Ex Parte McIntyre

Patent Trial and Appeal Board

Jun 22, 2015

11108826 (P.T.A.B. Jun. 22, 2015)

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.
11/108,826 04/19/2005 John A. McIntyre 20415-135719 8819
42798 7590 06/22/2015
FITCH, EVEN, TABIN & FLANNERY, LLP
120 South LaSalle Street, Suite 1600
Chicago, IL 60603-3406
EXAMINER
KOLKER, DANIEL E
ART UNIT PAPER NUMBER
1644
MAIL DATE DELIVERY MODE
06/22/2015 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 JOHN A. MCINTYRE1
____________________

Appeal 2012-011288
Application 11/108,826
Technology Center 1600
____________________

Before ULRIKE W. JENKS, ROBERT A. POLLOCK, and
JACQUELINE T. HARLOW, Administrative Patent Judges.

HARLOW, Administrative Patent Judge.

DECISION ON APPEAL
This is an appeal under 35 U.S.C. § 134(a) involving claims to a
method of altering the binding specificity of proteins by oxidation-reduction
reactions. We have jurisdiction under 35 U.S.C. § 6(b).
We affirm.

1 According to Appellant, the Real Party in Interest is Redox-Reactive
Reagents LLC (App. Br. 1).
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STATEMENT OF THE CASE
“[B]lood from normal individuals [] contains a significant number of
autoantibodies, in a wide variety of types and specificities” (Spec. at 2). The
Specification discloses a method for obtaining autoantibodies “from
biological fluids such as blood from a normal subject by exposing the
biological fluid to an oxidizing agent or to a DC electric current, and that
process is reversible” (Spec. at 3).
The Specification states that “[i]f an oxidizing agent is used to carry
out the method of the invention, the oxidizing agent can be any compound
that is capable of altering the redox state of a biological molecule” (Spec. at
19). “Examples of oxidizing agents include, but are not limited to hemin
and chlorophyll. Other oxidizing agents include potassium permanganate
(KMnO4)” (2/17/2010 Amended Spec. at 2).
Claims 1–10, 17–37, 44, 45, 57, and 58 are on appeal. Claim 1 is
illustrative and reads as follows (emphasis added):
1. A method comprising the steps of providing a
composition comprising at least one protein
suspended or dissolved in a liquid medium, the
protein being selected from the group consisting of
immunoglobulins and antibodies and having a
binding specificity that can be reversibly altered by
a change in its redox state, and exposing the
composition to an oxidizing agent or a DC current
sufficient to reversibly effect the alteration of the
binding specificity of said protein.
Claims 19 and 28, the only other independent claims on appeal, recite
“exposing the composition to an oxidizing agent . . . sufficient to effect the
alteration of the binding specificity of said masked protein” and “exposing
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the biological fluid or extract to an oxidizing agent . . . sufficient to alter a
binding specificity of the autoantibody,” respectively.
Claims 1–10, 17–37, 44, 45, 57, and 58 stand rejected under 35 U.S.C.
§ 112 first paragraph as failing to comply with the enablement requirement.
DISCUSSION
Issue
The Examiner has rejected claims 1–10, 17–37, 44, 45, 57, and 58
under 35 U.S.C. § 112 first paragraph as failing to comply with the
enablement requirement. Three independent claims are on appeal.
However, because each of the independent claims includes a variation of the
claim 1 requirement for an oxidizing agent sufficient to reversibly effect the
alteration of the binding specificity of said protein, and because Appellant
argues the claims together, we focus our discussion on representative claim
1. Claims 2–10, 17–37, 44, 45, 57, and 58 stand or fall with claim 1. 37
C.F.R. § 41.37(c)(1)(vii); see also In re McDaniel, 293 F.3d 1379, 1384
(Fed. Cir. 2002)
The Examiner finds that “Appellant has failed to enable the claimed
invention for the full scope of the genus of oxidizing agents which have been
recited in the claims” (Ans. 5). In particular, the examiner finds that “an
undue amount of experimentation would be required for one to determine
which oxidizing agents are those which would ‘reversibly effect the
alteration of the binding specificity’ [of] an immunoglobulin/antibody
protein, as exemplified by the ‘unmasking’ of autoantibodies” (Ans. 5).
Appellant contends that the Examiner incorrectly interprets the claims
as encompassing the use of “any oxidizing agent,” rather than only those
