Ex Parte Gariepy et al

Board of Patent Appeals and Interferences

Aug 4, 2009

09601644 (B.P.A.I. Aug. 4, 2009)

UNITED STATES PATENT AND TRADEMARK OFFICE
__________

BEFORE THE BOARD OF PATENT APPEALS
AND INTERFERENCES
__________

Ex parte JEAN GARIEPY and MARK ROBERT BRAY
__________

Appeal 2009-0019601
Application 09/601,644
Technology Center 1600
__________

Decided: August 5, 2009
__________

Before FRANCISCO C. PRATS, MELANIE L. MCCOLLUM, and
JEFFREY N. FREDMAN, Administrative Patent Judges.

PRATS, Administrative Patent Judge.

1 University Health network and Molecular Templates Inc. are the real
parties in interest (App. Br. 1).
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DECISION ON APPEAL
This is an appeal under 35 U.S.C. § 134 involving claims to a method
for making a cytotoxic mutant protein or pool of proteins. The Examiner
has rejected the claims as failing to meet the written description and
enablement requirements. We have jurisdiction under 35 U.S.C. § 6(b).
We reverse.
STATEMENT OF THE CASE
Claims 1-7, 9-16, 18, 20, 27-29, 32, 33, 37-41, and 43 stand rejected
and are on appeal (App. Br. 2). Claim 1 is representative of the appealed
subject matter and read as follows:
1. A method for making a cytotoxic mutant protein or pool
of proteins from a cytotoxic wild type protein, said mutant
protein or pool of proteins having receptor-binding specificity
for a receptor that is different from the receptor to which the
wild type protein has receptor binding specificity, comprising:
(A) selecting a heteromeric protein toxin having a toxic
domain or subunit and a binding domain or subunit, wherein the
heteromeric protein toxin is a ribosome inactivating protein;
(B) incorporating mutations into DNA encoding the binding
domain or subunit of the heteromeric protein toxin to produce a
plurality of variant forms of the heteromeric protein toxin;
(C) generating a library of microorganism clones producing
variant forms of the heteromeric protein toxin;
(D) screening the variant forms of the heteromeric protein
toxin of said library against a population of screening cells by
(i) isolating clones or pools of clones producing said variant
forms of the heteromeric protein toxin, (ii) treating preparations
of said population of screening cells with variant forms of the
heteromeric protein toxin produced by the isolated clones or
pools of clones, (iii) observing the treated preparations of said
population of screening cells for toxicity, and (iv) selecting
based on the observation of toxicity a cytotoxic mutant protein
or pool of cytotoxic mutant proteins that inhibits or kills said
population of screening cells to a greater extent than the wild-
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type cytotoxic protein, whereby said selected mutant protein or
pool of proteins has the different receptor binding specificity
that is reflected by the observation of toxicity, wherein the
screening cells are insensitive to the selected cytotoxic
heteromeric protein toxin at a concentration used in the
screening; and
(E) making additional copies of the selected cytotoxic mutant
protein or pool of proteins.

The Examiner cites the following documents as evidence of
unpatentability:
Smith US 6,833,131 B1 Dec. 21, 2004
Sheppard US 2002/0161203 A1 Oct. 31, 2002
D’Andrea US 2003/0188326 A1 Oct. 2, 2003

M.R. Hartley et al., Cytotoxic ribosome-inactivating lectins from
plants, 1701 BIOCHIMICA ET BIOPHYSICA ACTA 1-14 (2004).

Lynne M. Roberts et al., Ribosome-Inactivating Proteins: Entry into
Mammalian Cells and Intracellular Routing, 4 MINI REVIEWS IN MEDICINAL
CHEMISTRY 505-512 (2004).

Maria Giulia Battelli, Cytotoxicity and Toxicity to Animals and
Humans of Ribosome- Inactivating Proteins, 4 MINI REVIEWS IN MEDICINAL
CHEMISTRY 513-521 (2004).

Yasufumi Kaneda, Gene Therapy: A Battle Against Biological
Barriers, 1 CURRENT MOLECULAR MEDICINE 493-499 (2001).

Examination Guidelines on Written Description (uspto.gov/web/
menu/written.pdf).

