Ex Parte Reed

Patent Trial and Appeal Board

Nov 26, 2013

11834897 (P.T.A.B. Nov. 26, 2013)

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.
11/834,897 08/07/2007 Thomas D. Reed 2584.0280001/RWE/GER 1472
80011 7590 11/27/2013
Sterne, Kessler, Goldstein & Fox P.L.L.C.
1100 New York Avene
N.W.
Washington, DC 20005
EXAMINER
LEAVITT, MARIA GOMEZ
ART UNIT PAPER NUMBER
1633
MAIL DATE DELIVERY MODE
11/27/2013 PAPER
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.
PTOL-90A (Rev. 04/07)

UNITED STATES PATENT AND TRADEMARK OFFICE
____________

BEFORE THE PATENT TRIAL AND APPEAL BOARD
____________

Ex parte THOMAS D. REED
____________

Appeal 2012-0055191
Application 11/834,897
Technology Center 1600
____________

Before DONALD E. ADAMS, ANNETTE R. REIMERS, and SUSAN L. C.
MITCHELL, Administrative Patent Judges.

ADAMS, Administrative Patent Judge.

DECISION ON APPEAL2
This appeal under 35 U.S.C. § 134 involves claims 166-170 and 174-
176 (App. Br. 7).3 Examiner entered rejections under the written description
and enablement provisions of 35 U.S.C. § 112, first paragraph. We have
jurisdiction under 35 U.S.C. § 6(b).
We affirm.

1 This Appeal is related to Appeal No. 2012-005520, Application No.
11/836,563 (see App. Br. 5).
2 The Real Party in Interest is Intrexon Corporation (App. Br. 4).
3 Pending claims 171-173 stand “withdrawn from consideration” (App. Br.
7). Examiner found the subject matter of claim 177 allowable if rewritten in
independent form (Ans. 5).
Appeal 2012-005519
Application 11/834,897

2
STATEMENT OF THE CASE
The claims are directed to an isolated polynucleotide. Claims 166 and
176 are representative and are reproduced in the Claims Appendix of
Appellant’s Brief.
Claims 166-170 and 174-176 stand rejected under the written
description and enablement provisions of 35 U.S.C. § 112, first paragraph.
ISSUES
Does the preponderance of evidence on this record support
Examiner’s:
1. finding that Appellant’s Specification fails to provide written
descriptive support for the full scope of Appellant’s claimed invention; and
2. conclusion that undue experimentation would be required to
practice the full scope of claimed invention?
FACTUAL FINDINGS (FF)
FF 1. “Protein Kinase A or PKA … can phosphorylate serine and
threonine residues” (Spec. 1: ¶ [0004]).
FF 2. During the November 14, 2013 Oral Hearing, Appellant’s
representative explained that: (1) “protein kinase A,” as that term is used in
Appellant’s claimed invention, represents a genus of isoforms and (2) the
polypeptide encoded by the polynucleotide of Appellant’s claimed invention
may inhibit one or more of the protein kinase A isoforms (see Ans. 13
(“There are two classes of PKA, types I and II, which contain … regulatory
subunits…. Multiple isoforms of the regulatory subunits … and catalytic
subunits … are expressed and may contribute to the specificity of PKA”)).
Appeal 2012-005519
Application 11/834,897

3
FF 3. Appellant’s “invention intends to capture all combinations of
homopolyligands and heteropolyligands without limitation to the examples”
provided in Appellant’s Specification (id. at 4: ¶ [0010]; see also id. at 7:
¶ [0032] (“The instant invention is directed to all possible combinations of
homopolyligands and heteropolyligands without limitation”); see also id. at
13: ¶ [0051]).
FF 4. Appellant discloses that “ligands of the invention are optionally
linked to additional molecules or amino acids that provide an epitope tag, a
reporter, and/or a cellular localization signal,” wherein each may represent
the same or “different molecules” (id. at 4-5: ¶ [0015]; see also id. at 13:
[0052]).
FF 5. Appellant discloses that “[p]olyligands may comprise any two or
more of SEQ ID NOS: 55-216, wherein Xaa is any amino acid” (id. at
7: ¶ [0032]).
FF 6. Appellant discloses that “SEQ ID NOS: 55-132 are subsequences of
SEQ ID NOS: 12-54, where … the locations of the PKA phosphorylatable
residues are represented by Xaa,” wherein “Xaa can be any amino acid,”
including naturally and non-naturally occurring amino acids (id. at ¶ [0033]).
FF 7. Appellant discloses that “[t]here are numerous ways to combine SEQ
ID NOS: 55-216 into homopolymeric or heteropolymeric ligands” (id. at
¶ [0032]).
FF 8. Appellant discloses that “[t]he length and composition of the spacer
may vary” (id. at 13: ¶ [0051]).
Appeal 2012-005519
Application 11/834,897