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oxidizing agents “that are sufficient to alter the binding specificity” of an
immunoglobulin or antibody (App. Br. 5). Appellant further contends that
the Specification provides examples of oxidizing agents sufficient to alter
binding specificity, and that “[o]ne skilled in the art, through routine
experimentation given the guidance in appellant's specification, can
determine which other oxidizing agents are sufficient to do so” (App. Br. 6).
The issue presented is whether the Specification enables the full scope
of the genus of oxidizing agents “sufficient to reversibly effect the alteration
of the binding specificity of said protein” recited in claim 1.
Findings of Fact
FF 1. The Specification discloses that “the oxidizing agent can be any
compound that is capable of altering the redox state of a biological molecule.
More specifically, the oxidizing agent is a molecule that has the ability to be
reduced by acting as an electron acceptor for other molecules that act as
electron donors” (Spec. at 19).
FF 2. The originally filed Specification discloses that “[s]uitable
oxidizing agents include ring compounds that contain a coordinated metal,
particularly an oxidizing metal such as iron. Examples of oxidizing agents
include, but are not limited to hemin and chlorophyll. Other oxidizing
agents such as sodium periodate (NaIO4) or potassium permanganate
(KMnO4).” (Spec. at 19). On February 17, 2010, the Specification was
amended to remove reference to “sodium periodate (NaIO4)” (2/17/2010
Amendment).
FF 3. The Specification discloses that “[t]ypically, when an oxidizing
agent is used, a mixture of the biological fluid or extract and the oxidizing
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agent must be incubated for a period of time, typically for about a day or
overnight” (Spec. at 19).
FF 4. The Specification discloses that “[t]he oxidizing agent should
be used at a concentration sufficient enough to alter the binding specificity
of a protein having an alterable binding specificity, but not at a concentration
that might destroy or denature the protein” (Spec. at 19).
FF 5. The Specification discloses that “[i]n the case of autoantibodies,
it has been found that different types of autoantibodies can interact
differently with different antioxidants. For example, for the unmasking of
aPC autoantibodies, the results are very good with KMnO4 and not as good
with hemin.” (Spec. at 19.)
FF 6. The October 14, 2010 Declaration of Dr. McIntyre discloses
that “On January 5th, 2004, my laboratory data book shows that I set up an
experiment using sodium periodate (Frontier Scientific, Ogden Utah)
abbreviated NaIO4” (10/14/2010 McIntyre Decl.). The McIntyre declaration
further discloses that
I compared the NaIO4 results to the results I obtained by using
the identical experimental protocol wherein I substituted the
oxidizing agent, KMnO4. The experimental conditions were
identical, both NaIO4 and the KMnO4 were incubated
overnight, rocking in a 36 degree incubator. My data book
shows tables of the unmasked autoantibodies by using the
KMnO4 as the oxidizer and contains the statement, “NaIO4 does
not oxidize aPL release.”
(10/14/2010 McIntyre Decl. at 2)
FF 7. The October 14, 2010 Declaration of Dr. McIntyre discloses
that “Experiments performed on January 3rd, 2004, showed that 30 mM
concentrations of KMnO4 were inhibitory and no unmasking was observed”
(10/14/2010 McIntyre Decl. at 2). The McIntyre declaration further
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discloses that “Concentrations of hemin over 200uM will inhibit the
unmasking of autoantibodies. In layman's terms, high concentrations of
oxidizing agents will burn up the proteins” (10/14/2010 McIntyre Decl. at 2–
3).
FF 8. The February 2, 2011 Declaration of Dr. Hyslop discloses that
“Periodate [(NaIO4)] oxidation of IgG performed under identical conditions
provided in the Carroll patent did not unmask autoantibody activity”
(2/2/2011 Hyslop Decl. at 4).
FF 9. The June 16, 2011 Declaration of Dr. Hyslop discloses that
“Periodate oxidation of IgG performed under identical conditions provided
in the Carroll patent did not unmask autoantibody activity” (6/16/2011
Hyslop Decl. at 4).
Principles of Law
“The first paragraph of 35 U.S.C. § 112 requires, inter alia, that the
specification of a patent enable any person skilled in the art to which it
