Ex Parte Gonzalez-Sapienza et al

Patent Trial and Appeal Board

Mar 20, 2017

12097235 (P.T.A.B. Mar. 20, 2017)

United States Patent and Trademark Office
UNITED STATES DEPARTMENT OF COMMERCE
United States Patent and Trademark Office
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Alexandria, Virginia 22313-1450
www.uspto.gov
APPLICATION NO. FILING DATE FIRST NAMED INVENTOR ATTORNEY DOCKET NO. CONFIRMATION NO.
12/097,235 06/12/2008 Gualberto Gonzalez-Sapienza 76916-166610US-719172 9055
20350 7590 03/22/2017
KILPATRICK TOWNSEND & STOCKTON LLP
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EXAMINER
COUNTS, GARY W
ART UNIT PAPER NUMBER
1678
NOTIFICATION DATE DELIVERY MODE
03/22/2017 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
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PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
BEFORE THE PATENT TRIAL AND APPEAL BOARD
Ex parte GUALBERTO GONZALEZ- SAPIENZ A,
BRUCE HAMMOCK, ANDRES GONZALEZ-TECHERA,
LUCIA VANRELL, and
HEE JOO KIM,1
Appeal 2016-001220
Application 12/097,235
Technology Center 1600
Before ELIZABETH A. LAVIER, RACHEL H. TOWNSEND, and
DEVON ZASTROW NEWMAN, Administrative Patent Judges.
TOWNSEND, Administrative Patent Judge.
DECISION ON APPEAL
This is an appeal under 35 U.S.C. § 134 involving claims to a method
of detecting an analyte, which have been rejected as obvious, as being
indefinite, and for containing new matter. We have jurisdiction under 35
U.S.C. § 6(b).
We affirm-in-part and enter a new ground of rejection pursuant to our
authority under 37 C.F.R. § 41.50(b).
1 Appellants identify the Real Party in Interest as the Regents of the
University of California. (Br. 3.)
Appeal 2016-001220
Application 12/097,235
STATEMENT OF THE CASE
Immunoassays are a simple, fast, and specific tool for analysis of
biological substances. (Spec. 13.) Competitive-format assays are less
precise, sensitive, and fast compared to noncompetive formats. (Id.)
However, “[f]or the detection of small molecules, a sandwich type
noncompetitive ELISA[, enzyme-linked immunosorbent assay,] format is
not applicable because once antibody binds to the target molecule, there is
no site available for the direct binding of secondary reporter antibody.” (Id.
at 14.) The claimed invention is directed to a noncompetitive immunoassay
for detecting small molecules.
Claims 1, 4—9, and 25 are on appeal. Claims 1 and 25 are
representative and read as follows:
1. A method for detecting an analyte, said method comprising:
(a) contacting a sample suspected of containing said analyte
with a first antibody that specifically binds to the analyte,
thereby forming an antibody-analyte complex;
(b) contacting the antibody-analyte complex with an affinity
agent comprising a phage protein fused to a heterologous
polypeptide, wherein the heterologous polypeptide specifically
binds to the analyte of the antibody-analyte complex, thereby
forming an antibody-analyte-affmity agent complex; and
(c) detecting the antibody-analyte-affmity agent complex,
thereby detecting the analyte, wherein the analyte has a
molecular weight of less than about 1360 Da.
25. The method of claim 1, wherein the heterologous peptide
specifically binds to both the analyte and the antibody of the
antibody-analyte complex.
(Br. 25-26.)
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Application 12/097,235
The following grounds of rejection by the Examiner are before us on
review:
1. Claim 25 under 35 U.S.C. § 112, first paragraph, as failing to
comply with the written description requirement.
2. Claim 25 under 35 U.S.C. § 112, second paragraph, as being
indefinite.