4
FF 9. Appellant exemplifies the structure of three heteropolyligands,
wherein:
[T]he PKA polyligand of SEQ ID NO: 1 is encoded by
SEQ ID NO:2, SEQ ID NO:3 and by SEQ ID NO:4, wherein
the codons of SEQ ID NO:3 and SEQ ID NO:4 have been
optimized for vector insertion. SEQ ID NO:4 includes flanking
restriction sites. . . . SEQ ID NO: 1 is an embodiment of a
polyligand of the structure A-S1-B-S2-C-S3-D, wherein A is
SEQ ID NO:142, B is SEQ ID NO:143, C is SEQ ID NO:144,
and D is SEQ ID NO:145, and wherein S1 is a spacer of the
amino acid sequence PGAGA, S2 is a spacer of amino acid
sequence GGGG, and S3 is a spacer of amino acid sequence
AAGGAA. A polyligand of structure A-S1-B-S2-C-S3-D is
also called herein a heteropolyligand.
SEQ ID NO:5 is an embodiment of a polyligand of the
structure X-S4-Y-S5-Z, wherein X is SEQ ID NO:153, Y is
SEQ ID NO:154, and Z is SEQ ID NO:155, and wherein S4 is a
spacer of amino acid sequence GAGA, and S5 is a spacer of
amino acid sequence AGAG. The PKA polyligand of SEQ ID
NO:5 is encoded by SEQ ID NO:6 and by SEQ ID NO:7,
wherein the . . . codons of SEQ ID NOS:6 and 7 have been
optimized for vector insertion. SEQ ID NO:7 includes flanking
restriction sites. A polyligand of structure X-S4-Y-S5-Z is also
called herein a heteropolyligand.
SEQ ID NO:8 is an embodiment of a polyligand of the
structure X-S6-Y-S7-Z-S8-A-S9-B, wherein X is SEQ ID
NO:146, Y is SEQ ID NO:147, Z is SEQ ID NO:148, A is SEQ
ID NO:149, and B is SEQ ID NO:150, and wherein S6 is a four
amino acid spacer with the sequence PGAG, S7 is an eight
amino acid spacer with the sequence PAAAGGGP, S8 is a
seven amino acid spacer with sequence PAGAGAG, and S9 is a
five amino acid spacer with the sequence AAAAP. The PKA
polyligand of SEQ ID NO:8 is encoded by SEQ ID NO:9, SEQ
ID NO:10, and by SEQ ID NO:11, wherein the . . . codons of
SEQ ID NOS:10 and 11 have been optimized for vector
insertion. SEQ ID NO:11 includes flanking restriction sites. A
Appeal 2012-005519
Application 11/834,897

5
polyligand of structure X-S6-Y-S7-Z-S8-A-S9-B is also called
herein a heteropolyligand.

(Id. at 22-23: ¶¶ [0088]-[0090].)
FF 10. Examiner finds that Appellant’s Specification fails to provide written
descriptive support for, or provide an enabling description of,
[A] genus of isolated nucleic acid sequences encoding a PKA
polyligand comprising a structure selected from the group
consisting of X-S-X and X-S-Y, wherein X and Y are different
polypeptide monomers, wherein X and Y are monomers
selected from an amino acid sequence having at least 85%
(claim 166), 90% (claim 174), 95% (claim 175)[,] and 98%
(claim 176) sequence identity to any of the polypeptides of
SEQ ID NOS: 55-201 . . . , able to inhibit PKA activity.
(Ans. 7.)
FF 11. Examiner finds that Appellant fails to disclose a “core structure” that
is representative of the “full scope of the claimed genera” (id. at 12-13; see
also id. at 11 (Examiner finds “no evidence of record that the
polypeptides/ligands of SEQ ID NOS: 55-216 share a common structural
motif or a common active site mechanism to define the genus of PKA
substrates other than being substrates of PKA”)).
FF 12. Examiner finds that
While one of skill in the art can readily envision numerable
species of nucleic acid sequences that are at least a given %
identity to a reference nucleotide sequence and . . . encode a
polypeptide monomer at least of a given % identity to a recited
reference amino acid sequence i.e., SEQ ID NOS: 142, 143,
144[,] and 145, one cannot envision which of these also encode
a polypeptide with a specified activity in the context of the
polyligand structure X-S-X or X-S-Y.
(Id. at 17.)
Appeal 2012-005519
Application 11/834,897

