In Re Alonso

United States Court of Appeals for the Federal Circuit

2008-1079
(Serial No. 08/469,749)

IN RE KENNETH ALONSO

Jennifer A. Johnson, Finnegan, Henderson, Farabow, Garrett & Dunner, L.L.P.,
of Washington, DC, argued for appellant. With her on the brief was Susan H. Griffen.

Janet A. Gongola, Associate Solicitor, Office of the Solicitor, United States Patent
and Trademark Office, of Arlington, Virginia, argued for the Director of the United States
Patent and Trademark Office. With her on the brief was Thomas W. Krause, Associate
Solicitor. Of counsel was Sydney O. Johnson, Jr., Acting Solicitor.

Appealed from: United States Patent and Trademark Office
Board of Patent Appeals and Interferences
 United States Court of Appeals for the Federal Circuit

2008-1079
(Serial No. 08/469,749)

IN RE KENNETH ALONSO

Appeal from the United States Patent and Trademark Office, Board of Patent Appeals
and Interferences in Appeal No. 2006-2148.
__________________________

DECIDED: October 30, 2008
__________________________

Before MICHEL, Chief Judge, MAYER, Circuit Judge, and STEARNS, ∗ District Judge.

STEARNS, District Judge.

Dr. Kenneth Alonso appeals a decision of the United States Patent and

Trademark Office Board of Patent Appeals and Interferences (“Board”) sustaining in

part the examiner=s final rejection of claim 92 of U.S. Patent Application No. 08/469,749

(“’749 Application”). In its decision, the Board reversed the examiner’s rejection of claim

92 for lack of enablement and sustained the rejection as invalid for lack of adequate

written description. Ex parte Alonso, No. 2006-2148 (B.P.A.I. July 25, 2007)

(“Decision”). We affirm.

I. BACKGROUND

* Honorable Richard G. Stearns, District Judge, United States District Court
for the District of Massachusetts, sitting by designation.
 An arsenal of antibodies generated by the immune system defends the human

body against illnesses caused by bacteria and cancerous cells and other invasive

agents. Antibodies are large, Y-shaped molecules secreted by white blood cells known

as “B lymphocytes,” or “B-cells.” Antibodies are capable of binding to the surfaces of

foreign cells or other substances known as “antigens.” The specific location on the

surface of the antigen where the antibody attaches is termed the “epitope.” The arms of

the Y-shaped molecule bind to the epitope with specificity. Antibodies that bind to the

same epitope are said to have the same “idiotype.” Monoclonal antibodies (“MAbs”) are

derived from a single precursor and have a single idiotype. They are produced using

“hybridoma” (fusion) technology. A human-to-human hybridoma is created by fusing a

human tumor cell to an antibody-producing human B-cell, resulting in secretion by the

B-cell of monoclonal antibodies with identical affinity and specificity to a given epitope

on the surface of the tumor cell.

On June 6, 1995, Dr. Alonso filed the ’749 Application entitled, AMethod of

Producing Human-Human Hybridomas, The Production of Monoclonal and Polyclonal

Antibodies Therefrom, and Therapeutic Use Thereof.@ 1 The claimed invention recites a

method for treating neurofibrosarcoma, a rare cancer of the sheath of a peripheral

nerve, that uses human monoclonal antibodies targeted at a patient=s tumor. Claim 92

of the ’749 Application discloses

[a] method of treating neurofibrosarcoma in a human by administering an
effective amount of a monoclonal antibody idiotypic to the
neurofibrosarcoma of said human, wherein said monoclonal antibody is
secreted from a human-human hybridoma derived from the
neurofibrosarcoma cells.

1
Alonso claimed priority to an application he filed seven years earlier
involving similar subject matter.
2
2008-1079
 In Example 1 of the ’749 Specification, Alonso described the preparation of a

tumor cell suspension from the sample of a tumor and the subsequent sensitization of

human spleen cells. The sensitized spleen cells are fused with an immortalized cell line

(e.g., a fetal marrow line, a lymphoblastoid line, or a plasma cell line from myeloma).