3. Claim 1 under 35 U.S.C. § 103(a) as unpatentable over
Monforte2 and Grassi.3
4. Claim 4 under 35 U.S.C. § 103(a) as unpatentable over
Monforte, Grassi, and Thompson.4
5. Claims 5 and 6 under 35 U.S.C. § 103(a) as unpatentable over
Monforte, Grassi, and Kay.5
6. Claims 7—9 under 35 U.S.C. § 103(a) as unpatentable over
Monforte, Grassi, Kay, and McCafferty.6
7. Claim 25 under 35 U.S.C. § 103(a) as unpatentable over
Monforte, Grassi, and Self.7
2 Joseph A. Monforte, WO 02/48403 A2, published June 20, 2002.
3 Jacques Grassi et al., Two different approaches for developing
immunometric assays of haptens, 42 (9) Clin. Chem., 1532—1536 (1996).
4 Thompson et al., US 4,731,326, issued Mar. 15, 1988.
5 Kay et al., US 5,498,538, issued Mar. 12, 1996.
6 McCafferty et al., US 6,806,079 Bl, issued Oct. 19, 2004
7 Colin H. Self et al., High-Performance Assays of Small Molecules:
Enhanced Sensitivity, Rapidity, and Convenience Demonstrated with a
Noncompetitive Immunometric Anti-Immune Complex Assay System for
Digoxin, 40 (11) Clin. Chem., 2035-2041 (1994).
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Application 12/097,235
DISCUSSION
New Matter
The Examiner finds that the language in claim 25 “wherein the
heterologous peptide specifically binds to both the analyte and the antibody
of the antibody-analyte complex” (emphasis added) “was not described in
the specification in such a way as to reasonably convey to one skilled in the
relevant art that the inventor(s), at the time the application was filed, had
possession of the claimed invention.” (Non-Final Action 7.)8 According to
the Examiner, while the Specification at paragraphs 6, 23, 30, and 39
describe a heterologous polypeptide specifically binds to the antibody-
analyte complex, “[tjhere is no description in the specification disclosing the
heterologous peptide specifically binds to both the analyte and the antibody
of the antibody-analyte complex.” (Id.)
We disagree with the Examiner’s conclusion.
Appellants’ Specification provides the following definition for the
term peptide: “The terms ‘polypeptide,’ ‘peptide’ and ‘protein’ are used
interchangeably herein to refer to a polymer of amino acid residues.” (Spec.
142.) Furthermore, the Specification explains that an “[ajntibody” is a type
of polypeptide, i.e., a “polypeptide encoded by an immunoglobulin gene or
fragments thereof that specifically binds and recognizes an antigen.” (Spec.
134.)
The Specification states that the phrase “specifically [ ] binds” when
referring to an antibody “refers to a binding reaction that is determinative of
Office Action mailed March 3, 2014.
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Application 12/097,235
the presence of the antibody’s binding target (e.g., a small molecule, protein
epitope, or a phage protein) in a heterogeneous population of analytes (e.g.,
small molecules, phage proteins, and other biologies).” (Spec. 138.)
Paragraph 6 of Appellants’ Specification states that once the antibody-
small molecule complex is formed by contacting a sample suspected of
containing the small molecule “with an antibody that specifically binds to
the [small] molecule,” the complex is contacted with the affinity agent
comprising a phage protein fused to a heterologous polypeptide “that
specifically binds to the antibody-small molecule complex.”
Figure 1 depicts the foregoing specific binding of antibody to small
molecule and heterologous polypeptide to antibody-small molecule complex
as follows:
(Fig. 1.) As can be seen from the figure, the “peptide” is shown to be in
contact with both the analyte and the antibody to which the analyte is
specifically bound. Thus, this figure depicts “specific binding” to the
analyte and antibody of the analyte-antibody complex. Thus, we agree with
Appellants (Br. 17—18), that the Specification and figures provide sufficient
detail from which one of skill in the art could reasonably conclude that the
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inventor was in possession of the invention recited in claim 25.
Consequently, we reverse the Examiner’s rejection of claim 25 under 35
U.S.C. § 112, first paragraph, as failing to comply with the written
description requirement because it contains new matter.