The following rejections are before us for review:
Claims 1-7, 9-16, 18, 20, 27-29, 32, 33, 37-41 and 43 stand rejected
under 35 U.S.C. § 112, first paragraph, as failing to comply with the written
description requirement (Ans. 3-14).
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Claims 1-7, 9-16, 18, 20, 27-29, 32, 33, 37-41 and 43 stand rejected
under 35 U.S.C. § 112, first paragraph, “because the specification, while
being enabling for methods of for making a cytotoxic mutant protein or pool
of Shiga toxin or Shiga-like toxin proteins, does not reasonably provide
enablement for making mutants for any heteromeric ribosome inactivating
protein with a different receptor binding specificity” (Ans. 14).

WRITTEN DESCRIPTION
ISSUE
The Examiner finds that the genus of cytotoxic proteins recited in the
claims is “broad and includes species named in the specification and
claimed, such as Shiga toxin, Shiga-like toxins, ricin, abrin, gelonin, crotin,
pokeweed antiviral protein, saporin, momordin, modeccin, sarcin, diphtheria
toxin and Psudomonas [sic] aeruginosa exotonin A, as well as other species
not described, such as snake, lizard, spider and insect venoms” (Ans. 4
(citing Smith and Sheppard)). In contrast, the Examiner finds, the
Specification “provides specific embodiments, working or otherwise, only
for Shiga-toxin and Shiga-like toxins” (id.).
The Examiner further finds that, in using screening cells insensitive to
the Shiga and Shiga-like toxins, Appellants’ Example 4 used a specific cell
line, CAMA-I, because it lacked the CD77 receptor for those toxins (id.). In
contrast, the Examiner argues, the Specification “does not disclose cell lines
that similarly lack the receptors for the other heteromeric protein toxins that
constitute the genus” of toxin-insensitive cells recited in claim 1 (id.).
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Based on these findings, the Examiner contends that the Specification
“does not provide a representative number of species to show possession
over the entire genus claimed” (id. at 5).
The Examiner notes that “the examined claims do not require that the
screening cell line lack the receptor recognized by the wild-type toxin” (id.).
The Examiner further notes that, even with respect to the exemplified Shiga
toxin, the Specification does not identify the receptor that the toxin bound,
and therefore, “the practitioner would not be reasonably apprised the
Appellant[s were] in possession of the claimed invention, in regard to the
particular species of Shiga toxin or Shiga-like toxin” (id. at 5-6).
Appellants contend that the claims require the use of ribosome
inactivating proteins, or RIP proteins, which “represent a class of known and
characterized proteins,” as evidenced by publications submitted with the
Appeal Brief (App. Br. 5, 19 (Evidence Appendix)). Moreover, Appellants
argue, the “invention here is a method, not the proteins per se” (id.). Thus,
the claimed invention takes advantage of the binding properties of RIPs “to
provide a method for making proteins that bind to different receptors, but
this use requires no knowledge of the starting sequence” of the proteins (id.).
With respect to obtaining cell lines useful in the screening process,
Appellants urge that “[t]hese cells already exist. All that is required is
pairing a cell of interest with an appropriate RIP that does not bind to the
surface of that cell as reflected by insensitivity to the toxin” (id. at 6). Thus,
Appellants urge, [i]n the unlikely event that some cell should possess every
surface marker to which an RIP binds, then use of that cell would not fall
within the scope of the claims since these cells could not be ‘insensitive to
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the selected cytotoxic heteromeric protein toxin at a concentration used in
the screening’ as required in the claims” (id. at 6-7).
In view of the positions advanced by Appellants and the Examiner,
the issue with respect to this rejection is whether the Examiner erred in
finding that claims involving screening methods, which test the toxicity of
mutated forms of the known class of RIP proteins against cells lacking
sensitivity to the proteins’ wild-type forms, lack descriptive support because
the examples in the Specification are limited to testing the toxicity of
mutated forms of Shiga toxin, and because the Specification describes only a
single cell line lacking sensitivity to the wild-type form of the Shiga toxin.

