Ex Parte Gibbs

Patent Trial and Appeal Board

Oct 26, 2018

13657625 (P.T.A.B. Oct. 26, 2018)

UNITED STA TES p A TENT AND TRADEMARK OFFICE
APPLICATION NO. FILING DATE
13/657,625 10/22/2012
23579 7590 10/26/2018
Pabst Patent Group LLP
1545 PEACHTREE STREET NE
SUITE 320
ATLANTA, GA 30309
FIRST NAMED INVENTOR
Phillip Gibbs
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.
DECI 100 1095
EXAMINER
FOSTER, CHRISTINE E
ART UNIT PAPER NUMBER
1641
MAIL DATE DELIVERY MODE
10/26/2018 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 PHILLIP GIBBS
Appeal2017-002530
Application 13/657 ,625 1
Technology Center 1600
Before DONALD E. ADAMS, RY ANH. FLAX, and DAVID COTTA,
Administrative Patent Judges.
COTT A, Administrative Patent Judge.
DECISION ON APPEAL
This is an appeal under 35 U.S.C. § 134 involving claims to a kit for
performing a non-competitive assay for an analyte. The Examiner rejected
the claims on appeal under 35 U.S.C. § l 12(a) for failure to comply with the
written description requirement, under 35 U.S.C. § l 12(b) as indefinite for
failing to particularly point out and distinctly claim the subject matter that
the inventor regards as the invention, and under 35 U.S.C. § 103(a) as
obvious.
We affirm.
1 According to Appellant, the real party in interest is "Decimadx, LLC."
App. Br. 2.
Appeal2017-002530
Application 13/657,625
STATEMENT OF THE CASE
The Specification discloses that "[a] point-of-care assay has been
developed for quantitatively measuring the amount of a small analyte in a
biological sample from a subject." Spec. 3. "[I]n preferred embodiments,
the assay is a non-competitive immunoassay, which typically involves the
use of a binding agent and a capture agent that simultaneously bind the
analyte in a sandwich assay." Id. "In some embodiments, the non-
competitive assay involves the use of a 'binding agent' that selectively binds
the analyte, forming a 'capture complex' of the binding agent and the
analyte, and a 'capture agent' that selectively binds the capture complex but
not free analyte, forming a 'sandwich complex."' Id. at 3--4. "In these
embodiments, the amount of sandwich complex is directly related to the
amount of analyte in the sample." Id. at 4.
Claims 1 7-21 are on appeal. Claim 17 is illustrative and reads as
follows:
17. A kit for performing a non-competitive assay for an
analyte selected from the group consisting of a hormone, drug,
or drug metabolite having a molecular weight of less than 2,000
Daltons,
wherein the kit comprises a membrane strip comprising
an application point, a capture zone, and an absorbent zone,
wherein the capture zone comprises an aptamer that
selectively binds to a binding agent-analyte complex but not
free analyte, immobilized in or on the membrane strip, and
wherein the aptamer comprises nucleic acid aptamer, or
peptide aptamer.
App. Br. 30 (Claim App'x).
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The claims stand rejected as follows.
Claims 17-21 were rejected under 35 U.S.C. § 112 for failure to
comply with the written description requirement.
Claim 21 was rejected under 35 U.S.C. § 112 as indefinite.
Claims 17-19 and 21 were rejected under 35 U.S.C. § I03(a) as
obvious over the combination of Pulli, 2 Kondou, 3 Fitzpatrick4 and Schultz. 5
Claim 20 was rejected under 35 U.S.C. § I03(a) as obvious over the
combination of Pulli, Kondou, Fitzpatrick, Schultz, and Wang. 6
Claims 17-21 were rejected under 35 U.S.C. § I03(a) as obvious over
the combination of Pulli, Kondou, Fitzpatrick, Schultz, and Wang.
FINDINGS OF FACT
We adopt the Examiner's findings of fact as set forth in the Final
Action and Answer. We set forth the following findings to highlight certain
evidence.
1. The Examiner finds, and Appellant does not dispute, that the
Specification "does not contain any actual reduction to practice of any
aptamer having the necessary functional characteristics." Final Act. 13;
App. Br. 8-9.
2. The Examiner finds, and Appellant does not dispute, that the
Specification does not disclose "any partial structure common to the
2 Pulli et al., US Patent No. 7,749,712 B2, issued July 6, 2010 ("Pulli").
3 Kondou et al., WO 2011/010673 Al, published Jan. 27, 2011 ("Kondou").
Kondou is not an English language document. All citations to Kondou are
to its counterpart, US 2011/0195438 Al.