pertains to make and use the claimed invention . . . without ‘undue
experimentation.”’ In re Vaeck, 947 F.2d 488, 495 (Fed. Cir. 1991) (citing In
re Wands, 858 F.2d 731, 737 (Fed. Cir. 1988)). Some experimentation, even
a considerable amount, is not “undue” “if it is merely routine, or if the
specification . . . provides a reasonable amount of guidance with respect to
the direction in which the experimentation should proceed.” In re Wands,
858 F.2d at 737. In particular, “sufficient disclosure . . . to teach those of
ordinary skill how to make and how to use the invention . . . means that the
disclosure must adequately guide the art worker to determine, without undue
experimentation, which species among all those encompassed by the
claimed genus possess the disclosed utility.” In re Vaeck, 947 F.2d at 496.
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“Whether undue experimentation is needed is not a single, simple
factual determination, but rather is a conclusion reached by weighing many
factual considerations.” In re Wands, 858 F.2d at 737. Factors to be
considered include: (1) the quantity of experimentation necessary, (2) the
amount of direction or guidance presented, (3) the presence or absence of
working examples, (4) the nature of the invention, (5) the state of the prior
art, (6) the relative skill of those in the art, (7) the predictability or
unpredictability of the art, and (8) the breadth of the claims. Id.
“[T]he PTO bears an initial burden of setting forth a reasonable
explanation as to why it believes that the scope of protection provided by
that claim is not adequately enabled by the description of the invention
provided in the specification of the application.” In re Wright, 999 F.2d
1557, 1561–62 (Fed. Cir. 1993). “If the PTO meets this burden, the burden
then shifts to the applicant to provide suitable proofs indicating that the
specification is indeed enabling.” Id. at 1562.
Analysis
We find that Appellant has not complied with the enablement
requirement set forth in 35 U.S.C. § 112, first paragraph because undue
experimentation would be required to determine which oxidizing agents are
“sufficient to reversibly effect the alteration of the binding specificity of said
protein.” In particular, we find that the following Wands factors support a
determination that undue experimentation would be required: the breadth of
the claims, the state of the prior art, the predictability or unpredictability of
the art, the amount of direction or guidance presented, and the presence or
absence of working examples.
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Appellant argues that no undue experimentation would be required to
practice the claimed invention. First, Appellant asserts that the claims are
not overly broad because they do not encompass all oxidizing agents, but
“only oxidizing agents that are sufficient to alter the binding specificity”
(Reply Br. 2). Second, Appellant argues that the Specification provides
ample guidance for practicing the claimed invention because it sets forth the
“function of the oxidizing agent,” “the general class of molecules able to
perform the function,” and “even a subclass of compounds able to perform
the function” (Reply Br. 3). Appellant asserts that “one skilled in the art,
through routine experimentation, given the guidance in appellant’s
specification” can identify oxidizing agents capable of performing the
claimed function by
choosing compounds that have oxidizing properties and, using
the guidance in appellant's specification, exposing a
composition including at least one protein (e.g.,
immunoglobulin or antibody) suspended or dissolved in a liquid
medium, and determining whether the oxidizing agent
reversibly effects the alteration of the binding specificity of the
at least one protein.
(Reply Br. 4.)
Third, Appellant contends that the Specification includes “numerous
working examples of using a compound such as hemin as an oxidizing
agent,” and further points out “that chlorophyll may be a suitable oxidizing
agent” (Reply Br. 3). Fourth, Appellant argues that
[t]he fact appellant’s specification mentions a compound that
does not work as an oxidizing agent does not make the
disclosure of the function of the oxidizing agent (“altering the
redox state of a biological molecule”), of another general class
of molecules able to perform the function (“a molecule that has