FINDINGS OF FACT (“FF”)
1. Claim 1 recites a method for making a cytotoxic mutant protein, or
pool of proteins, from a cytotoxic wild type protein. The mutant proteins
must have binding specificity for a receptor that is different from the
receptor to which the wild-type protein specifically binds.
2. Claim 1 includes the steps of:
(A) selecting a heteromeric ribosome inactivating protein toxin that
has a toxic domain/subunit and a binding domain/subunit;
(B) incorporating mutations into the DNA encoding the binding
domain/subunit of the toxin to produce a plurality of variant forms of the
toxin;
(C) generating a library of microorganism clones that produce the
variant forms of the toxin;
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(D) screening the variant forms of the toxin from the library against
a population of screening cells to determine which of the mutated toxins is
toxic to the cells; and
(E) making additional copies of the cytotoxic mutant protein or
pool of proteins obtained in step (D).
3. Claim 1 requires the screening process of step (D) to be performed
by:
(i) isolating the clones or pools of clones that produce the variant
forms of the toxin,
(ii) treating preparations of the screening cells with variant forms of
the heteromeric protein toxin produced by clones,
(iii) observing the treated preparations of the screening cell population
for toxicity, and
(iv) selecting, based on the observation of toxicity, a cytotoxic mutant
protein or pool of cytotoxic mutant proteins that inhibits or kills the
population of screening cells to a greater extent than the wild-type cytotoxic
protein.
4. Claim 1 also requires the screening cells to be insensitive to the wild-
type form of the selected toxin at a toxin concentration used in the screening.
5. The Specification discloses that the method recited in claim 1 allows a
practitioner to “screen[] combinatorial protein libraries of the toxin’s
template to find mutant toxins that kill specific cells or cell types” (Spec. 2).
6. Claim 1 limits the screening process to one that evaluates mutant
heteromeric ribosome inactivating proteins.
7. The Specification discloses that the family of heteromeric plant and
bacterial toxins “includes examples such as Shiga and Shiga-like toxins, the
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E. coli heat-labile enterotoxins, cholera toxin, diphtheria toxin, pertussis
toxin, Pseudomonas aeruginosa exotoxin A as well as plant toxins such as
ricin and abrin” (Spec. 6 (citations omitted)).
8. According to the Specification, “[b]ased on their ability to block
protein synthesis, proteins such as Shiga and Shiga-like toxins as well as
ricin, abrin, gelonin, crotin, pokeweed antiviral protein, saporin, momordin,
modeccin, sarcin, diphtheria toxin and exotoxin A have been referred to as
ribosome-inactivating proteins (RIP) (id.).
9. Appellants cite a number of publications to support the assertion that
RIPs are a class of known and characterized proteins (App. Br. 19 et seq.
(Evidence Appendix)).
10. While the Examiner cites Smith and Sheppard as evidence that the
claims encompass a number of toxins not mentioned in the Specification
(Ans. 4), the Examiner does not dispute the fact that RIPs are a class of
known and characterized proteins.
11. Claim 1 does not limit the screening cells to any particular cell type or
cell line.
12. The Specification states that “[t]he target cell may be a tumour cell,
for example, a breast cancer cell” (Spec. 3).
13. The Specification discloses examples in which Shiga toxin mutants
are tested against two breast cancer cell lines, SK-BR-3 and CAMA-I (id. at
17-23). Of the two cell lines, only the CAMA-I line meets the requirement
in claim 1, that the screening cells be insensitive to the wild-type toxin, in
this case Shiga toxin (id. at 22). Three Shiga toxin mutants were shown to
have greater cytotoxicity to CAMA-I than wild-type Shiga toxin (id.; see
also Figure 6).
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14. The Specification does not provide working examples in which any
other RIPs are tested against any other cell lines.
15. The Examiner cites Roberts as evidence that the RIP ricin can bind to
a number of different cell surface glycoproteins, and that therefore “[t]he
practitioner would not envision that the Appellant had process [sic,
possession] of mutant proteins that have different receptor specificity” (Ans.
8).
16. The Examiner cites Battelli as evidence that the interaction between
cells and RIPs was more complicated than could be predicted based on
structure, and that, accordingly, “it is clear that the genus of RIPs is
heterogeneous, unpredictable, and complicated in the mechanism of action.
Therefore, one of skill in the art would not envision that the Appellant had
possession of the invention as now claimed” (Ans. 9).
17. Apparently noting that certain claims encompassed using the claimed
screening method to prepare gene therapy vectors, the Examiner cites
Kaneda as evidence that gene therapy is not without its problems, and “that
various gene delivery systems, including adenovirus systems, have well
known limitations that have prevented safe and successful methods of gene
therapy” (id. at 10). Kaneda also discloses, however, that gene therapy has
proven successful in certain circumstances (Kaneda 493).
18. The Examiner cites D’Andrea as evidence that a skilled artisan
“would appreciate that insensitivity to a toxin might result from a variety of
reasons, such as amplification of the gene of a target protein or an enhanced
toxin efflux mechanism in the insensitive cell” and that therefore, “[w]ithout
recognition of the nature of the receptor to which the mutated protein binds,
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one of skill in the art would not be reasonably apprised that the receptor was
different, as required by the claims” (Ans. 12).