4 Fitzpatrick et al., US Patent No. 5,451,504, issued Sept. 19, 1995
("Fitzpatrick").
5 Schultz et al., WO 2008/070865 A2, published June 12, 2008 ("Schultz").
6 Wang et al., US Patent No. 7,638,093 B2, issued Dec. 29, 2009 ("Wang").
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members of the genus of aptamers that would correlate with function." Final
Act. 4.
3. The inventor, Dr. Gibbs states: "[B]inding affinities for many
small molecule aptamers are in the micro and millimolar range, ranges that
would not be clinically useful in a non-competitive binding assay." Gibbs
Decl. 7 i-f 7.
4. The Specification states: "The term 'aptamer' refers to an
oligonucleic acid or peptide molecule that binds to a specific target
molecule. Aptamers are generally selected from a random sequence pool.
The selected aptamers are capable of adapting unique tertiary structures and
recognizing target molecules with high affinity and specificity." Spec. 10.
5. The Specification states: "A 'nucleic acid aptamer' is an
oligonucleic acid that binds to a target molecule via its conformation. A
nucleic acid aptamer may be constituted by DNA, RNA, or a combination
thereof. Nucleic acid aptamers are typically engineered using SELEX
(systematic evolution of ligands by exponential enrichment)." Id.
6. The Specification states: "A 'peptide aptamer' is a
combinatorial peptide molecule with a randomized amino acid sequence that
is selected for its ability to bind a target molecule. Peptide aptamers are
typically selected from combinatorial peptide libraries using yeast two-
hybrid or phage display assays." Id.
7. The Specification states: "[T]he term 'analyte' refers to a
chemical substance of interest that is a potential constituent of a biological
sample and is to be analyzed by an assay." Id. at 8.
7 Declaration of Dr. Phillip Gibbs Under 37 C.F.R. § 1.132, signed March 8,
2016 ("Gibbs Deel.").
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Application 13/657,625
8. The Specification states:
The term "binding agent" refers to a compound that specifically
binds to an analyte. The term "capture agent" refers to an
immobilized compound that selectively binds analyte
complexed with binding agent ( capture complex) or free
binding agent (as a control) .... Binding agents and capture
agents include antibodies, nucleic acid aptamers, and peptide
aptamers.
Id. at 9.
9. The Specification states: "The term 'capture complex' refers to
a complex formed by the specific binding of a binding agent to an analyte."
Id.
10. The Specification states: "There may be specialized examples
where aptamers ( employed alone) have been shown to recognize small
molecules, however, in general, the binding affinity is poor and ability to
evolve aptamers against all small molecules targets of interest has proved
elusive." Id. at 12.
11. The Specification states:
While not being bound by theory, the sandwich assays
described herein "converts" small molecules which are in
general poor targets for aptamers into proteins targets which are
much better (i.e. nanomolar affinities compared to micromolar)
targets. An immunocomplex of antibody and target molecule
for example, represent a much richer target for aptamer binding.
Evolving aptamers against the much richer binding target of the
immunocomplex between antibodies and the target molecules is
a much more generalizable strategy (i.e. no special label
required for each target molecule for immobilization as the
antibodies already present a generalizable handle for the
required immobilization).
Id. at 13.
12. The Specification states: "Nucleic acid aptamers are typically
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Application 13/657,625
isolated from complex libraries of synthetic oligonucleotides by an iterative
process of adsorption, recovery and reamplification. For example, nucleic
acid aptamers may be prepared using the SELEX (Systematic Evolution of
Ligands by Exponential Enrichment) method." Id. at 22.
13. The Specification states: "Peptide aptamer selection can be
made using different systems, but the most used is currently the yeast two-
hybrid system. Peptide aptamer can also be selected from combinatorial
peptide libraries constructed by phage display and other surface display
technologies such as mRNA display; ribosome display, bacterial display and
yeast display." Id. at 24.
14. Pulli discloses:
A non-competitive immunoassay for small analytes, wherein
the analyte is reacted with two binding partners. The first
binding partner binds to the analyte to form a complex between
the first binding partner and the analyte, and the second binding
partner binds to the complex formed by the first binding partner
and the analyte. The resulting complex formed between the
analyte and the binding partners is detected.
Pulli Abstract.
15. Schultz discloses that "[a]ptamers have the capacity for forming
specific binding pairs with virtually any chemical compound, whether
monomeric or polymeric." Schultz 35.