6
FF 13. Examiner finds that Appellant’s Specification fails to disclose “how
the linker segments in the context of a polyligand comprising the claimed
variants of inhibitory peptides interact with particular PKAc [(protein kinase
A catalytic subunit)] sites” (id. at 18).
FF 14. Examiner finds that “excessive trial and error experimentation would
have been required to identify” a polynucleotide that encodes a polypeptide
that inhibits protein kinase A activity as set forth in Appellant’s claimed
invention (id. at 18-19).
FF 15. Appellant discloses that “[i]hibition of PKA activity is demonstrated
by measuring phosphorylation of endogenous substrates against controls”
(Spec. 21: ¶ [0079]).
FF 16. Kimchi-Sarfaty discloses that
The amino acid sequence of proteins is generally
believed to determine protein expression, folding, and function;
mutations that alter the primary structure of a protein can affect
these properties. The important question addressed by this
study is the role of silent mutations (i.e., those that do not affect
amino acid sequence) in protein folding and function. Recent
theoretical studies have suggested that codon usage is not
random, and experimental studies in prokaryotes suggest that
this may be so. Here we show that a silent mutation in a
complex, mammalian membrane transport protein alters the
substrate specificity. We hypothesize that when frequent
codons are changed to rare codons in a cluster of infrequently
used codons, the timing of cotranslational folding is affected
and may result in altered function.
(Kimchi-Sarfaty4 527: col. 3, ll. 36-53 (endnotes omitted); see generally
Ans. 13-16.)

4 Chava Kimchi-Sarfaty, et al., “A ‘Silent’ Polymorphism in the MDR1
Gene Changes Substrate Specificity,” 315 SCIENCE 525-528 (2007).
Appeal 2012-005519
Application 11/834,897

7
ANALYSIS
Initially, we note that there is some confusion on this record as to the
exact scope of the claims before this Panel for review (see, e.g., Ans. 6
(While the claims before this Panel for review are drawn to polynucleotides,
Examiner states that “[t]he claims are rejected to the extent that the[y] read
on the elected species: the polypeptide of SEQ ID NO: 1”); Cf. App. Br. 14).
Nevertheless, during the November 14, 2013 Oral Hearing, Appellant’s
representative confirmed that the full scope of Appellant’s claimed invention
is before this Panel for review.

Claim Interpretation:
Appellant’s claims 166 and 176 are directed to: (1) a polynucleotide
of any sequence and length (2) that encodes a polypeptide of any length, (3)
wherein the polypeptide includes within its sequence (4) at least one region
represented by the formula X-S-X or X-S-Y and (5) any number of
additional molecules (e.g., an epitope tag, reporter, cellular localization
signal, X or Y monomers, and spacers (S)) attached to the polypeptide in
some manner (FF 4-6; Claims 166 and 176).
Appellant defines the components of the X-S-X and X-S-Y formulas
as a polypeptide monomer (a) of any length that (b) contains an amino acid
sequence at least 85% (claim 166) or 98% (claim 176) identical to any one
of SEQ ID NOS: 55-216, wherein (c) “Y” is a different polypeptide
monomer than “X,” and (d) the Xaa recited in SEQ ID NOS: 55-216
represents a naturally or non-naturally occurring amino acid (FF 5 and 6;
Claims 166 and 176).
Appeal 2012-005519
Application 11/834,897

8
The “S” component of Appellant’s formula is (i) optionally present
and (ii) may be of any length and composition (FF 8; Claims 166 and 176).
According to Appellant’s Specification, variants of SEQ ID NOS: 55-
216 may be combined in any number of ways and with any number of
additional molecules of any length to realize the intended scope of
Appellant’s claimed invention, which is “to capture all combinations of
homopolyligands and heteropolyligands without limitation” (FF 3 and 7;
Claims 166 and 176).
The remaining limitation of Appellant’s claimed invention requires
the foregoing highly variable polynucleotide to encode a polypeptide that
inhibits at least one isoform of protein kinase A activity (FF 2; Claims 166
and 176).

