STC.UNM

Patent Trials and Appeals Board

Jul 20, 2020

15395233 - (D) (P.T.A.B. Jul. 20, 2020)

UNITED STATES PATENT AND TRADEMARK OFFICE
UNITED STATES DEPARTMENT OF COMMERCE
United States Patent and Trademark Office
Address: COMMISSIONER FOR PATENTS
P.O. Box 1450
Alexandria, Virginia 22313-1450
www.uspto.gov
APPLICATION NO. FILING DATE FIRST NAMED INVENTOR ATTORNEY DOCKET NO. CONFIRMATION NO.
15/395,233 12/30/2016 Anatoliy Markiv 0310.000067US03 2473
26813 7590 07/20/2020
MUETING, RAASCH & GEBHARDT, P.A.
P.O. BOX 581336
MINNEAPOLIS, MN 55458-1336
EXAMINER
HUYNH, PHUONG N
ART UNIT PAPER NUMBER
1644
NOTIFICATION DATE DELIVERY MODE
07/20/2020 ELECTRONIC
Please find below and/or attached an Office communication concerning this application or proceeding.
The time period for reply, if any, is set in the attached communication.
Notice of the Office communication was sent electronically on above-indicated "Notification Date" to the
following e-mail address(es):
ptodocketing@mrgs.com
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
__________

BEFORE THE PATENT TRIAL AND APPEAL BOARD
__________

Ex parte ANATOLIY MARKIV,
RAVI VENKATA DURVASULA, and ANGRAY SINGH KANG
__________

Appeal 2019-006965
Application 15/395,233
Technology Center 1600
__________

Before ERIC B. GRIMES, FRANCISCO C. PRATS, and
JEFFREY N. FREDMAN, Administrative Patent Judges.

PRATS, Administrative Patent Judge.

DECISION ON APPEAL

Pursuant to 35 U.S.C. § 134(a), Appellant1 appeals from the
Examiner’s decision to reject claims 19, 20, 23–26, and 52. We have
jurisdiction under 35 U.S.C. § 6(b).
We AFFIRM.

STATEMENT OF THE CASE
Appellant’s invention is directed to fusion proteins, and
polynucleotide constructs encoding those proteins, wherein the proteins

1 We use the word “Appellant” to refer to “applicant” as defined in 37
C.F.R. § 1.42. Appellant states that “the real party in interest . . . is the
assignee, STC.UNM.” Appeal Br. 2.
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“include a fluorescent protein domain linked to one or more antibody
domains.” Spec. 10.2
According to the Specification, structural studies of antibodies have
determined that, for optimal antigen binding, “the native distance between
the C-terminus on the variable heavy chain [(VH)] and the N-terminus on the
variable light chain [(VL)] is often approximately 35 Å.” Spec. 10.
The Specification discloses, however, that when preparing a single
polypeptide chain fragment of an antibody’s variable region (scFv), simply
introducing a poly amino acid linker expected to produce optimal spatial
separation between the VH and VL domains can be insufficient to achieve
acceptable antigen binding:
To generate conventional single chain fragment of the variable
region (scFv) antibodies, a 20–30 amino acid linker may be
introduced between these two sites and thus provide a flexible
region of approximately 35 Å. This spacing between the VH
and VL can influence the functionality of the scFv because the
non-covalent interactions between VH/VL interfaces are
involved in antigen recognition. Nevertheless, the VH/VL
pairing exist[s] in equilibrium with the unpaired state, often
resulting in aggregation of the variable chains and, therefore,
reduced antigen recognition and decreased stability relative to
the Fab fragment or whole immunoglobulin.
Spec. 10 (emphasis added).
Appellant’s invention involves preparation of a fusion protein that
contains a fluorescent polypeptide domain flanked by antigen-binding VH
and VL domains of an antibody of interest. See Spec. 10. In particular,
Appellant’s invention involves the finding that, when preparing a fusion
protein that contains VH and VL domains that provide binding to a particular