16. Schultz discloses lateral flow assays and teaches that "[i]n one
embodiment, the binding agents are monoclonal or polyclonal antibodies
that are immuno-specific for the target molecules to be detected. In another
embodiment, the binding agents are DNA aptamers that are specific for
target nucleic acid molecules or other molecules to be detected." Id. at 18;
see also id. ( disclosing that binding agents are "e.g., monoclonal antibodies
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or DNA aptamers"); and id. at 19 ("the conjugate zone, ... contains free
binding agents (e.g., monoclonal antibodies or DNA aptamers) specific for
different target molecules").
WRITTEN DESCRIPTION
A description adequate to satisfy 35 U.S.C. § 112, first paragraph,
must "'clearly allow persons of ordinary skill in the art to recognize that [the
inventor] invented what is claimed.'" Ariad Pharms., Inc. v. Eli Lilly & Co.,
598 F.3d 1336, 1351 (Fed. Cir. 2010) (en bane) (citation omitted, alteration
in original). "[T]he test for sufficiency 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."
Id.
Claim 17 requires an "aptamer that selectively binds to a binding
agent-analyte complex." The Examiner finds that the Specification does not
provide written description support for the claimed aptamer because "[t]here
is no partial structure or other identifying characteristics disclosed, common
to the members of the genus of aptamers having sufficiently high binding
affinity, that would allow one skilled in the art to envision that Appellant has
truly invented the genus." Ans. 16.
We agree with the Examiner that the Specification does not support
the claimed genus of aptamers. We address Appellant's arguments below.
Appellant argues that the Specification provides support for the
claimed aptamer because "evolving an aptamer as claimed was
straightforward for a person of ordinary skill in the art given the state of
aptamer technology in 2011." App. Br. 11-12. Appellant acknowledges
that it may have been difficult to evolve aptamers against small molecule
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analytes, but contends that the claimed kit solves this problem by
"convert[ing] a small target (small molecule analyte) to a larger target (small
molecule analyte-binding agent complex) and us[ing] an aptamer evolved
against that target in the non-competitive assay." Id. at 10; see also FFl 1.
We are not persuaded.
As an initial matter, the evidence of record does not support that it
would have been straightforward for a person of ordinary skill to evolve
aptamers within the full scope of the claimed aptamer genus. Claim 17
encompasses binding agent-analyte complexes of any size. See FF7-9
( defining relevant terms). Because the claims impose no restriction on the
size of the binding agent, the analyte, or the binding agent-analyte complex,
claim 17 encompasses assays in which both the analyte and the binding
agent are small molecules. As a result, the binding agent-analyte complex
could be a small molecule. The current record suggests that the ability to
evolve suitable aptamers against such a small molecule is "elusive." FF 10
("aptamers ( employed alone) have been shown to recognize small
molecules, however, in general, the binding affinity is poor and ability to
evolve aptamers against all small molecules targets of interest has proved
elusive"); see also, FF3.
Even if it were straightforward to evolve aptamers within the full
scope of claim 17, written description requires more than "a mere wish or
plan for obtaining the claimed ... invention." University of Rochester v.
G.D. Searle & Co., Inc., 358 F.3d 916, 927 (Fed. Cir. 2004) (quoting
Regents of the University of California v. Eli Lilly & Co., 119 F.3d 1559,
1566 (Fed. Cir. 1997)). While the Specification describes methods that can
be used to make aptamers (FF5, FF6, FF12, and FF13; see also, generally,
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Spec. 22-24), that alone is not sufficient. The Federal Circuit addressed an
analogous situation in Rochester, finding that disclosure of "assays for
screening compounds, including peptides, polynucleotides, and small
organic molecules to identify those that inhibit the expression or activity of
the PGHS-2 gene product," did not satisfy the written description
requirement for claims requiring administration of a "compound that
selectively inhibits PGHS-2." Rochester, 119 F.3d at 918, 927; see also
Ariad Pharmaceuticals, Inc., v. Eli Lilly and Company, 598 F.3d 1336, 1344
(Fed. Cir. 2010) (recognizing distinction between requirements for written
description and enablement).
While the Federal Circuit has recognized that "the written description
requirement can in some cases be satisfied by functional description," it has
made clear that "such functional description can be sufficient only if there is
also a structure-function relationship known to those of ordinary skill in the
art." In re Wallach, 378 F.3d 1330, 1335 (Fed. Cir. 2004); Enzo Biochem,
Inc. v. Gen-Probe, Inc., 323 F.3d 956, 964 (Fed. Cir. 2002). Here, the
Specification does not exemplify any aptamers that fall within the genus of
claimed aptamers or identify any structure common to the members of the
genus that would correlate with the claimed function of selectively binding
to the "binding agent-analyte complex." FFl, FF2. Accordingly, we affirm
the Examiner's rejection of claim 17 for failure to comply with the written
description requirement. Because they were not argued separately, claims
18-20 fall with claim 17.
