Ex Parte Stout et al

Patent Trial and Appeal Board

Oct 24, 2018

13511267 (P.T.A.B. Oct. 24, 2018)

UNITED STA TES p A TENT AND TRADEMARK OFFICE
APPLICATION NO. FILING DATE
13/511,267 10/05/2012
52034 7590 10/26/2018
Parker Highlander PLLC
1120 South Capital of Texas Highway
Bldg. 1, Suite 200
AUSTIN, TX 78746
FIRST NAMED INVENTOR
J. Timothy Stout
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
ATTORNEY DOCKET NO. CONFIRMATION NO.
CLFR.P0333US 3427
EXAMINER
MARTINEZ, TARA L
ART UNIT PAPER NUMBER
1654
NOTIFICATION DATE DELIVERY MODE
10/26/2018 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):
docket@phiplaw.com
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
BEFORE THE PATENT TRIAL AND APPEAL BOARD
Ex parte J. TIMOTHY STOUT, BINOY APPUKUTTAN, and
TREVORMCFARLAND 1
Appeal2017-004259
Application 13/511,267
Technology Center 1600
Before ERIC B. GRIMES, JOHN G. NEW, and JOHN E. SCHNEIDER,
Administrative Patent Judges.
GRIMES, Administrative Patent Judge.
DECISION ON APPEAL
This is an appeal under 35 U.S.C. § 134(a) involving claims to a
recombinant polypeptide, which have been rejected for lack of adequate
written description. We have jurisdiction under 35 U.S.C. § 6(b ).
We affirm.
STATEMENT OF THE CASE
"Ichthyosis vulgaris and atopic dermatitis are ... associated with one
of the most common single-gene disorders in humans, a disorder of the
1 Appellants identify the Real Party in Interest as Research Development
Foundation. Appeal Br. 3.
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Application 13/511,267
filaggren [ sic, filaggrin] (FLG) gene." Spec. 1 :22-23. The "filaggrin protein
... [is] essential for proper keratinization and squamification of epithelial
cells, formation of epidermal barrier, and hydration." Id. at 1 :26-27.
"Despite the information available concerning FLG and its role in skin
disease, there is a need for more effective methods of treating diseases or
disorders of the skin." Id. at 2:4--5.
"The present invention is in part based on the finding that the uptake
of a filaggrin polypeptide into a cell can be surprisingly and effectively
enhanced by attaching a cell importation signal sequence to the filaggrin
polypeptide." Id. at 2:8-10.
Any cell importation signal sequence that facilitates entry of a
filaggrin amino acid sequence into a cell is contemplated as a
cell importation signal sequence of the present invention. In
some embodiments, the signal sequence includes a motif of two
to fifteen amino acids, wherein the motif includes at least one
arginine amino acid residue and at least one methionine amino
acid residue.
Id. at 13:3-9.
Claims 1--4, 7-18, and 20-30 are on appeal. Claim 1 is illustrative and
reads as follows:
1. A recombinant polypeptide comprising (a) a filaggrin
amino acid sequence; and (b) a cell importation signal sequence
comprising a motif of two to fifteen amino acids, wherein the
motif comprises at least one arginine residue and at least one
methionine residue.
DISCUSSION
The Examiner has rejected claims 1--4, 7-18, and 20-30 under 35
U.S.C. § 112, first paragraph, for lack of adequate written description. The
Examiner finds that the genera recited in claim 1 include "filaggrin amino
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acid sequences ... obtained from any source and from any species," as well
as a "cell importation signal sequence that facilities [sic] entry of the
filaggrin amino acid sequence into a cell." Ans. 4 (citing Spec. 12-13). The
Examiner finds that the Specification describes two species of the
recombinant polypeptides encompassed by claim 1, as well as nineteen full-
length filaggrin sequences from different species and sixteen cell
importation signal sequences. Id. at 5.
The Examiner finds that "the disclosure of SEQ ID NOs: 1-19 are not
representative of the genus of filaggrin polypeptides." Id. at 6. The Examiner
finds that "the genus is enormous" and "the filaggrin amino acid sequence of
claim 1 can be any portion/fragment of filaggrin, comprising at least 2 amino
acids at any position." Id. at 6-7. The Examiner finds that "the disclosure of
SEQ ID NO: 1-19 is not representative of the genus, because the genus of
filaggrin polypeptides can vary widely." Id. at 7.