PRINCIPLES OF LAW
The written description requirement “serves 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.” Ariad Pharmaceuticals, Inc. v. Eli Lilly and Co., 560 F.3d 1366,
1371 (Fed. Cir. 2009) (quoting Univ. of Rochester v. G.D. Searle & Co., 358
F.3d 916, 922 (Fed. Cir. 2004)).
To meet the initial burden of establishing a prima facie case of
unpatentability based on a lack of written description, the Examiner must
“present[] evidence or reasons why persons skilled in the art would not
recognize in the disclosure a description of the invention defined by the
claims.” In re Alton, 76 F.3d 1168, 1175 (Fed. Cir. 1996).
While there is some flexibility in how applicants may comply with the
written description requirement, “the patent specification [must] set forth
enough detail to allow a person of ordinary skill in the art to understand
what is claimed and to recognize that the inventor invented what is claimed.”
Rochester, 358 F.3d at 928.
However:
A claim will not be invalidated on section 112 grounds
simply because the embodiments of the specification do not
contain examples explicitly covering the full scope of the claim
language. That is because the patent specification is written for
a person of skill in the art, and such a person comes to the
patent with the knowledge of what has come before. Placed in
that context, it is unnecessary to spell out every detail of the
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invention in the specification; only enough must be included to
convince a person of skill in the art that the inventor possessed
the invention and to enable such a person to make and use the
invention without undue experimentation.

Falkner v. Inglis, 448 F.3d 1357, 1366 (Fed. Cir. 2006) (quoting
LizardTech, Inc. v. Earth Resource Mapping, PTY, Inc., 424 F.3d 1336,
1345 (Fed.Cir.2005)); see also Capon v. Eshhar, 418 F.3d 1349, 1359 (Fed.
Cir. 2005) (“It is not necessary that every permutation within a generally
operable invention be effective in order for an inventor to obtain a generic
claim, provided that the effect is sufficiently demonstrated to characterize a
generic invention.”).
In addition to relying on the knowledge of a skilled artisan, whether a
disclosure provides adequate descriptive support “depends upon the context
of the claimed invention.” Ariad, 560 F.3d at 1372. Thus, for example, in
Ariad our reviewing court found that claims broadly directed to methods of
reducing NF-KB-mediated effects in cells lacked descriptive support where
the specification hypothesized that three types of molecules would be able to
accomplish the claimed function, but rather than providing actual working
examples, simply made “mere mention of a desired outcome.” Id. at 1375;
see also Rochester, 358 F.3d at 927-28 (claims reciting use of compound
capable of selectively inhibiting prostaglandin H synthase-2 held to lack
written description where specification disclosed screening method, but no
compounds having the claimed activity).
In contrast, in Falkner v. Inglis, the court affirmed this Board’s
finding that claims to a modified pox virus vaccine had descriptive support,
despite the fact that the specification focused on viruses other than pox virus,
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provided no examples directed to pox virus, and discussed pox virus only in
general terms relating to the inventive disclosure. See Falkner, 448 F.3d at
1364-67. Given extrinsic evidence that the critical portions of a pox virus in
relation to the disclosure were well known, the court reasoned that the
disclosure was sufficient to support the claims. Id.; see also Capon v.
Eshhar, 418 F.3d at 1354-58 (court vacated Board’s finding of lack of
descriptive support for claims directed to combinations of known genes
where specifications failed to provide explicit sequence disclosures, but
where genes’ sequences were known in the art); also Noelle v. Lederman,
355 F.3d 1343, 1349 (Fed. Cir. 2004) (“[A]s long as an applicant has
disclosed a fully characterized antigen, either by its structure, formula,
chemical name, or physical properties, or by depositing the protein in a
public depository, the applicant can then claim an antibody by its binding
affinity to that described antigen.” (internal quotations omitted)).
Ultimately, therefore, the test for determining whether a specification
is sufficient to support a particular claim “is whether the disclosure of the
application relied upon ‘reasonably conveys to the artisan that the inventor
had possession at that time of the later claimed subject matter.’” Ralston
Purina Co. v. Far-Mar-Co, Inc., 772 F.2d 1570, 1575 (Fed. Cir. 1985)
(quoting In re Kaslow, 707 F.2d 1366, 1375 (Fed. Cir. 1983)).