2 Substitute Specification entered August 17, 2018.
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antigen, the optimal distance (about 35 Å) and appropriate spatial
relationship for functional antigen binding can be achieved by inserting a
certain type of fluorescent polypeptide between the VH and VL domains:
We have engineered a fusion polypeptide that uses a
β-barrel fluorescent domain to bridge the VH and the VL and
enhance stability of the antibody domains by maintaining the
correct spatial geometry between the antibody domains.
Moreover, the fluorescent domain anchors the N-terminus and
the C-terminus on the same plane with similar spatial
dimension to the Fv in the context of a Fab fragment so that
appropriate VH/VL interface interactions may be achieved
resulting in functional binding sites.
Spec. 10.
The exemplified embodiments of Appellant’s inventive fusion
proteins “used monomeric red fluorescent protein (mRFP) derived from
Discosoma to link the VH and VL domain pairing of the recombinant anti-
carbohydrate antibodies B72.3, CA19.9, and 4D5 anti-p185HER2.” Spec.
10.
The Specification uses the term “REDantibody” to refer to the
exemplified mRFP fusion protein constructs. See Spec. 26 (describing
determination of expressed amounts of “REDantibody 4D5,” “REDantibody
CA19.9,” and “REDantibody 72.3”).
The Specification discloses that the B72.3 and CA19.9 antibodies
bind to specific carbohydrate cancer cell surface antigens, which are also
present on the human pathogen T. cruzi, whereas in contrast, the 4D5
antibody binds to a peptide epitope of herceptin:
Functional analysis of the REDantibody was based on
well-characterized properties of B72.3 and CA19.9 antibodies
to recognize sialyl-Tn and sialylated Lewis (Le)a blood group
antigen, respectively, which are part of a panel of markers used
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in cancer diagnostics. The same sialyl-Tn antigen has
previously been detected on the surface of the human pathogen
Trypanosoma cruzi using B72.3 monoclonal antibody.
The CA19.9 also binds to sialyl glycans on the parasite
surface. The 4D5 REDantibody was constructed for use as a
negative control since it recognizes a peptide epitope on
p185HER2, but not sialyl glycan. This was confirmed by the
fluorescent staining of T. cruzi epimastigotes using purified
recombinant anti-glycan REDantibody shown in FIG. 6A and
FIG. 6B. The control REDantibody 4D5 did not label the
parasites (FIG. 6C).
Spec. 27.
Appellant’s claim 19 is representative, and reads as follows:
19. A polynucleotide that encodes the polypeptide
comprising:
a fluorescent domain comprising:
a monomeric fluorescent polypeptide comprising:
a C-terminus; and
an N-terminus;
a first antibody domain covalently linked to the C-
terminus of the fluorescent domain, wherein the first antibody
domain comprises a variable light chain (VL) or a variable
heavy chain (VH); and
a second antibody domain covalently linked to the N-
terminus of the fluorescent domain, wherein the second
antibody domain comprises a variable light chain (VL) or a
variable heavy chain (VH);
wherein the N-terminus of first antibody domain and the
C-terminus of the second antibody domain are separated by a
distance of no less than 30 Å and no more than 40 Å.
Appeal Br., Claims App’x.
The following rejections are before us for review:
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(1) Claims 19, 20, 23–26, and 52, under 35 U.S.C. § 112(a) or 35
U.S.C § 112 (pre-AIA), first paragraph, as failing to comply with the written
description requirement (Final Act. 2–9);3 and
(2) Claims 19, 20, 23–26, and 52, under 35 U.S.C. § 112(a) or 35
U.S.C § 112 (pre-AIA), first paragraph, as lacking enablement for the full
scope of the subject matter claimed (Final Act. 12–18).
WRITTEN DESCRIPTION
The Examiner’s Rejection
The Examiner found that, although Appellant’s claims encompass
polynucleotides encoding fusion constructs including any type of fluorescent
polypeptide, the Specification only describes constructs with the mRFP
fluorescent polypeptide from Discosoma. See Final Act. 5.
The Examiner found that, although Appellant’s claims encompass
polynucleotides encoding fusion constructs having any variable light chain
(VL) and heavy chain (VH) sequences, the Specification does not describe “i)
a complete structure, i.e., polynucleotide encoding a heavy and light chain
variable domains, or ii) partial structure, i.e., polynucleotide encoding the six
CDRs of the genus of first and second antibody domains coupled with
correlation between structure and function, i.e., binding specificity or
affinity of the antibody domain.” Final Act. 5.
Given the Specification’s disclosure of only a small number of
specific examples of fusion constructs encompassed by the rejected claims,
the Examiner reasoned that the Specification does not describe a sufficiently
representative number of species of the claimed genus, such that a skilled