Indefiniteness
The Examiner finds that “[cjlaim 25 appears to contradict claim 1”
because claim 1 requires the polypeptide to specifically bind to the analyte
of the antibody-analyte complex, whereas claim 25 recites that the
polypeptide specifically binds to “both the analyte and the antibody of the
antibody-analyte complex.” (Non-Final Action 8.)
We disagree with the Examiner’s finding that claim 25 contradicts
claim 1 and the Examiner’s conclusion based thereon that claim 25 is
indefinite. In particular, as Appellants explain, claim 25 would only
contradict claim 1 if “specifically binds” is interpreted “as closed-ended
language such that claim 1 . . . reads ‘the heterologous polypeptide
specifically binds to the analyte and only the analyte. ’” (Br. 18—19.) We
agree with Appellants that claim 1 is not so limited. Claim 1 is open-ended,
using the transition phrase “comprising,” and the contacting step recited in
“(b)” does not include any limiting language regarding the specific binding.
Moreover, Appellants’ definition of “specifically binds” provided in the
Specification at paragraph 38 does not limit claim 1 ’s recitation of specific
binding of the heterologous polypeptide to binding that is only to the analyte
of the antibody-analyte complex. While it is certainly the case that specific
binding can be to the antibody alone, the definition simply notes that such
binding is a binding reaction that is determinative of the present of the
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“antibody’s binding target,” and, further describes that the target can be to a
fusion protein rather than individual components of the fusion protein.
(Spec. 138.) We find the claimed analyte-antibody complex is akin to a
“fusion protein” as described in Appellants’ Specification at paragraph 38.
Thus, we agree with Appellants that there is no contradiction between claim
1 and claim 25. Rather, claim 1 broadly encompasses specific binding by an
antibody to the analyte alone or to the antibody-analyte complex.
Consequently, we reverse the Examiner’s rejection of claim 25 under 35
U.S.C. § 112, second paragraph as being indefinite.
Obviousness
Because the Examiner’s obviousness rejection of claims 1 and 4—9
turn on the same issue, we will consider those rejections together. The
Examiner’s obviousness rejection of claim 25 will be addressed separately.
Claims 1 and 4—9
The Examiner finds that Monforte discloses a sandwich assay for
determining an analyte of interest as claimed except for disclosing detection
of analytes that have a molecular weight of less than about 1360 Da. (Non-
Final Action 10—11.) The Examiner finds, however, that Grassi teaches
“two-site immunometric assay (sandwich assays)” using antibodies for
determining analytes that have a molecular weight of less than about 1360
Da. (Non-Final Action 11.) According to the Examiner, it would have been
obvious to use the antibodies taught by Grassi in the assay of Monforte:
because Grassi et al shows that it is known in the art of
sandwich assays to incorporate antibodies into sandwich
formats for the detection of substance P (SP) (1347 Da),
neurokinin [A] (NKA) (1133 Da) or angiotensin II (1048 Da)
and shows that the use of such reagents provide for highly
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sensitive and specific sandwich immunoassays for small
molecules.
(Non-Final Action 11.)
Appellants argue that the Examiner’s rejection is in error because
claim 1 requires “binding of the heterologous polypeptide to the analyte of
the antibody-analyte complex” and in Grassi’s “sandwich assay” the second
antibody that binds to the small molecule analyte does not bind to the
antibody-analyte complex because the analyte is no longer bound as part of
the antigen-antibody complex. (Br. 21.) We agree with Appellants.
While it is true that Grassi teaches a multistep “sandwich” assay
method for detecting small molecules in which an antibody-analyte complex
is formed by specific binding of the analyte to a first antibody, the binding of
the second “detection” antibody depends upon the deconstruction of the
antibody-analyte complex prior to binding. (Grassi 1534.) The assay works
because the analyte is covalently cross-linked to the solid phase antibody to
which it is specifically bound and then the antibody-analyte complex is
“dissociat[ed] and (or) denature[d]” so that the “hapten-antibody complex
releases the hapten epitope (epitope release) from the antibody binding site.”