The Examiner cites Rothnagel 2 as evidence that "mouse and rat
filaggrins are very similar at both the nucleic acid and amino acid level,
however the mouse and human filaggrins have almost no sequence
homology." Id. The Examiner cites Kanda3 as evidence that "there is little
homology between canine, human and mouse filaggrin proteins[']
structure." Id.
The Examiner also finds that "the disclosure of 16 cell importation
motif[s] is not representative of the full scope of the claim." Id. at 8.
2 Rothnagel et al., The Structure of the Gene for Mouse Filaggrin and a
Comparison of the Repeating Units, 265 J. Biol. Chem. 1862-1865 (1990).
3 Kanda et al., Characterization of canine filaggrin: gene structure and
protein expression in dog skin, 24 Vet. Dermatol. 25-e7.
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Application 13/511,267
"Importantly, all but one of the SEQ ID NOs of cell importation signals
presented in Table 3, do not meet the limitations of claim 1. For example,
SEQ ID NO: 24-38 do[] not comprise a single methionine residue, which is
required by claim 1." Id. The Examiner points out that "the species
presented in the instant Specification only represent[] cell importation tags
of 10-15 amino acids" and cites Lindgren 4 as a review of cell importation
peptides that shows "the shortest cell-importation peptide being 10 amino
acids in length." Id. The Examiner concludes that "the skilled artisan would
not reasonably conclude that the inventor(s), at the time the application was
filed, had possession of the full scope of the claimed invention." Id. at 10.
We agree with the Examiner that the Specification does not provide a
written description of either the filaggrin component or the cell importation
signal sequence component of the claimed polypeptide sufficient to show
possession of the full genus of the claimed product.
"[T]he test for sufficiency [ of the written description] is whether the
disclosure of the application relied upon reasonably conveys to those skilled
in the art that the inventor had possession of the claimed subject matter as of
the filing date." Ariad Pharms., Inc. v. Eli Lilly & Co., 598 F.3d 1336, 1351
(Fed. Cir. 2010) (en bane). "[T]he test requires an objective inquiry into the
four comers of the specification from the perspective of a person of ordinary
skill in the art. Based on that inquiry, the specification must describe an
invention understandable to that skilled artisan and show that the inventor
actually invented the invention claimed." Id.
4 Lindgren et al., Cell-penetrating peptides, 21 TiPS 99-103 (2000).
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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." Id.
at 1350. In addition, "functional claim language can meet the written
description requirement when the art has established a correlation between
structure and function." Id.
Here, claim 1 recites two genera of amino acid sequences: 1) "a
filaggrin amino acid sequence," and 2) "a cell importation signal sequence
comprising a motif of two to fifteen amino acids, wherein the motif
comprises at least one arginine residue and at least one methionine residue."
With respect to filaggrin sequences, the Specification states that "FLG is a 3-
exon gene located in the Epidermal Differentiation Complex (EDC) on
chromosome 1 q21." Spec. 1 :24--25. The Specification describes the structure
(amino acid sequence) of nineteen filaggrin proteins: five from humans,
eight from mice, two each from chimpanzees and macaques, and one each
from rats and cows. Id. at 12-13 (Table 2).
Table 2 itself is thus evidence that the sequence of filaggrin is variable
even within a particular species. In addition, Rothnagel provides evidence
that the sequence (structure) of filaggrin is not conserved between species.
Rothnagel states that "filaggrins from several species have been
characterized" and "differences had been noted in their size, amino acid
composition, and immunogenic cross-reactivity." Rothnagel 1862, right col.
Rothnagel also states that "[ m ]ouse and rat filaggrins are very similar at both
the nucleic acid and amino acid levels; however, in contrast, mouse and
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Application 13/511,267
human filaggrins have almost no sequence homology." Id. (reference
citations omitted)
In addition, Kanda discloses that filaggrins from humans, dogs, and
mice have different structures. 5 Kanda discloses that the filaggrins from
these three species differ in the size of their N-terminal and C-terminal
regions, and in both the size and number of the FLG repeat units making up
the proteins' sequences. Kanda 27 (Table 1 ). Kanda discloses, in fact, that
even human filaggrins vary in the size of the repeat unit (324--325 amino
acids) and in the number of repeat units in the protein (from 10 to 12). Id.
"Appellants consider Kanda to strongly support their position"
because it shows that "filaggrin is well studied in a significant number of
species." Appeal Br. 32. The passage quoted by Appellants, however,
discusses filaggrins only from humans, dogs, and mice, which-as shown in
Kanda's Table !--differ significantly in structure. The passage relied on by
Appellants confirms what is shown in Table 1, because it states that
[t]he gene structure and architecture of FLG has been reported
in humans and mice. These studies showed that N-terminal and
C-terminal regions of proFLG were conserved but the number
and length of the FLG monomers differed between humans and
mice. It has been suggested that amino acid sequences of FLG
monomers are highly variable in mammals.