Claim 21 depends from claim 18 and further specifies that "the
binding agent is an antibody." Appellants argue claim 21 under a separate
heading, but rely only on arguments presented with respect to claims 17-20.
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App. Br. 12. Moreover, the additional claim limitation of claim 21 with
respect to the binding agent does not affect our analysis with respect to the
absence of support in the Specification for the claimed genus of aptamers.
Accordingly, we affirm the Examiner's rejection of claim 21 for failure to
comply with the written description requirement.
INDEFINITENESS
Claim 21 depends from claim 18 and further requires that "the binding
agent is an antibody." The Examiner rejected claim 21 as indefinite because
the term "the binding agent" has two possible antecedent bases. It could
refer back to "a binding agent immobilized in or on the membrane strip" as
recited in claim 18 ( which depends from claim 1 7) or it could refer back to
"a binding agent-analyte complex" as recited in claim 17. See Ans. 16-17. 8
We agree with the Examiner that it is not clear to which antecedent "binding
agent" "the binding agent" of claim 21 refers. Accordingly, we affirm the
Examiner's rejection of claim 21 as indefinite.
OBVIOUSNESS OVER PULLI, KONDOU, FITZPATRICK, AND
SCHULTZ
Appellants argue claim 1 7-19 and 21 together. We designate claim
17 as representative. Pulli discloses an immunoassay for small analytes.
FF14. In Pulli's assay, as in the claimed assay, a first binding partner binds
to the analyte and a second binding partner binds to the complex formed
between the first binding partner and the analyte. Id. The Examiner found
that Pulli discloses most of the elements of claim 17, but acknowledged that
8 The Examiner recognizes the possibility that the "binding agent" of claim
1 7 and 18 could be the same and suggests that claim 18 could be amended to
clarify this issue. Ans. 17.
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Pulli does not expressly state that the second binding partner may be an
aptamer. Final Act. 7.
Schultz teaches that DNA aptamers can be used as binding agents in
lateral flow devices in the same manner as antibodies and can bind "virtually
any chemical compound." FF15, FF16. In finding the claimed kit obvious,
the Examiner found that "[i]t would have been obvious to substitute a DNA
aptamer for the second antibody of Pulli et al. (i.e. the capture
antibody/complex-specific antibody) in order to achieve the same purpose,
namely to provide a binding agent to bind to the complex of first antibody
with analyte." Final Act. 10. The Examiner reasoned that the person of
ordinary skill in the art "would be motivated to do this because of the art-
recognized suitability of aptamers for the same purpose as antibodies." Id.
The Examiner concluded that the ordinarily skilled artisan would "have
reasonably expected success in using aptamers that bind to complexes of an
analyte with a first antibody because Schultz et al. teaches that aptamers can
be generated that specifically bind virtually any chemical compound/any
desired target molecule (page 35, lines 20-31 )." Id.
We agree with the Examiner that the kit of claim 1 7 would have been
obvious over the cited art. We address Appellant's arguments below.
Appellant argues that modifying Pulli to use an aptamer would change
the principle of operation in Pulli' s assay because Pulli' s second binding
partner is expressly described to be "proteins, such as antibodies including
antibody fragments." Appellant contends that "[o]ne of ordinary skill in
the art would not characterize aptamers as proteins such as antibodies or
antibody fragments." Reply Br. 9. We are not persuaded.
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Although Appellant argues that the person of ordinary skill would
understand the term "aptamer" to exclude antibody fragments, Appellant
does not identify evidence to support this argument. See Johnston v. IVAC
Corp., 885 F.2d 1574, 1581 (Fed. Cir. 1989) ("Attorneys' argument is no
substitute for evidence."); In re Pearson, 494 F.2d 1399, 1405 (CCPA
1974). There is nothing in the language of claim 17 that would exclude an
antibody fragment from meeting the requirement for an "aptamer that
selectively binds to a binding agent-analyte complex." Nor is there anything
in the Specification that suggests that the term "aptamer" should be
construed to exclude antibody fragments. To the contrary, the Specification
expressly defines "aptamer" as including peptide molecules that bind a
target molecule. FF4. Accordingly, we see no conflict between Pulli's
teaching to use antibody fragments and the Examiner's suggestion to use
aptamers.