3 Final Action entered November 5, 2018.
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artisan would visualize or recognize the members of the genus. Final Act. 5
(citing Ariad Pharms., Inc. v. Eli Lilly and Co., 598 F.3d 1336, 1350 (Fed.
Cir. 2010)).
The Examiner asserted that it was well known in the art that formation
of an intact antigen binding site requires highly specific coordination of a
number of distinct elements of an antibody, and cited Rudikoff4 and Jubala5
as evidence that the field of antigen-antibody binding, and the manipulation
thereof, was highly unpredictable. Final Act. 6–7.
Based on the small number of examples in the Specification, and the
unpredictability in the art, the Examiner found that Appellant was not in
possession of the full scope of the subject matter encompassed by the claims,
and that Appellant’s claims, therefore, did not satisfy the written description
requirement. Final Act. 7–9.
Analysis
As stated in In re Oetiker, 977 F.2d 1443, 1445 (Fed. Cir. 1992):
[T]he examiner bears the initial burden . . . of presenting a
prima facie case of unpatentability. . . .
After evidence or argument is submitted by the applicant in
response, patentability is determined on the totality of the
record, by a preponderance of evidence with due consideration
to persuasiveness of argument.
We select claim 19 as representative of the claims subject to this
rejection. See 37 C.F.R. § 41.37(c)(1)(iv). Having carefully considered the
evidence and arguments advanced by Appellant and the Examiner,