The resulting cells are screened for hybridomas that secrete antibodies specifically

reactive with the sensitizing tumor cells (and non-reactive with a range of other tissues

and cell types). Example 2 disclosed the results of an experiment conducted by Alonso

in treating Melanie Brown, a patient with neurofibrosarcoma. Adult spleen cells were

sensitized with cells from Brown’s tumor. The resulting hybridoma secreted monoclonal

antibodies, which reacted with a 221 KiloDalton tumor surface antigen. The spleen line

(AS-151), the lymphoblast fusion line (BM-95), and the hybridoma (HB983) were

deposited with the American Type Culture Collection in September of 1998. The

antibody from the hybridoma line was deposited with the Food and Drug

Administration. 2

The examiner rejected claim 92 as lacking adequate written descriptive support

for the broad genus of antibodies encompassed by the claim language.

2
Alonso infused Brown with 100 mg of the antibody, and cancerous lesions
in her lungs were cleared within twenty-four hours. In addition, Brown’s brain tumor
became necrotic within seven days, and she experienced a one-month regression of
her cancer.
3
2008-1079
 Applicant is reminded that the disclosure only describes the preparation of
a single Mab produced by the hybridoma cell line HB983. However, the
claims are directed toward a much larger genus of molecules (i.e., Mabs
that bind to a neurofibrosarcoma), not a specific Mab identified by the
deposited hybridoma. . . . The crux of the rejection is whether or not
applicant has provided sufficient support for the broadly claimed genus of
therapeutic anitbodies. As set forth in the rejection, the skilled artisan
would reasonably conclude that applicant was clearly not in possession of
the claimed genus of compounds. Applicant should direct the claim
language toward the only described embodiment (e.g., a Mab produced by
hybridoma HB983).

The Board affirmed the rejection, agreeing that Alonso had not adequately described

the claimed invention because the Asingle antibody described in the Specification is

insufficiently representative to provide adequate written descriptive support for the

genus of antibodies required to practice the claimed invention.@ Decision, slip op. at 7.

II. DISCUSSION

Whether an applicant has complied with the written description requirement is a

finding of fact, to be analyzed from the perspective of one of ordinary skill in the art as of

the date of the filing of the application. Regents of the Univ. of Cal. v. Eli Lilly & Co.,

119 F.3d 1559, 1566 (Fed. Cir. 1997); Vas-Cath, Inc. v. Mahurkar, 935 F.2d 1555, 1563

(Fed. Cir. 1991). This Court reviews the Board=s factual determinations under a

substantial evidence standard. In re Gartside, 203 F.3d 1305, 1316 (Fed. Cir. 2000).

ASubstantial evidence@ is relevant evidence that Aa reasonable mind might accept as

adequate to support a conclusion.@ Id. at 1312 (citation omitted). In making the

assessment, we examine “the record as a whole, taking into account evidence that both

justifies and detracts from an agency=s decision.@ Id. That a fact finder could draw Atwo

inconsistent conclusions from the evidence does not prevent an administrative agency=s

finding from being supported by substantial evidence.@ Id. (citation omitted). Rather,

4
2008-1079
the Board=s decision must be affirmed if any Areasonable fact finder could have arrived

at the [same] decision.@ Id.

The written description requirement of 35 U.S.C. ' 112, & 1, is straightforward:

AThe specification shall contain a written description of the invention . . . .@ To satisfy

this requirement, the specification must describe the invention in sufficient detail so “that

one skilled in the art can clearly conclude that the inventor invented the claimed

invention as of the filing date sought.@ Lockwood v. Am. Airlines, Inc., 107 F.3d 1565,

1572 (Fed. Cir. 1997); see also LizardTech, Inc. v. Earth Res. Mapping, Inc., 424 F.3d

1336, 1345 (Fed. Cir. 2005); Eiselstein v. Frank, 52 F.3d 1035, 1039 (Fed. Cir. 1995).