ANALYSIS
We agree with Appellants that the Examiner erred in finding that the
claims lack descriptive support. In contrast to claims requiring a specific
therapeutic compound unknown in the prior art and undefined in the
Specification, the process of claim 1 is a screening method which, by its
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nature, seeks to identify such compounds. Moreover, the steps in the
process are clearly defined in both the claim and Specification.
Although not recited as the first step, it is evident that to practice the
invention one must initially select a cell type or cell line of interest that is
amenable to the screening method (see FF 2, 3). As noted above, the
Specification states that tumor cells, including breast cancer cells, are of
particular interest (FF 12). Given the general thrust in the Specification that
the method is for identifying chemotherapeutic agents for killing undesirable
cells (see FF 5), a skilled artisan would thus have reasoned that the process
would be useful for screening other known cancer cells or tumor cells.
Simply put, if the practitioner seeks to find agents capable of killing lung
cancer cells, then the practitioner would use a primary or immortalized lung
cancer cell line of interest as the screening cells.
To practice the method recited in claim 1, the practitioner also must
determine whether the cells of interest lack sensitivity to the wild-type form
of a heteromeric ribosome inactivating protein toxin, or RIP (see FF 4). The
Examiner takes issue with the fact that the Specification exemplifies only a
single cell line that lacks sensitivity to a single RIP (Ans. 4).
However, the record contains significant evidence, and the Examiner
does not dispute, that RIPs are a recognized and characterized class of
proteins (FF 7-10). Thus, in the instant case, if the practitioner seeks to find
agents capable of killing lung cancer cells, then the practitioner screens the
cell line of interest against RIPs, an art-recognized class of proteins, to
determine if the cell he or she wants to kill is insensitive to any of them. As
Appellants point out, if a particular cell line is sensitive to every RIP tested,
then that cell line is not amenable to the claimed invention.
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In the process of claim 1, once the practitioner obtains an RIP to
which the target cells are insensitive, a library of variant forms of that RIP is
generated by creating mutations in the receptor binding subunit (FF 2), and
the cells are screened to determine which, if any, of the variant forms of the
RIP are cytotoxic to the cells of interest (FF 2, 3). The cytotoxic forms of
the RIP are then selected and additional copies made (id.).
The Examiner urges that, given the complexity and unpredictability in
the RIP-receptor binding association, Appellants’ Specification fails to
demonstrate generic possession of RIP variants that have different receptor
specificity than their wild-type counterparts, as required by the claim 1 (see
FF 15-18). We are not persuaded that the Specification fails to adequately
support the claims.
As noted above, claim 1 is directed to a screening process, which is
investigatory by nature, and also lacks predictability by its nature. Thus,
rather than using solely functional language to generically recite a
therapeutic compound whose structure has not been described in the
Specification, see, e.g., Rochester, 358 F.3d at 927-28, claim 1 recites a
specific series of enumerated steps using art-recognized materials to identify
proteins having specifically defined properties. The Specification discloses
that the screening process in fact identified three mutant proteins having the
desired properties (FF 13).
In sum, because the Specification clearly sets out the steps required to
practice the method recited in claim 1, and because a skilled artisan would
understand what materials would be useful in the process, we reverse the
Examiner’s rejection of claim 1 as lacking written description.
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Claim 18 depends from claim 1, and recites “[a] method for
identifying therapeutic proteins having binding specificity for a target cell.”
Claim 18 requires performing the process of claim 1, and the additional steps
of screening the obtained cytotoxic mutant RIPs against the target cells and
also against non-target cells and by treating a preparation of target and a
preparation of non-target cells with said cytotoxic mutant protein or pool of
proteins, and “selecting a therapeutic protein or pool of therapeutic proteins
that are effective to inhibit or kill said target cells and that are less effective
at inhibiting or killing said non-target cells than at inhibiting or killing said
target cells.”
Thus, claim 18 adds to claim 1 a step in which the cytotoxic mutant
RIP is tested to see if it is cytotoxic to non-target cells. Because the
Examiner does not point to, and we do not see, any inadequacy in the
Specification’s description of the additional steps recited in this
embodiment, we also reverse the Examiner’s rejection of claim 18 as lacking
written description.
Claim 27 depends from claim 1 and recites “[a] method for
constructing a diagnostic probe for detecting the presence of a cell surface