(Id.) Because the hapten epitope is no longer specifically bound to the solid
phase antibody, but the hapten is still cross-linked to that antibody at a
different site, a labeled version of the same antibody that is attached to a
solid phase is able to specifically bind the hapten for detection. (Id.) In
other words, the antibody-analyte complex that was formed by specific
binding of the antibody to analyte is no longer present for the labeled
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antibody to bind to. Thus, if one were to use the Grassi reagents in the
Monforte process, the labeled antibody would not “bind[] to the analyte of
the antibody-analyte complex” as required by claim 1.
None of the secondary references relied upon by the Examiner with
respect to claims 4—9 remedies this deficiency. When a prima facie case of
obviousness has not been established, the rejection must be reversed. In re
Fine, 837 F.2d 1071, 1075 (Fed. Cir. 1988). In light of the foregoing, we
reverse the Examiner’s rejection of claims 1 and 4—9 as being obvious over
Monforte and Grassi with or without Thompson, and/or Kay, and
McCafferty.
Claim 25
Claim 25 requires the heterologous peptide “specifically binds to both
the analyte and the antibody of the antibody-analyte complex.”
The Examiner finds that Self discloses an immunometric assay for
detection of small molecule analytes such as digoxin (780 Da). (Non-Final
Action 14.) The Examiner finds that the secondary antibodies that Self uses
“bind to both the antigen/antibody complex.” (Id.) According to the
Examiner,
[i]t would have been obvious to one of ordinary skill in
the art at the time the invention was made to incorporate
antibodies such as taught by Self et al into the method and
affinity agent of Monforte for the detection of digoxin because
Self et al shows that it is known in the art of sandwich assays to
incorporate antibodies into sandwich formats for the detection
of digoxin and shows that the use of such reagents provides for
rapid and robust assay of small molecules similar to those
realized for larger molecules.
(Id. at 14—15.)
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We agree with the Examiner that claim 25 would have been obvious
from Monforte and Self. Appellants contend that Self does not describe
binding of a heterologous polypeptide “to the analyte itself.” (Br. 23.) We
disagree. As discussed above in the new matter discussion, in light of
Appellants’ Specification, a heterologous polypeptide can be an antibody.
Moreover, claim 25 requires that the heterologous polypeptide bind to both
the analyte and antibody of the antibody-analyte complex.
Self describes an immunoassay that uses an anti-immune complex
antibody to detect the analyte of interest. (Self 2035.) As Self explains, the
“anti-immune complex assay is based on the interaction of a receptor such as
a primary antibody with its ligand, such that new binding sites, recognizable
by a secondary antibody, are formed.” (Self 2035 (abs.).) The “secondary
(anti-immune complex) antibody is produced that specifically binds primary
anti-hapten antibody that is combined with hapten but does not bind primary
antibody or hapten alone.” (Self 2035.) Thus, we find that Self teaches an
antibody that specifically binds to both the analyte and the antibody of the
antibody-analyte complex as required by claim 25.
Self teaches that this assay for small molecules provides a “high
performance assay” that is simple, rapid, sensitive and precise. (Id.)
Consequently, we agree with the Examiner that the prior art provides a
reason to combine the reagents of Self with Monforte’s process employing
phage displaying a binding component fused to the phage and that there
would have been a reasonable expectation of success at least for the
detection of the small molecule digoxin. For the foregoing reasons,
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Appellants do not persuade us that the Examiner erred in rejecting claim 25
for obviousness over Monforte, Grassi, and Self.
We note that the Examiner does not rely on Grassi for this rejection. (Non-
Final Action 14—15.) In affirming a multiple reference rejection under 35
U.S.C. § 103, the Board may rely on fewer than all of the references relied
on by the Examiner in an obviousness rationale without designating it as a
new ground of rejection. In re Bush, 296 F.2d 491, 496 (CCPA 1961).
