and the sequences of the
nucleic acid molecules that can encode it.

Nonetheless, Appellants did not claim the nucleic acid molecules that
encode the simple protein sequence that they disclosed. Rather, they
claimed the nucleic acids encoding a protein for which they provided
only a partial sequence. Appellants concede that it is now known that
urinary TBP-II has a sequence of 185-192 amino acids. Without the
approximately 95% of the amino acid sequence that Appellants did not
disclose, we cannot say that the DNA molecules claimed in the '129
application have been described. As the MPEP explains, "disclosure of a
partial structure without additional characterization of the product may
not be sufficient to evidence possession of the claimed invention." MPEP
§ 2163.II.A.3.a.i. The Board's decision was thus consistent with its
guidance in the MPEP. Here, Appellants disclosed a partial structure and
possibly sufficient additional characterization of the TBP-II protein to
satisfy the PTO that they were in possession of the claimed subject
matter in their '443 application, but that additional characterization
contributes little, if anything, to the description of the DNA molecules
claimed in the '129 application.

Appellants argue that "\[a\]s appellants have demonstrated possession of
the TBP-II protein, appellants were also necessarily in possession of
its inherent amino acid sequence, as well as all of the DNA sequences
encoding that amino acid sequence." We disagree. Whether Appellants were
in possession of the protein says nothing about whether they were in
possession of the protein's amino acid sequence. Although Appellants
correctly point out that a protein's amino acid sequence is an inherent
property of the protein, the fact that Appellants may have isolated and
thus physically possessed TBP-II does not amount to knowledge of that
protein's sequence or possession of any of its other descriptive
properties. Appellants have not provided any evidence that the full
amino acid sequence of a protein can be deduced from a partial sequence
and the limited additional physical characteristics that they have
identified. Without that full sequence, we cannot agree with Appellants
that they were possession of the claimed nucleic acid sequences. In
[Amgen v. Chugai]{.underline}, we explained that:

> A gene is a chemical compound, albeit a complex one, and it is well
> established in our law that conception of a chemical compound requires
> that the inventor be able to define it so as to distinguish it from
> other materials, and to describe how to obtain it. Conception does not
> occur unless one has a mental picture of the structure of the
> chemical, or is able to define it by its method of preparation, its
> physical or chemical properties, or whatever characteristics
> sufficiently distinguish it. It is not sufficient to define it solely
> by its principal biological property, . . . because an alleged
> conception having no more specificity than that is simply a wish to
> know the identity of any material with that biological property.

927 F.2d at 1206. Until Appellants obtained the complete amino acid
sequence of TBP-II, they had no more than a wish to know the identity of
the DNA encoding it.

As Appellants point out, we have recognized that the written description
requirement can in some cases be satisfied by functional description.
[See, e.g.]{.underline}, [Enzo]{.underline}, 296 F.3d at 1324 ("It is
not correct, however, that all functional descriptions of genetic
material fail to meet the written description requirement.").
Nonetheless, such functional description can be sufficient only if there
is also a structure-function relationship known to those of ordinary
skill in the art. As we explained above, such a well-known relationship
exists between a nucleic acid molecule's structure and its function in
encoding a particular amino acid sequence: Given the amino acid
sequence, one can determine the chemical structure of all nucleic acid
molecules that can serve the function of encoding that sequence. Without
that sequence, however, or with only a partial sequence, those
structures cannot be determined and the written description requirement
is consequently not met. As we explained in [Enzo]{.underline}, the
[Guidelines for Examination of Patent Applications under the 35 U.S.C. §
112, ¶ 1, "Written Description" Requirement]{.underline}, 66 Fed. Reg.
1099 (Jan. 5, 2001) ("[Guidelines]{.underline}"), state that

> the written description requirement can be met by "show\[ing\] that an
> invention is complete by disclosure of sufficiently detailed, relevant
> identifying characteristics . . . [i.e.]{.underline}, complete or
> partial structure, other physical and/or chemical properties,
> [functional characteristics when coupled with a known or disclosed
> correlation between function and structure]{.underline}, or some
> combination of such characteristics." [Guidelines]{.underline}, 66
> Fed. Reg. at 1106 (emphasis added).

[Enzo]{.underline}, 296 F.3d at 1324-25 (emphasis added). Appellants
have provided no evidence that there is any known or disclosed
correlation between the combination of a partial structure of a protein,
the protein's biological activity, and the protein's molecular weight,
on the one hand, and the structure of the DNA encoding the protein on
the other.

CONCLUSION

The Board correctly affirmed the examiner's determination that the
specification of the '129 application does not provide an adequate
written description of the pending claims. Accordingly, the Board's
decision is

[AFFIRMED]{.underline}.

[^1]: The Board treated all of the appealed claims as standing or
    falling together with claim 11, pursuant to 37 C.F.R. § 1.192(c)(7),
    and decided the appeal on the basis of that claim alone.
    [Wallach]{.underline}, slip op. at 5. Appellants do not challenge
    the Board on that point, and we likewise decide this appeal only on
    the basis of that claim.