marker.” Claim 27 requires performing the process of claim 1, and then
“preparing a diagnostic probe by labeling the selected cytotoxic mutant
protein in a manner which maintains the ability of the binding domain or
subunit of the selected cytotoxic mutant protein to specifically bind to the
cell surface marker.”
Thus, claim 27 adds to claim 1 a step in which a detectable label is
attached to the cytotoxic mutant RIP. Because the Examiner does not point
to, and we do not see, any inadequacy in the Specification’s description of
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the additional steps recited in this embodiment, we also reverse the
Examiner’s rejection of claim 27 as lacking written description.
Claim 32 recites “[a] method for making a targeted medicament for
delivery to a target cell having a cell surface marker, said targeted
medicament comprising a binding portion and a medicament portion.”
The Examiner urges that this embodiment encompasses making gene
therapy agents, and that gene therapy is unpredictable (Ans. 10). This fact
does not persuade us that the Specification’s description of this embodiment
is inadequate.
The process is accomplished essentially by performing the steps
recited in claim 1 to obtain a mutant RIP that binds to the cell surface
marker, after which the binding portion of the RIP is sequenced and then
combined with the medicament. As discussed above, we do not agree with
the Examiner that the screening process recited in claim 1 lacks descriptive
support in the Specification. Moreover, because the claim encompasses
combining known medicaments with the mutant RIPs obtained by the
screening method, we do not agree that a person skilled in the art would fail
to recognize that Appellants possessed the claimed synthetic method.
Regarding the issue of preparing gene therapy agents, we note that
Kaneda discloses that certain applications of gene therapy have proved
successful (FF 17). However, a broad claim does not lack written
description merely because it encompasses inoperative embodiments.
Capon, 418 F.3d at 1359 (“It is not necessary that every permutation within
a generally operable invention be effective in order for an inventor to obtain
a generic claim, provided that the effect is sufficiently demonstrated to
characterize a generic invention.”).
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Thus, we agree with Appellants that the Examiner has not made a
prima facie case of lack of written description with respect to claim 32. We
therefore reverse the Examiner’s written description rejection of that claim.
Claim 37 recites a method having the same basic screening steps
recited in claim 1, except that the method is for obtaining nucleic acids that
encode the mutant cytotoxic RIP. Thus, the final step in claim 37 recites
making additional copies of the nucleic acids that encode the cytotoxic
mutant protein, rather than making copies of the protein. Therefore, for
reasons essentially the same as discussed above with respect to claim 1, we
agree with Appellants that the Examiner has not made a prima facie case that
claim 37 lacks descriptive support in the Specification. Accordingly, we
reverse the Examiner’s written description rejection of that claim.
In sum, for the reasons discussed above, we reverse the Examiner’s
rejections of claims 1, 18, 27, 32, and 37, and their dependent claims, as
failing to meet the written description requirement of 35 U.S.C. § 112, first
paragraph.
ENABLEMENT
ISSUE
Claims 1-7, 9-16, 18, 20, 27-29, 32, 33, 37-41 and 43 stand rejected
under 35 U.S.C. § 112, first paragraph, “because the specification, while
being enabling for methods of for making a cytotoxic mutant protein or pool
of Shiga toxin or Shiga-like toxin proteins, does not reasonably provide
enablement for making mutants for any heteromeric ribosome inactivating
protein with a different receptor binding specificity” (Ans. 14).
Applying the oft-cited factors from In re Wands, 858 F.2d 731, 737
(Fed. Cir. 1988), the Examiner finds that the claims broadly encompass
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making mutants of any RIP protein, and that the receptor to which the
mutated RIP binds encompasses “virtually any biological molecule” (Ans.
16). Conversely, the Examiner finds that the Specification only exemplifies
mutating Shiga toxin, and the examples do not establish that the obtained
mutants fail to bind to the Shiga toxin’s receptor (id.).
The Examiner further finds that “the genus of RIPs is heterogeneous,
unpredictable, and complicated in the mechanism of action,” as evidenced
by Battelli (id. at 17). Thus, despite the high skill level of an ordinary
artisan, the Examiner concludes that the amount of experimentation required
to practice the full scope of the claimed invention would be undue (id. at
19).
Appellants contend that the process recited in claim 1 would not
require undue experimentation “since claim 1 itself is essentially the
instructions for performing the method of the invention” (App. Br. 8).
In view of the positions advanced by Appellants and the Examiner,
the issue with respect to this rejection is whether the Examiner erred in
concluding that an ordinary artisan viewing Appellants’ Specification at the
time of filing would have had to experiment unduly to practice the full scope
of the claimed subject matter.