New Ground of Rejection
Claim 1 is rejected as unpatentable under 35 U.S.C. § 103 as obvious
over Monforte and Self.
We adopt the factual findings by the Examiner with respect to
Monforte and Self. (Non-Final Action 10-11, 14—15.) As discussed above,
with regard to the Examiner’s indefmiteness rejection of claim 25 (which we
reverse), claim 1 broadly encompasses specific binding by an antibody to the
analyte alone or to the antibody-analyte complex. Claim 25 specifically
requires the binding be to the antibody-analyte complex. The test of
obviousness is “whether the teachings of the prior art, taken as a whole,
would have made obvious the claimed invention.” In re Gorman, 933 F.2d
982, 986 (Fed. Cir. 1991). For the same reasons the Examiner found claim
25 obvious from the teachings of Monforte and Self, which we affirm above,
we find claim 1 is also obvious. In particular, as the Examiner noted,
It would have been obvious to one of ordinary skill in the art at
the time the invention was made to incorporate antibodies such
as taught by Self et al into the method and affinity agent of
Monforte for the detection of digoxin because Self et al shows
that it is known in the art of sandwich assays to incorporate
antibodies into sandwich formats for the detection of digoxin
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Application 12/097,235
and shows that the use of such reagents provides for rapid and
robust assay of small molecules similar to those realized for
larger molecules. Thus, one of ordinary skill in the art would
have a reasonable expectation of success incorporating
antibodies such as taught by Self [et] al into the method and
affinity agent of Monforte for the detection of digoxin.
(Non-Final Action 14—15.)
We have applied the new rejection only to independent claim 1 and
leave it to the Examiner to determine, in any future prosecution, whether the
rejection should be applied to any of claims 4—9. See MPEP § 1213.02
(“[Sjince the exercise of authority under 37 CFR 41.50(b) is discretionary,
no inference should be drawn from a failure to exercise that discretion.”).
SUMMARY
We reverse the rejection of claim 25 under 35 U.S.C. § 112, first
paragraph, as failing to comply with the written description requirement.
We reverse the rejection of claim 25 under 35 U.S.C. § 112, second
paragraph, as being indefinite.
We reverse the rejection of claim 1 under 35 U.S.C. § 103 (a) as
unpatentable over Monforte and Grassi.
We reverse the rejection of claim 4 under 35 U.S.C. § 103(a) as
unpatentable over Monforte, Grassi, and Thompson.
We reverse the rejection of claims 5 and 6 under 35 U.S.C. § 103(a)
as unpatentable over Monforte, Grassi, and Kay.
We reverse the rejection of claims 7—9 under 35 U.S.C. § 103(a) as
unpatentable over Monforte, Grassi, Kay, and McCafferty.
We affirm the rejection of claim 25 under 35 U.S.C. § 103(a) as
unpatentable over Monforte, Grassi, and Self.
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We enter a new ground of rejection over claim 1; namely claim 1 is
unpatentable under 35 U.S.C. § 103(a) as being obvious over Monforte and
Self.
TIME PERIOD FOR RESPONSE
This decision contains a new ground of rejection pursuant to 37
C.F.R. § 41.50(b). 37 C.F.R. § 41.50(b) provides “[a] new ground of
rejection pursuant to this paragraph shall not be considered final for judicial
review.”
37 C.F.R. § 41.50(b) also provides that the Appellants, WITHIN
TWO MONTHS FROM THE DATE OF THE DECISION, must exercise
one of the following two options with respect to the new ground of rejection
to avoid termination of the appeal as to the rejected claims:
(1) Reopen prosecution. Submit an appropriate amendment of the
claims so rejected or new Evidence relating to the claims so rejected,
or both, and have the matter reconsidered by the examiner, in which
event the prosecution will be remanded to the examiner. . . .
(2) Request rehearing. Request that the proceeding be reheard under
§ 41.52 by the Board upon the same Record. . . .
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-IN-PART; 37 C.F.R, $ 41.50(b)
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