Representative Species:
Appellant discloses three heteropolyligands that fall within the scope
of Appellant’s claimed invention and comprise a structure having the
formula, A-S1-B-S2-C-S3-D; X-S4-Y-S5-Z; and X-S6-Y-S7-Z-S8-A-S9-B
(FF 9). Appellant fails to identify which protein kinase A isoform is
inhibited by the representative heteropolyligands (see FF 9; Cf. FF 2 and
15). Instead, Appellant discloses that “[i]hibition of PKA activity is
demonstrated by measuring phosphorylation of endogenous substrates
against controls” (FF 15).

Written Description:
Examiner finds that Appellant’s Specification fails to provide written
descriptive support for the genus of isolated nucleic acid sequences,
Appeal 2012-005519
Application 11/834,897

9
encompassed by Appellant’s claims 166 and 176, that encode a polypeptide
that inhibits the activity of at least one isoform of protein kinase A (FF 10;
see also FF 2). According to Examiner, “one cannot envision which of the
[highly variable polynucleotides encompassed by Appellant’s claimed
invention] encode[s] a polypeptide with a specified activity in the context of
the polyligand structure X-S-X or X-S-Y (FF 12 (emphasis added)). In this
regard, Examiner finds that variability in both nucleic acid and amino acid
sequence contribute to the unpredictability associated with protein
functionand Appellant failed to disclose a “core structure” that is
representative of the “full scope of the claimed genera” (FF 11, 13, and 16).

Claim 166:
Appellant contends that because it would have been obvious to make
and test a polynucleotide within the genus of Appellant’s claimed invention,
Appellant had possession of every polynucleotide sequence contained
therein that is capable of inhibiting the activity of at least one protein kinase
A isoform (App. Br. 15-16; FF 2). We are not persuaded. “[A] description
that merely renders the invention obvious does not satisfy the requirement.”
Ariad Pharmaceuticals, Inc. v. Eli Lilly and Co., 598 F.3d 1336, 1352 (Fed.
Cir. 2010) (en banc).
Appellant contends that the law does not require a correlation between
structure and function (App. Br. 25). While we agree with Appellant in that
the written description requirement of 35 U.S.C. § 112, first paragraph, may
be satisfied in a number of ways, the Specification must “itself …
demonstrate[s] possession” of the claimed invention. Ariad, 598 F.3d at
1352. For the reasons set forth above, Appellant’s Specification fails to
Appeal 2012-005519
Application 11/834,897

10
demonstrate possession of the entire claimed genus of polynucleotides that
encode a protein that is capable of inhibiting the activity of at least one
isoform of protein kinase A. For the same reasons, we are not persuaded by
Appellants’ contention that “one need not disclose what amino acid
modifications are permissible” (App. Br. 25; Cf. FF 16).
We recognize, but are not persuaded by, Appellant’s reliance on
Example 14 of the “REVISED INTERIM WRITTEN DESCRIPTION
GUIDELINES TRAINING MATERIALS” (see e.g. App. Br. 16-19 and 25-
26; see also Appellant’s Exhibit A). Appellant’s contentions fail to account
for the revised “TRAINING MATERIALS”5 dated prior to the filing date of
Appellant’s Briefs.
We recognize, but are not persuaded by, Appellant’s contention that
Examiner’s written description rejection is contrary to Federal Circuit Case
Law (App. Br. 19-22). See e.g., Ariad; see also University of Rochester v.
G.D. Searle & Co., Inc., 358 F.3d 916, 925 (Fed. Cir. 2004) (“[e]ven with
the three-dimensional structures of enzymes such as COX-1 and COX-2 in
hand, it may even now not be within the ordinary skill in the art to predict
what compounds might bind to and inhibit them”). Simply stated, contrary
to the disclosure set forth in Appellant’s Specification and Appellant’s
contentions, the written description requirement “requires a description of an
invention, not an indication of a result that one might achieve if one made
that invention.” Regents of the University of California v. Eli Lilly & Co.,
119 F.3d 1559, 1568 (Fed. Cir. 1997); see also Novozymes A/S v. DuPont

5 “WRITTEN DESCRIPTION TRAINING MATERIALS,” 33-35,
(Revision 1, March 25, 2008) (see http://www.uspto.gov/web/menu/
written.pdf).
Appeal 2012-005519
Application 11/834,897

11
Nutrition Biosciences APS, 723 F.3d 1336, 1350 (Fed. Cir. 2013) (“A patent
… ‘is not a reward for the search, but compensation for its successful
conclusion.’ … For that reason, the written description requirement
prohibits a patentee from ‘leaving it to the … industry to complete an
unfinished invention.’” (citations omitted)).