PRINCIPLES OF LAW
The Examiner bears the burden of establishing that practicing the full
scope of the claimed subject matter would have required undue
experimentation. In re Wright, 999 F.2d 1557, 1561-62, 27 USPQ2d 1510,
1513 (Fed. Cir. 1993) (“[T]he PTO bears an initial burden of setting forth a
reasonable explanation as to why it believes that the scope of protection
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provided by that claim is not adequately enabled by the description of the
invention provided in the specification of the application.”).
Enablement is not precluded by the necessity for some
experimentation such as routine screening. However,
experimentation needed to practice the invention must not be
undue experimentation. . . . The test is not merely quantitative,
since a considerable amount of experimentation is permissible,
if it is merely routine, or if the specification in question
provides a reasonable amount of guidance with respect to the
direction in which the experimentation should proceed.

In re Wands, 858 F.2d at 736-37 (citations omitted).
Moreover, “[working] examples are not required to satisfy section
112, first paragraph.” In re Strahilevitz, 668 F.2d 1229, 1232 (CCPA 1982).
For example, in Falkner v. Inglis, the court affirmed this Board’s conclusion
that claims to a modified pox virus vaccine were enabled, despite the fact
that the specification focused on viruses other than pox virus, provided no
examples directed to pox virus, and discussed pox virus only in general
terms relating to the inventive disclosure. Falkner, 448 F.3d at 1365.
Thus, as noted in Amgen, Inc. v. Hoechst Marion Roussel, Inc., 314
F.3d 1313, 1334 (Fed. Cir. 2003):
The enablement requirement is often more indulgent
than the written description requirement. The specification
need not explicitly teach those in the art to make and use the
invention; the requirement is satisfied if, given what they
already know, the specification teaches those in the art enough
that they can make and use the invention without “undue
experimentation.”

ANALYSIS
We agree with Appellants that the Examiner did not make a prima
facie case that practicing the full scope of the claims would have required
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undue experimentation. As discussed above, the claimed processes all
include the screening steps recited in claim 1, or a close variation.
We note, because the outcome is neither clear nor assured, that the
claimed screening methods include an element of unpredictability by their
nature. We also note that a screening method can require significant amounts
of experimentation.
However, a method does not lack enablement merely because its
practice requires a lot of experimentation. See Wands, 858 F.2d at 737
(“The test is not merely quantitative, since a considerable amount of
experimentation is permissible, if it is merely routine, or if the specification
in question provides a reasonable amount of guidance with respect to the
direction in which the experimentation should proceed .”).
In the instant case, as discussed above, the claims are limited to using
RIPs, which are a known and recognized class of proteins (FF 8-10). The
Specification discloses that the screening cells can be tumor cells, with
particular emphasis on breast cancer cells (FF 12). As also discussed above,
an ordinary artisan would understand that some testing would be required to
determine which, if any, RIPs lack cytotoxicity toward the cell line of
interest.
Thus, an ordinary artisan would understand which proteins are to be
mutated and tested, and would also understand and be able to determine
through simple testing methods which types of tumor cells were amenable to
the described screening methods. Given these facts, and the straightforward
nature of the screening steps required in the claimed methods, we do not
agree with the Examiner that undue experimentation would be required to
Appeal 2009-001960
Application 09/601,644

21
practice the full scope of the claims. We therefore also reverse the
Examiner’s enablement rejection.
SUMMARY
We reverse the Examiner’s rejection of claims 1-7, 9-16, 18, 20, 27-
29, 32, 33, 37-41, and 43 stand rejected under 35 U.S.C. § 112, first
paragraph, as failing to comply with the written description requirement.
We also reverse the Examiner’s rejection of claims 1-7, 9-16, 18, 20,
27-29, 32, 33, 37-41, and 43 under 35 U.S.C. § 112, first paragraph, as
failing to enable the full scope of the claimed subject matter.

REVERSED

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