Kanda 25, right col.
5 Appellants argue that Kanda cannot properly be relied upon because it was
published after the filing date of the instant application and "written
description looks at the understand[ing] of those of skill as of the filing
date." Appeal Br. 11. However, "the use of post-priority date evidence to
show that a patent does not disclose a representative number of species of a
claimed genus is proper." Amgen, Inc. v. Sanofi, 872 F.3d 1367, 1375 (Fed.
Cir. 2017).
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Thus, the evidence of record supports the Examiner's conclusion that
the nineteen filaggrin sequences, from six mammalian species, that are
described in the Specification are not representative of the structure of the
full genus of filaggrins that are encompassed by claim 1.
The evidence of record also supports the Examiner's position that the
Specification does not describe a structure/function correlation that would
provide an adequate written description of the genus. 6 Specifically,
Rothnagel discloses that "filaggrins from several species have been
characterized and shown to be both functionally and biochemically similar"
even though they differ in "size, amino acid composition, and immunogenic
cross-reactivity." Rothnagel 1862, right col. Rothnagel also states that
"mouse and human filaggrins have almost no sequence homology." Id.
Rothnagel thus provides evidence that, even though filaggrins from different
mammalian species are functionally similar, they do not share a common
structure that correlates with that function.
In summary, we agree with the Examiner that the Specification does
not disclose a representative number of filaggrin structures, and does not
describe a correlation between the filaggrin structure and its function. Thus,
the Specification does not provide an adequate written description of the
filaggrin amino acid sequences that are encompassed by claim 1.
6 We do not, however, agree with the Examiner that the relevant function
with respect to claim 1 is treating a skin disease or disorder. Ans. 9. Claim 1
is simply directed to a recombinant polypeptide, not a method of treatment.
The relevant function, therefore, is that of a native filaggrin protein. Whether
a skilled artisan would know how to use the claimed polypeptide, for
treatment or otherwise, might raise an issue of enablement but it is not
relevant to the adequacy of the written description.
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Application 13/511,267
The Specification also does not provide an adequate written
description of the genus of cell importation signal sequences that are
encompassed by claim 1, which requires that: 1) the sequence "facilitates
entry of a filaggrin amino acid sequence into a cell" (Spec. 13:3--4) and
2) the sequence comprises a motif of 2-15 amino acids, which include at
least one arginine (Arg or R) and at least one methionine (Met or M).
The Specification describes the sequences of sixteen cell importation
signal sequences. Spec. 13-14 (Table 3). As the Examiner pointed out (Ans.
8), however, only one of these sequences includes an arginine and a
methionine. The Specification thus describes only a single species within the
genus of cell importation signal sequences recited in claim 1.
Appellants point to Lindgren as evidence that other "cell penetrating
peptides ... were known in the art in 2000, including RMR type sequences
('penetratin,' Table 2, p. 100)." Appeal Br. 14. Lindgren indeed discloses, in
a review of cell-penetrating peptides, that penetratin was one such peptide
and includes an arginine (R) and a methionine (M). Lindgren 100 (Table 2).
None of the other cell-penetrating peptides described by Lindgren, however,
includes a methionine. Thus, Lindgren is evidence that those skilled in the
art knew of one other cell importation signal sequence meeting the
requirements of claim 1, bringing to two the total number of such sequences
that were known in the art or described in the Specification.
Appellants also point to Wender 7 as evidence supporting their
position. Appeal Br. 14--15. Appellants argue that Wender
is particularly relevant in that it discloses and claims RMR
based cell importation sequences directly relevant to the RMR
7 Wender et al., U.S. Patent 7,585,834 B2, issued Sept. 8, 2009.
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peptide sequences used in the present invention, which is
evident upon a review of claim 1 or Figs. 2-4, for example of
the Wender patent. See, for example, ' [ t ]he transport moiety
includes a structure selected from the group consisting of
(ZYZ)nZ, (ZY)nZ, (ZYY)nZ and (ZYYY)nZ. Subunit "Z" is L-
arginine or D-arginine, and subunit "Y" is an amino acid that
does not comprise an amidino or guanidino moiety.' Col. 2,
lines 17-22. We note that methionine is specifically taught to be
a 'Y' residue - see claim 2.
Id. at 15.