4 Stuart Rudikoff et al., Single amino acid substitution altering antigen-
binding specificity, 79 PROC. NATL ACAD. SCI. USA 1979–1983 (1982).
5 C.M. Jubala et al., CD20 Expression in Normal Canine B Cells and in
Canine non-Hodgkin Lymphoma, 42 VET. PATHOL. 468−476 (2005).
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Appellant does not persuade us that a preponderance of the evidence fails to
support the Examiner’s finding that claim 19 lacks adequate descriptive
support in Appellant’s Specification.
The written description requirement “ensures that when a patent
claims a genus by its function or result, the specification recites sufficient
materials to accomplish that function - a problem that is particularly acute in
the biological arts.” Ariad v. Lilly, 598 F.3d at 1352–53.
Thus, a “sufficient description of a genus . . . requires the disclosure
of either a representative number of species falling within the scope of the
genus or structural features common to the members of the genus so that one
of skill in the art can ‘visualize or recognize’ the members of the genus.”
Ariad v. Lilly, 598 F.3d at 1350 (quoting Regents of the University of
California v. Eli Lilly & Co., 119 F.3d 1559, 1568-69 (Fed. Cir. 1997)).
Our reviewing court has “set forth a number of factors for evaluating
the adequacy of the disclosure [asserted to support generic claims], including
‘the existing knowledge in the particular field, the extent and content of the
prior art, the maturity of the science or technology, [and] the predictability
of the aspect at issue.’” Ariad v. Lilly, 598 F.3d at 1351 (quoting Capon v.
Eshhar, 418 F.3d 1349, 1359 (Fed. Cir. 2005)) see also 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.”) (emphasis added).
Ultimately, the “test for sufficiency is whether the disclosure of the
application relied upon reasonably conveys to those skilled in the art that the
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inventor had possession of the claimed subject matter as of the filing date.”
Ariad v. Lilly, 598 F.3d at 1351.
In the present case, we agree with the Examiner that Appellant’s
Specification does not disclose a representative number of species sufficient
to convey to a skilled artisan that Appellant possessed the full scope of the
generic subject matter recited in representative claim 19.
Specifically, claim 19 recites a polynucleotide that encodes a
polypeptide. The polypeptide encoded by the claimed polynucleotide has
three portions: a monomeric fluorescent polypeptide flanked by two
antibody domains (a VL chain and a VH chain), which may be linked to either
end of the fluorescent polypeptide. Claim 19 also requires the N-terminus of
the first antibody domain and the C-terminus of the second antibody domain
to be separated by a distance of 30–40 Å.
As noted above, Appellant’s Specification explains that the 30–40 Å
spacing between the first and second antibody domains recited in claim 19 is
crucial to achieving the optimal spatial relationship between the VH and VL
chains that allows efficient antigen binding. See Spec. 10. Thus, when
properly interpreted in light of the Specification, claim 19 recites a genus of
polynucleotides that encodes any fusion protein composed of any type of
fluorescent protein, flanked by any VH and VL chains, wherein the fusion
protein is capable of binding to an antigen of interest.
Because, when interpreted in light of the Specification, claim 19
recites a polynucleotide encoding a fusion protein that necessarily has
antigen binding functionality, Appellant does not persuade us that the
polynucleotide of claim 19 is recited only in structural terms. See Appeal
Br. 7–8; Reply Br. 3–4. Indeed, if a polynucleotide encompassed by claim
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19 encoded a polypeptide that lacked the capacity to bind an antigen, that
polynucleotide would not be useful in accordance with Appellant’s
invention.
As the Examiner found, whereas claim 19 recites a genus of
polynucleotides that encodes any fusion protein composed of any type of
fluorescent protein, flanked by any VH and VL chains, wherein the fusion
protein is capable of binding to an antigen of interest, the Specification
discloses only three examples of polynucleotides capable of antigen binding.
In particular, the only polynucleotides specifically described in the
Specification that are encompassed by claim 19’s genus are the
polynucleotides that encode the REDantibody 4D5, the REDantibody
CA19.9, and the REDantibody B72.3. See Spec. 37–38 (describing insertion
of the mRFP1 gene (encoding the Discosoma red fluorescent protein) in
plasmids encoding antibodies 4D5, CA19.9, and B72.3).
Thus, while the genus of claim 19 encompasses polynucleotides
encoding any type of fluorescent protein flanked by VH and VL chains, the
Specification actually describes only one particular polynucleotide encoding
one specific type of fluorescent protein–the mRFP1 gene encoding the
Discosoma red fluorescent protein–that provides the antigen binding
functionality necessarily required by claim 19. And, the Specification
discloses the use of the Discosoma mRFP in combination with only three
antibodies, two of which bind to related antigens. See Spec. 27 (disclosing
that the B72.3 and CA19.9 antigens are both glycan cancer markers that are
also present on the surface of the human pathogen T. cruzi).
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Appellant contends that the Specification describes a number of
fluorescent proteins that may be used in its fusion constructs, in addition to
the Discosoma RFP. See Appeal Br. 6–7; Reply Br. 7.
We acknowledge the Specification’s assertion that, in addition to the
Discosoma mRFP, about 30 other fluorescent polypeptides can be employed
in the fusion construct of Appellant’s invention. See Spec. 13–14. We
acknowledge the Specification’s assertion that the Discosoma mRFP “can be
readily interchanged with a range of other fluorescent proteins that have
almost identical external tertiary structure, thus opening up the possibility of
creating palettes of stable recombinant monoclonal antibodies with defined
spectral properties for use in, for example, protein arrays, live cell imaging,