The requirement Aserves a teaching function, as a ‘quid pro quo’ in which the

public is given >meaningful disclosure in exchange for being excluded from practicing

the invention for a limited period of time.=@ Univ. of Rochester v. G.D. Searle & Co., Inc.,

358 F.3d 916, 922 (Fed. Cir. 2004) (quoting Enzo Biochem, Inc. v. GenProbe Inc., 323

F.3d 956, 970 (Fed. Cir. 2002)). 3 The Board framed the issue raised by the ’749

Application as follows.

[W]hether the single monoclonal antibody described in the Specification is
representative of the genus of monoclonal antibodies required to practice
the claimed treatment method. That, in turn, depends on whether or not
the antibodies (and the antigens they bind) would have been expected to
vary substantially within the genus. The greater the variation in the genus,
the less representative any particular antibody would be.

Decision, slip op. at 6.

3
The requirement is rigorous, but not exhaustive: A[I]t is unnecessary to
spell out every detail of the invention in the specification; only enough must be included
to convince a person of skill in the art that the inventor possessed the invention.@
LizardTech, 424 F.3d at 1345.
5
2008-1079
 The Board properly characterized the relevant genus as the Agenus of antibodies

specific to neurofibrosarcoma cells.@ Id. A genus can be described by disclosing: (1) a

representative number of species in that genus; or (2) its Arelevant identifying

characteristics,@ such as Acomplete or partial structure, other physical and/or chemical

properties, functional characteristics when coupled with a known or disclosed

correlation between function and structure, or some combination of such

characteristics.@ Enzo, 323 F.3d at 964.

Relying principally on two scientific articles, including one authored by Alonso

himself, the Board determined that

[t]here is ample evidence of record that the specificities of antibodies
falling within the scope of the genus (and the structures of the antigens
they bind) would be expected to vary substantially. For example, Osband 4
provides evidence of a recognition in the art that considerable antigenic
Aheterogeneity of tumors both between patients and metastatic sites within
a single patient@ is to be expected. In addition, an article authored by
[Alonso] 5 acknowledges that A[t]he efficacy of antibody therapy is thought
to be related to tumor burden as well as to idiotypic change in the original
tumor.” This acknowledged heterogeneity is reflected in the goal of the
claimed method - to raise customized antibodies to possibly unique
antigens on a particular patient=s tumor.

Finally, as discussed above, for purposes of satisfying the written
description requirement, it is not enough merely to disclose a method of
making and identifying compounds capable of being used to practice the
claimed invention. That is, it is not enough to describe[] the procedure for
making a human-human hybridoma from neurofibrosarcoma, and teach
how to determine whether a given antibody, specific to a patient=s
neurofibrosarcoma, will function in the claimed method. We find that the
single antibody described in the Specification is insufficiently
representative to provide adequate written descriptive support for the
genus of antibodies required to practice the claimed invention.

4
M.E. Osband and S. Ross, Problems in the Investigational Study and
Clinical Use of Cancer Immunotherapy, 11 Immunology Today 193-95 (1990).
5
Kenneth Alonso, Human-Human Monoclonal Antibody Directed Against
Tumor Surface Antigen in the Treatment of Human Malignancy, 14 American Journal of
Clinical Oncology 463-71 (1991).
6
2008-1079
Decision, slip op. at 6-7 (internal quotation marks and citations omitted, footnotes

supplemented).

The Board=s conclusion is supported by substantial evidence. The articles relied

upon by the Board confirm the hypothesis that the antibodies required to perform

Alonso’s claimed method vary substantially in their composition. We have previously

held in a similar context that Aa patentee of a biotechnological invention cannot

necessarily claim a genus after only describing a limited number of species because

there may be unpredictability in the results obtained from species other than those

specifically enumerated.@ Noelle v. Lederman, 355 F.3d 1343, 1350 (Fed. Cir. 2004).

In another similar case, we evaluated claims directed to a method of determining

whether a drug could selectively inhibit the activity of COX-2, a cyclooxygenase thought

to be responsible for inflammation associated with arthritis. See Rochester, 358 F.3d at

917-18. One of the claims at issue was directed to Aa method for selectively inhibiting

[COX-2] activity in a human host, comprising administering a non-steroidal compound

that selectively inhibits activity of the [COX-2] gene product to a human host in need of

such treatment.@ Id. at 918. We found that the specification lacked written descriptive

support, agreeing with the district court that

it is clear from reading the patent that one critical aspect of the method - a
compound that selectively inhibits [COX-2] activity - was hypothetical, for it
is clear that the inventors had neither possession nor knowledge of such a
compound. . . . [T]he claimed method depends upon finding a compound
that selectively inhibits [COX-2] activity. Without such a compound, it is
impossible to practice the claimed method of treatment.