Even if the term "aptamer" were construed to exclude antibody
fragments, Schultz teaches that DNA aptamers can be used in place of
antibodies (FF 16) and discloses that aptamers can form "specific binding
pairs with virtually any chemical compound whether monomeric or
polymeric." FF15. Thus, we agree with the Examiner that it would have
been obvious to modify the assay of Pulli to use an aptamer because
aptamers are taught to be useful for the same purpose as antibodies. Id.
Appellant argues that the skilled artisan would not have expected
success in replacing the antibodies used in Pulli with an aptamer. Reply Br.
12-13. We are not persuaded because, as discussed above, Schultz teaches
that DNA aptamers can be used in place of antibodies.
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Appellant argues that Schultz does not support the Examiner's
conclusion that DNA aptamers can be used as binding agents in the same
manner as antibodies. App. Br. 19. Appellant contends that "[t]he
disclosure in Schultz is specific to using aptamers that bind to the analyte,
not an analyte-binding agent complex, i.e., the aptamer would be evolved
against the analyte, not the analyte-binding agent complex, based on the
disclosure in Schultz." Id. at 21. We are not persuaded because, as
discussed above, Schultz teaches that aptamers can form "specific binding
pairs with virtually any chemical compound, whether monomeric or
polymeric." FF15.
Appellant cites McKeague9 as evidence that, because of their low
binding affinities, it was thought that aptamers for small molecules would
"not be clinically useful in a non-competitive binding assay" like that
claimed. App. Br. 19. Appellant also cites to Trumpie 10 as evidence that
"when the analyte is of low molecular mass and has only one epitope, i.e. a
hapten, the format is restricted to the competitive design." Id. From this,
Appellant argues that "[t]he prior art makes clear that using aptamers in a
non-competitive assay to identity small molecules is not obvious, merely
because the technology of evolving aptamers is known." Id. at 18. We are
not persuaded.
9 McKeague, et al., Challenges and Opportunities for Small Molecule
Aptamer Development, 2012 J. NucL. Acrns, Article ID 748913, 1-20
(2012) ("McKeague").
10 Posthuma-Trumpie, et al., Lateral Flow (Immuno)assay: Its Strengths,
Weaknesses, Opportunities and Threats. A literature survey. 393 ANAL
BIOANAL CHEM, 569-582 (2009) ("Trumpie").
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As the Examiner explains, Appellant's argument is not grounded in
the basis of the rejection.
[T]he rejection does not contend that it would have been
obvious to use small molecule-binding aptamers, but rather
complex-directed aptamers. As Appellant notes, Table 2 shows
binding affinities for small molecule aptamers, but this is not
the proposed modification. Pulli teaches the concept of raising
binding partners to complexes involving the analyte and not to
the analyte alone. Accordingly, even if it were established that
one skilled in the art would not expect success in producing
aptamers against small analytes, this is not the proposed
modification.
Ans. 20.
Accordingly, we affirm the Examiner's rejection of claim 17 as
obvious. Because they were not argued separately, claims 18, 19, and 21 fall
with claim 1 7.
OBVIOUSNESS OVER PULLI, KONDOU, FITZPATRICK, SCHULTZ
AND WANG
The Examiner rejected claim 20 over the combination of Pulli,
Kondou, Fitzpatrick, Schultz, and Wang. The Examiner separately rejected
claims 17-21 over the same combination of art. Appellant does not present
any different arguments with respect to these rejections, arguing only that
they should be reversed for the reasons discussed in connection with the
obviousness rejection over the combination of Pulli, Kondou, Fitzpatrick and
Schultz. App. Br. 23-25. Accordingly, we affirm these rejections for the
reasons discussed above.
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SUMMARY
In summary, we affirm the Examiner's rejection of claims 17-21
under 35 U.S.C. § 112 for failure to comply with the written description
requirement.
We affirm the Examiner's rejection of claim 21 under 35 U.S.C. § 112
as indefinite.
We affirm the Examiner's rejection of claims 17-19 and 21 under
35 U.S.C. § 103(a) as obvious over the combination of Pulli, Kondou,
Fitzpatrick and Schultz.
We affirm the Examiner's rejection of claim 20 under 35 U.S.C.
§ 103(a) as obvious over the combination of Pulli, Kondou, Fitzpatrick,
Schultz, and Wang.
We affirm the Examiner's rejection of claims 17-21 under 35 U.S.C.
§ 103(a) as obvious over the combination of Pulli, Kondou, Fitzpatrick,
Schultz, and Wang.
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)(l )(iv).
AFFIRMED
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