and/or immunocytochemical imaging.” Id. at 22 (citation omitted); see also
id. at 34 (“[S]ince the palette of monomeric fluorescent proteins
(mHoneydew to mPlum) are based on the basic architecture of mRFP1 used
in this study, it should be possible to exchange the red fluorophore for these
other colored proteins that have similar 11 β-sheet barrel-like structure.”)
(Citation omitted; emphasis added).
Other than the Discosoma mRFP in REDantibody 4D5, REDantibody
CA19.9, and REDantibody B72.3, however, the Specification does not
describe any specific polynucleotide sequences that encode an antigen-
binding fusion polypeptide, wherein the polypeptide includes one of the
fluorescent proteins asserted in the Specification as being suitable for use in
a fluorescent fusion construct encompassed by representative claim 19.
Thus, while the Specification asserts that a number of different fluorescent
polypeptides can be employed in the antigen-binding constructs encoded by
claim 19’s polynucleotide, the Specification does not describe the specific
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polynucleotide sequences that encode those constructs. The fact that it
might be obvious, based on the disclosures in the Specification, to devise a
polynucleotide sequence encompassed by claim 19, does not demonstrate
that Appellant was in possession of such sequences. See Ariad, 598 F.3d at
1352 (“[A] description that merely renders the invention obvious does not
satisfy the requirement.”).
Indeed, contrary to the assertions elsewhere in the Specification as to
the routineness of substituting other similar proteins for the Discosoma
mRFP, Appellant’s Specification expressly states that, when seeking to
employ fluorescent proteins similar to mRFP, “[o]ur earlier attempts to
construct similar bridged molecules using a related β-barrel structure of
green fluorescent protein (GFP) resulted in molecules that did not bind to the
target antigen.” Spec. 28. We note in particular that, despite Appellant’s
conceded inability to create an antigen-binding fusion construct using GFP,
the Specification lists GFP among the proteins suitable for use in its
constructs. See id. at 13.
As the Examiner points out, moreover, antigen-antibody binding is
highly unpredictable, in that even a small change in the amino acid sequence
of an antibody can significantly affect antigen binding. See Rudikoff 1979
(results of antibody study “suggest that small numbers of substitutions in
antibodies, such as those presumably introduced by somatic mutation, may
in some situations be effective in altering antigen-binding specificity”); id. at
1982 (“We have shown that a single amino acid substitution is capable of
completely altering antigen-binding specificity.”); see also Spec. 33 (“Few
genetically encoded fluorescent antibodies have been reported to date, in
part because it has been proven difficult to maintain native affinity activity
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of antibody domains and maintain native fluorophore activity of the
fluorophore domain.”) (citation omitted).
Thus, to summarize, Appellant’s representative claim 19 recites a
genus of polynucleotides that encode any antigen-binding fusion protein
composed of any type of fluorescent protein, flanked by VH and VL chains
lacking defined sequences. The genus recited in claim 19 therefore
encompasses polynucleotides encoding many different types of fluorescent
proteins. See, e.g., Spec. 13–14. In contrast, Appellant’s Specification only
describes three examples of polynucleotides encompassed by claim 19, all of
which encode only one type of fluorescent protein that provides antigen-
binding functionality (the Discosoma mRFP). And, as the Examiner found,
antigen-antibody binding is highly unpredictable because even small
changes to an antibody construct can eradicate antigen binding, which is
bolstered by the fact that Appellant’s attempts to link VH and VL chains with
the β-barrel green fluorescent protein (GFP) similar to the Discosoma mRFP
did not produce an antigen-binding construct. See Rudikoff 1979, 1982;
Spec. 28.
Given the unpredictability in the art and the lack of examples in the
Specification, the mere fact that individual components encompassed by
claim 19 may have been known separately does not persuade us that the
Specification would have conveyed to skilled artisans that Appellant
possessed the specific combination of elements required by claim 19, having
the antigen-binding functionality required by the claim. See Appeal Br. 8;
Reply Br. 4.
In sum, given that the exemplified species constitute only a small
portion of the subject matter encompassed by the genus recited in
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representative claim 19, and given the high level of unpredictability in the
art, we agree with the Examiner that Appellant’s Specification does not
reasonably convey to skilled artisans that Appellant possessed the full scope
of the subject matter encompassed by claim 19 as of the filing date. We
therefore affirm the Examiner’s rejection of claim 19 for failure to comply
with the written description requirement. Claims 20, 23–26, and 52 fall with
claim 19. See 37 C.F.R. § 41.37(c)(1)(iv).
ENABLEMENT
The Examiner’s Rejection
In rejecting claims 19, 20, 23–26, and 52 as lacking enablement for
the full scope of the subject matter recited in the claims, the Examiner
applied a rationale similar to that discussed above in relation to the written
description rejection. In particular, applying the oft-cited factors of In re
Wands, 858 F.2d 731, 737 (Fed. Cir. 1988), the Examiner determined that, in
contrast to the relatively broad scope of claim 19, Appellant’s Specification
exemplified only three polynucleotides encompassed by the claim, the
polynucleotides encoding the REDantibody 4D5, the REDantibody CA19.9,
and the REDantibody B72.3. See Final Act. 15.
The Examiner again cited Rudikoff and Jubala as evidence that
antigen-antibody binding was highly unpredictable. Final Act. 16–17. The
Examiner also cited Tsien6 and Markiv7 as evidence of unpredictability in
the art of preparing antigen-binding fusion polypeptides containing antibody
domains. Id. at 17.