Id. at 926. We further noted that the specification contained Ano disclosure of any

method for making even a single >non-steroidal compound that selectively inhibits

7
2008-1079
activity of the [COX-2] gene product,’@ and failed to Asteer the skilled practitioner toward

compounds that can be used to carry out the claimed methods.@ Id. at 928, 929.

Alonso attempts to distinguish his claimed invention from Rochester by

emphasizing that he reduced his method to practice and identified the resulting

compound. We are not persuaded by the distinction. A[P]roof of a reduction to practice,

absent an adequate description in the specification of what is reduced to practice, does

not serve to describe or identify the invention for purposes of [the written description

requirement].@ Enzo, 323 F.3d at 969. 6 Moreover, while it is true that Rochester

disclosed no compounds that worked with the claimed method, the one compound

disclosed by Alonso cannot be said to be representative of a densely populated genus.

In Rochester, we reasoned that while the specification

describes what can be done with any compounds that may potentially be
identified through those assays, including formulation into
pharmaceuticals, routes of administration, estimation of effective dosage,
and suitable dosage forms . . . the ’850 patent does not disclose just which
peptides, polynucleotides, and small organic molecules have the desired
characteristics of selectively inhibiting [COX-2]. Without such disclosure
the claimed methods cannot be said to have been described.

Rochester, 358 F.3d at 927 (internal citation and quotation marks omitted). We

additionally found that Rochester had failed to present any evidence that one skilled in

6 The reduction-to-practice argument also implicates § 112’s enablement
requirement. The Board reversed the examiner’s rejection of claim 92 for lack of
enablement. See Decision, slip op. at 12. Alonso argues that the Board’s findings as to
sufficiency of description and enablement are at odds with one another. It is true that
the written description and enablement requirements “usually rise and fall together.
That is, a recitation of how to make and use the invention across the full breadth of the
claim is ordinarily sufficient to demonstrate that the inventor possesses the full scope of
the invention, and vice versa.” LizardTech, 424 F.3d at 1345. However, we have been
clear that “[a]lthough the legal criteria of enablement and written description are related
and are often met by the same disclosure, they serve discrete legal requirements.”
Capon v. Eshhar, 418 F.3d 1349, 1360 (Fed. Cir. 2005). “[A]n invention may be
enabled even though it has not been described.” Rochester, 358 F.3d at 921.
8
2008-1079
the art would have been able to isolate and identify any given compound based on

Rochester’s “vague functional description . . . .@ Id. at 928. Even more recently, we

held that the written disclosure requirement was not met where the claims at issue

covered a broad “genus of recombinant plasmids that contain coding sequences for

DNA polymerase . . . from any bacterial source, [but] the narrow specifications of the

[relevant patents] only disclose[d] the . . . gene coding sequence from one bacterial

source . . . .” Carnegie Mellon Univ. v. Hoffman-LaRoche Inc., 541 F.3d 1115, 1125

(Fed. Cir. 2008) (emphasis added).

The same is true here. The specification of the ’749 Application does not

characterize the antigens to which the monoclonal antibodies must bind; it discloses

only the molecular weight of the one antigen identified in Example 2. This is clearly

insufficient. 7 The specification teaches nothing about the structure, epitope

characterization, binding affinity, specificity, or pharmacological properties common to

the large family of antibodies implicated by the method. While Alonso’s claim is written

as a method, the antibodies themselves are described in purely structural language – “a

monoclonal antibody idiotypic to the neurofibrosarcoma of said human.” This sparse

description of antibody structure in the claim stands in stark contrast to the detailed

method of making the antibodies found in the specification.