Claim 176:
We recognize Appellant’s contention that Appellant’s Specification
provides written descriptive support for the genus encompassed by
Appellant’s claim 176, because the recited monomers “are at least 98%
identical to SEQ ID NOS: 55-216” (App. Br. 26-27). We are not persuaded
for the reasons set forth above. To be clear, as discussed above, the claimed
polynucleotide comprises any number of different components that vary,
inter alia, in size, composition, and sequence, in addition to at least two
monomer units that vary to some degree relative to the recited SEQ ID NOS.

Enablement:
Examiner finds that Appellant’s Specification fails to provide an
enabling description of the genus of isolated nucleic acid sequences, as set
forth in Appellant’s claims 166 and 176, that encode a polypeptide able to
inhibit the activity of at least one isoform of protein kinase A (FF 11; see
also FF 2). Examiner finds that “excessive trial and error experimentation
would have been required to identify” a polynucleotide that encodes a
polypeptide that inhibits protein kinase A activity as set forth in Appellant’s
claimed invention (FF 14).

Appeal 2012-005519
Application 11/834,897

12
Claim 166:
“Appellants submit that one of ordinary skill in the art would be able
to make and derive the claimed isolated polynucleotide of claim 166 based
on the specification as filed” (App. Br. 32). Appellant’s claims are not,
however, limited to a polynucleotide that encodes a protein. Instead,
Appellant’s claims require the polynucleotide to encode a protein that
inhibits the activity of at least one protein kinase A isoform (see, e.g., FF 2
and 13).
Appellant’s Specification fails to disclose which polypeptides
encoded by a polynucleotide, within the scope of Appellant’s claimed
invention, would be capable of inhibiting the activity of at least one protein
kinase A isoform or, if not all isoforms, which particular isoform such an
encoded polypeptide would inhibit. At best, Appellant’s Specification
directs one to make polynucleotides that fall within the extremely large
scope of Appellant’s claim and then figure out, through trial and error
testing, which of these polynucleotides encode a polypeptide capable of
inhibiting the activity of at least one protein kinase A isoform (see FF 15).
As Examiner explains, this activity would require “excessive trial and error
experimentation” (FF 14). See In re ʼ318 Patent Infringement Litigation,
583 F.3d 1317, 1327 (Fed. Cir. 2009) (“[A]t the end of the day, the
specification, even read in light of the knowledge of those skilled in the art,
does no more than state a hypothesis and propose testing to determine the
accuracy of that hypothesis. That is not sufficient.”).
We acknowledge Appellant’s concession that “it would . . . require[]
experimentation in order to modify the claimed polynucleotide to encode a
PKA ligand across the full scope of the claims” (Reply Br. 18). See In re
Appeal 2012-005519
Application 11/834,897

13
Vaeck, 947 F.2d 488, 495 (Fed. Cir. 1991) (“That some experimentation may
be required is not fatal; the issue is whether the amount of experimentation
required is ‘undue.’”) However, notwithstanding Appellant’s contention to
the contrary, we agree with Examiner’s conclusion that making and testing
every possible species that falls within the scope of Appellant’s claimed
invention to identify those polynucleotides that encode a polypeptide
exhibiting the claimed activity would require undue experimentation (See
Ans. 20 and 28-29; Cf. Reply Br. 18;). “[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.’”
Genentech, Inc. v. Novo Nordisk, A/S, 108 F.3d 1361, 1365 (Fed. Cir. 1997)
(quoting In re Wright, 999 F.2d 1557, 1561 (Fed. Cir. 1993)).

Claim 176:
We recognize Appellant’s contention that Appellant’s Specification
provides written descriptive support for the genus encompassed by
Appellant’s claim 176, because the recited monomers “are at least 98%
identical to SEQ ID NOS: 55-216” (App. Br. 33-34). We are not persuaded
for the reasons set forth above.

CONCLUSION OF LAW
The preponderance of evidence on this record supports Examiner’s:
1. finding that Appellant’s Specification fails to provide written
descriptive support for the full scope of Appellant’s claimed invention; and
2. conclusion that undue experimentation would be required to
practice the full scope of claimed invention.
Appeal 2012-005519
Application 11/834,897

14
The rejection of claims 166 and 176 under the written description and
enablement provisions of 35 U.S.C. § 112, first paragraph is affirmed.
Claims 167-170, 174, and 175 fall together with claim 166.

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).

AFFIRMED

lp