Wender does indeed disclose arginine-containing transport moieties,
and Wender' s claim 2 states that the Y component can be methionine - or
any other naturally occurring amino acid, as well as hydroxyproline, y-
amino butyric acid, B-alanine, sarcosine, or E-amino caproic acid. Wender
48:61---67 (claim 2). We therefore are not persuaded that Wender provides
evidence that cell importation signal sequences comprising both an arginine
residue and a methionine residue were known in the art.
In summary, we agree with the Examiner that the Specification does
not disclose a representative number of cell importation signal sequences
comprising a motif including an arginine residue and a methionine residue,
and the evidence of record does not show that such cell importation signal
sequences were known in the art as of the filing date of the instant
application. We therefore conclude that the Specification does not describe
either of the components of the claimed recombinant polypeptide in a
manner that satisfies the written description requirement of 35 U.S.C. § 112,
first paragraph.
Appellants argue that
[t]he Sandilands reference is basically a review article
presenting an overview in exceeding detail of profilaggrin
structure (p. 1285-6), control of FLG gene expression (p. 1286-
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7), the role of the N and C- terminal domains and a detailed
structure of the various domains and repeats ( exemplified in
mouse, rat and human; Fig. 2) (p. 1287), phosphorylation and
post-translational processing (p. 1288-91), and so forth.
Appeal Br. 13.
We have reviewed Sandilands but do not agree with Appellants'
apparent position that the structure of the genus of filaggrin proteins was
known in the art. Sandilands was published shortly before Appellants filed
the provisional application to which Appellants claim benefit, and thus
represents the state of the art as of Appellants' filing date.
Sandilands "focus[ es] on what is currently known about filaggrin
biology and its role in epidermal differentiation and skin barrier formation as
well as discussing its relevance to human disease." Sandilands 1285, right col.
Sandilands shows a general structure for profilaggrin, which includes "10-12
filaggrin repeats flanked by two partial repeats" as well as N-terminal and C-
terminal domains. Id. at 1286, Fig. lB. Sandilands also provides the sequences
for the linker regions connecting the filaggrin repeats in the mouse, rat, and
human proteins. Id. at 1286, Fig. 1 C.
Sandilands does not, however, describe the structure ( amino acid
sequence) of the filaggrin repeats making up the profilaggrin polypeptide,
nor does it provide any basis for doubting the disclosures of Rothnagel and
Kanda, showing that the amino acid sequences of filaggrin proteins from
different species differ significantly. We therefore conclude that a
preponderance of the evidence of record supports a conclusion that the
limited number of filaggrin species that are described in the Specification are
not representative of the full scope of the genus of filaggrin proteins, and
that no structure/function correlation is described for filaggrin proteins.
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With regard to the cell importation signal sequence recited in claim 1,
in addition to the arguments discussed above, Appellants argue that "[ w ]hile
it is true that the only example of an RMR sequence per se is SEQ ID
N0:23, the specification includes a detailed discussion and description of
RMR sequences and provides evidence that such sequences are well known
(e.g., Datar et al., Nucleic Acids Res., 21(3):439-446, 1993)." Appeal Br. 17.
However, Appellants do not specify if or when Datar was made of
record during prosecution, and we were unable to find it in reviewing the file
history. We therefore have not considered Datar.
For the reasons discussed above, we affirm the rejection of claim 1
under 35 U.S.C. § 112, first paragraph. Claims 2--4, 7-18, and 20-27 have
not been argued separately and therefore fall with claim 1. 3 7 C.F .R.
§ 4I.37(c)(l)(iv).
With regard to claims 28-30, Appellants argue that these claims
require, respectively, a natural filaggrin amino acid sequence, a mammalian
filaggrin amino acid sequence, or a human filaggrin amino acid sequence.
Appeal Br. 17-18. Appellants argue that "[e]ach of these claims presents a
separate issue of written description that the Action has not even attempted
to address, much less provide a prima facie rejection for lack of written
description." Id. at 18.
In response, the Examiner clarified that these claims were rejected
under 35 U.S.C. § 112, first paragraph, because the Specification does not
adequately describe the cell importation signal sequence required in the
claimed recombinant polypeptide. Ans. 24. For the reasons discussed above,
we agree with the Examiner's conclusion. We therefore affirm the rejection
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of claims 28-30 under 35 U.S.C. § 112, first paragraph, for lack of adequate
written description.
SUMMARY
We affirm the rejection of claims 1--4, 7-18, and 20-30 under 35
U.S.C. § 112, first paragraph, for lack of adequate written description.
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
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