The Eli Lilly decision is also instructive. In Eli Lilly, the University of California

laid claim to all vertebrate insulin cDNAs, including the human insulin cDNA, although it

had identified only the cDNA for rat insulin. See Eli Lilly, 119 F.3d at 1567. 8 We ruled

7
It bears mentioning that the examiner encouraged Alonso to amend his
claims to cover only the MAb produced by the identified hybridoma.
8
The claims at issue in Eli Lilly were directed to Aa recombinant plasmid
9
2008-1079
that the written description requirement was not met because Aa description of rat insulin

cDNA is not a description of the broad classes of vertebrate or mammalian insulin

cDNA.@ Id. at 1568. As in Eli Lilly, the specification of the ’749 Application contains

information about only one compound. 9

Apart from the representative number of species test applied by the Board, we

have found adequate written descriptive support for a claimed invention where the

disclosure specifies Arelevant identifying characteristics,@ such as Acomplete or partial

structure, other physical and/or chemical properties, functional characteristics when

coupled with a known or disclosed correlation between function and structure, or some

combination of such characteristics.@ Enzo, 323 F.3d at 964 (emphasis in original).

Alonso argues that there is a well-known correlation between the structure and function

of the neurofibrosarcoma-specific antibodies generated by his disclosed treatment

method. He maintains that the members of the genus of antibodies directed to a

particular patient=s tumor share the same function - they each bind to a patient=s

neurofibrosarcoma, thereby bolstering the patient=s immune mechanism and stimulating

an attack on the tumor cells. As for structure, Alonso argues that because monoclonal

antibodies are secreted from a hybridoma made from a particular neurofibrosarcoma,

replicable in [a] procaryotic host containing within its nucleotide sequence a
subsequence having the structure of the reverse transcript of an mRNA of a vertebrate,
which mRNA encodes insulin.@ Eli Lilly, 119 F.3d at 1563 (emphasis in original).
9
Alonso cites In re Herschler, 591 F.2d 693 (CCPA 1979), where our
predecessor court held that the disclosure of a single corticosteroid was sufficient to
describe the genus of physiologically active steroids that could be used in practicing the
claimed invention. The court based its decision on the fact that the class of implicated
compounds was Achemically quite similar.@ Id. at 701. Alonso argues that the same is
true with respect to the antibodies generated by a patient=s specific neurofibrosarcoma.
However, he points to no evidence in the record corroborating his “similarity” thesis.

10
2008-1079
the antibodies are necessarily specific. He further argues that there is a “well-known

correlation between human antibody structure and antibody function.”

Alonso did not raise this structure-function correlation argument in the

proceedings before the Board. AFailure to advance legal theories before the [B]oard

constitutes a failure to >make a complete presentation of the issues,= and permitting a

party to raise those theories for the first time [after the agency has rendered its final

decision] would be both inefficient and >wasteful of administrative and judicial

resources.=@ Boston Scientific Scimed, Inc. v. Medtronic Vascular, Inc., 497 F.3d 1293,

1298 (Fed. Cir. 2007). Accordingly, we will not consider this newly minted argument on

appeal. 10

III. CONCLUSION

For the aforementioned reasons, the decision of the Board is affirmed.

AFFIRMED.

10 Even were we tempted to consider the argument, Alonso would not be
entitled to relief. In Noelle, the applicant claimed a human monoclonal antibody (or
fragment thereof) secreted from a particular hybridoma that binds to an antigen
expressed on activated T-cells. The application did not, however, disclose any
structural information about the human antigen. Noelle, 355 F.3d at 1345-46. It
described only the mouse antigen. We concluded that the function-structure correlation
test was not met.

If [the applicant] had sufficiently described the human form of CD40CR
antigen, he could have claimed its antibody by simply stating its binding
affinity for the “fully characterized” antigen. [The applicant] did not
describe human CD40CR antigen. Therefore, [the applicant] attempted to
define an unknown by its binding affinity to another unknown.

Noelle, 355 F.3d at 1349. As Alonso has not pointed to any structure for his claimed
antibodies, there is no structure to which he may correlate the function of his claimed
antibodies.
11
2008-1079