6 US 7,005,511 B2 (issued Feb. 28, 2006).
7 Anatoliy Markiv et al., Module based antibody engineering: A novel
synthetic REDantibody, 364 J. IMMUNOLOGICAL METHODS 40–49 (2011).
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Based on those findings, the Examiner concluded that “it would
require undue experimentation of one skilled in the art to practice the
invention as claimed.” Final Act. 18.
Analysis
We select claim 19 as representative of the claims subject to this
rejection. See 37 C.F.R. § 41.37(c)(1)(iv). Having carefully considered the
evidence and arguments advanced by Appellant and the Examiner,
Appellant does not persuade us the Examiner erred in concluding that
Appellant’s Specification fails to enable the full scope of the subject matter
recited in claim 19.
“[T]o be enabling, the specification of a patent must teach those
skilled in the art how to make and use the full scope of the claimed invention
without undue experimentation.” Trustees of Boston University v. Everlight
Electronics Co., Ltd., 896 F.3d 1357, 1362 (Fed. Cir. 2018) (bracketing in
original; internal quotations omitted); In re Vaeck, 947 F.2d 488, 496 (Fed.
Cir. 1991) (“[T]here must be sufficient disclosure, either through illustrative
examples or terminology, to teach those of ordinary skill [in the art] how to
make and how to use the invention as broadly as it is claimed.”).
In the present case, as discussed above in relation to the rejection for
lack of written description, claim 19 recites a genus of polynucleotides that
encodes any fusion protein composed of any type of fluorescent protein,
flanked by any VH and VL chains, wherein the fusion protein is capable of
binding to an antigen. As discussed above, however, the Specification
discloses only three examples of polynucleotides capable of antigen binding,
the polynucleotides that encode the REDantibody 4D5, the REDantibody
CA19.9, and the REDantibody B72.3. See Spec. 37–38.
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As also discussed above, antigen-antibody binding is highly
unpredictable because even small changes to an antibody construct can
eradicate antigen binding, which is bolstered by the fact that Appellant’s
own attempts to link VH and VL chains with the β-barrel green fluorescent
protein (GFP) similar to the Discosoma mRFP did not produce an antigen-
binding construct. See Rudikoff 1979, 1982; Spec. 28.
As the Examiner points out, moreover, Tsien discloses that the native
form of the fluorescent protein employed in the Specification’s exemplified
embodiments “RFP has a propensity to form tetrameric structures” (Tsien
7:5-6), a problem that can require significant modifications to address (see
id. at 7:14-21).
As the Examiner also points out, in a teaching very similar to the
disclosure at page 28 of Appellant’s Specification,8 Markiv teaches that
attempts to link VH and VL chains with the β-barrel green fluorescent protein
(GFP) similar to the Discosoma mRFP did not produce an antigen-binding
construct:
Our earlier attempts to construct similar bridged molecules
using a related β-barrel structure of green fluorescent protein
EGFP (PDB 1GFL) resulted in molecules that did not bind to
the target antigen. We speculate that since the EGFP could
exist as a dimer at higher protein concentrations its assembly
could sterically hinder VH/VL domain pairing, with or without
the introduction of Gly4Ser linkers (data not shown). This
obstacle was overcome by using a monomeric fluorescent
protein with a β-barrel structure exemplified by mRFP1.
Markiv 46 (citations omitted).

8 Three of the four authors of Markiv are the three co-inventors of the
present application, and Markiv includes a number of the same disclosures
as in the present Specification.
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Accordingly, given that the Specification’s exemplified species
constitute only a small portion of the subject matter encompassed by
representative claim 19, and given the high level of unpredictability in the
art, particularly the fact that Appellant’s own attempts to link VH and VL
chains with the β-barrel green fluorescent protein (GFP) similar to the
Discosoma mRFP did not produce an antigen-binding construct (Spec. 28),
we agree with the Examiner that a skilled artisan would have required undue
experimentation to practice the full scope of the subject matter encompassed
by claim 19.
We acknowledge, as Appellant contends, that the lack of antigen
binding when using the β-barrel GFP as the fluorescent protein in the
antibody constructs was addressed by using the similar Discosoma mRFP.
See Appeal Br. 10; see also Spec. 29; Markiv 46. As noted above, however,
the Examiner has conceded that polynucleotides that encode the mRFP as
fluorescent polypeptide, the REDantibody 4D5, the REDantibody CA19.9,
and the REDantibody B72.3, are enabled. Representative claim 19,
moreover, encompasses numerous types of proteins other than the
Discosoma mRFP as the fluorescent polypeptide (see Spec. 13–14), none of
which has been shown to provide antigen binding when combined with VH
and VL chains, and at least one of which (GFP) is described on page 28 of
the Specification as not providing a construct that binds to antigen.
Thus, on the current record, although the Specification lists a number
of alternative fluorescent proteins (see Spec. 13–14), the sole attempt by
Appellant to use a fluorescent protein other than the Discosoma mRFP met
with failure, despite the fact that the attempt was made using a protein (GFP)
with a β-barrel structure similar to the Discosoma mRFP. Accordingly,
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given the undisputedly high level of unpredictability in the art, combined
with Appellant’s own lack of success in preparing antigen-binding
constructs using fluorescent proteins other than the Discosoma mRFP
(despite using a fluorescent protein similar to the mRFP), Appellant does not
persuade us that the Examiner erred in finding that undue experimentation
would be required to practice the full scope of the claimed invention.
Appellant contends that its working examples “show that fluorescent
fusion polypeptides can be designed and constructed to specifically bind to
targets from widely divergent species (Trypanosoma cruzi and human),
establishing that success is not dependent upon careful selection of
antibodies that detect an analyte derived from a particular species.” Appeal
Br. 11. We are not persuaded.
According to the Specification, the T. cruzi antigens that bound to the
REDantibody B72.3 and REDantibody CA19.19 are the same antigens as
those on the surface of human cancer cells. See Spec. 27 (“The same sialyl-
Tn antigen has previously been detected on the surface of the human
pathogen Trypanosoma cruzi using B72.3 monoclonal antibody. The
CA19.9 also binds to sialyl glycans on the parasite surface.”). The
Examiner, moreover, has conceded that polynucleotides encoding those
fusion constructs are enabled.
Appellant contends that its Figures 16B–E describe polynucleotide
constructs that include fluorescent proteins other than the Discosoma mRFP.
Appeal Br. 12. Appellant contends that it has “has produced the fluorescent
fusion polypeptides expressed by these constructs, providing conclusive
evidence that the description provided in Appellant’s specification does,
indeed, enable those of ordinary skill in the art to produce fluorescent fusion
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polypeptides using alternative fluorescent polypeptide domains.” Id. at 12–
13.
We are not persuaded. Other than the brief description of the plasmid
maps shown in Figures 16B–E (see Spec. 9), we do not discern, nor does
Appellant identify, any specific discussion in the Specification about the
polynucleotide constructs shown in those figures. Nor does Appellant
identify any specific discussion in the Specification that describes expression
of the constructs encoded by the polynucleotides in Figures 16B–E.
Appellant, moreover, points to no evidence of record to support the assertion
in its brief that it has expressed the polypeptides encoded by the
polynucleotides in Figures 16B–E. Further, even if they were expressed,
Appellant does not identify on this record any specific evidence suggesting
that the polypeptides encoded by the polynucleotides of Figures 16B–E,
actually bind to an antigen.
In sum, for the reasons discussed, Appellant does not persuade us that
the Examiner erred in concluding that Appellant’s Specification fails to
enable the full scope of the subject matter recited in claim 19. We therefore
affirm the Examiner’s rejection of claim 19 for failure to comply with the
enablement requirement. Claims 20, 23–26, and 52 fall with claim 19. See
37 C.F.R. § 41.37(c)(1)(iv).
Appeal 2019-006965
Application 15/395,233

19
CONCLUSION
In summary:
Claims
Rejected
35 U.S.C. § Reference(s)/
Basis
Affirmed Reversed
19, 20, 23–
26, 52
112, first
paragraph
Lack of
Written
Description
19, 20,
23–26, 52

19, 20, 23–
26, 52
112, first
paragraph
Lack of
Enablement
19, 20,
23–26, 52

Overall
Outcome
19, 20,
23–26, 52

TIME PERIOD FOR RESPONSE
No time period for taking any subsequent action in connection with
this appeal may be extended under 37 C.F.R. § 1.136(a). See 37 C.F.R.
§ 1.136(a)(1)(iv).

AFFIRMED