the ability to be reduced by acting as an electron acceptor for
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other molecules that act as electron donors”) and even of a
subclass of compounds able to perform the function (“include
ring compounds that contain a coordinated metal, particularly
an oxidizing metal such as iron”) any less enabling.
(Reply Br. 4.)
We are not persuaded. As an initial matter, we note that Appellant
does not dispute the Examiner’s findings that the state of the prior art is
undeveloped, and that the art is unpredictable (Ans. 7). These unrebutted
findings support a conclusion of non-enablement because they buttress the
Examiner’s determination that the Specification provides inadequate
guidance to enable one skilled in the field to practice the claimed invention.
For example, we agree with the Examiner that Appellant’s disclosure
in the Specification and supporting declarations establishes the
unpredictability of the art. The Specification discloses evidence of only two
species of chemical oxidizing agents within the genus of oxidizing agents
capable of reversibly effecting the alteration of binding efficiency for the
claimed proteins (FF 5–9; Ans. 7). Moreover, despite performing numerous
experiments, Appellant has been unable to identify a single working
embodiment for a third species of oxidizing agent, periodate, disclosed in the
originally filed Specification as usable for performing the claimed method
(FF 2, 6, 8, 9; Ans. 7). Appellant’s subsequent removal of periodate from
the set of exemplary oxidizing agents disclosed in the Specification in
February 2010 serves to underscore the unpredictability of the art and the
lack of enablement of the claimed invention at the time of filing (FF 2).
Turning to Appellant’s arguments, we agree with the Examiner that
the breadth of oxidizing agents encompassed by the claims is limited purely
by function. In particular, claim 1 includes within its reach any oxidizing
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agent “sufficient to reversibly effect the alteration of the binding specificity
of said protein.” Independent claims 19 and 28 similarly limit the claimed
oxidizing agents only by reference to their ability to alter the binding
specificity of a target protein.
Appellant does not appear to dispute this claim interpretation, but
contends instead that the claims are not overly broad because they “do not
encompass those oxidizing agents that are insufficient to alter the binding
specificity” (Reply Br. 2). We are not persuaded. Appellant’s election to
limit claim scope only by reference to oxidizing agent function, combined
with Appellant’s failure to provide a disclosure sufficient to enable one
skilled in the field to identify such oxidizing agents without undue
experimentation renders the claims non-enabled.
Appellant’s argument that the Specification provides ample guidance
for practicing the claimed invention is likewise unpersuasive. Specifically,
we agree with the Examiner that
appellant has merely given a limited number of particular
examples which test for useable oxidizing agents; but appellant
has given no general guidance for selecting which oxidizing
agents should be tested with an expectation of successful results
(e.g. is there a limit in oxidation strength, as set forth the redox
scale/electromotive series, which one cannot exceed without the
agent being “inhibitory”, or in layman’s terms, “burning up” the
antibody protein; is periodate perhaps beyond such a limit?),
and appellant has given no general guidance for selecting what
conditions to use (e.g. agent concentrations, buffers, incubation
times/temperatures).
(Ans. 11–12.) Indeed, the Specification broadly declares that “the oxidizing
agent can be any compound that is capable of altering the redox state of a
biological molecule” (FF 1), and provides minimal guidance regarding
appropriate conditions for performing the claimed method. For example,
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regarding oxidizing agent concentration, the Specification teaches only that
“[t]he oxidizing agent should be used at a concentration sufficient enough to
alter the binding specificity of a protein having an alterable binding
specificity, but not at a concentration that might destroy or denature the
protein” (FF 4). Similarly, regarding incubation times, the Specification
teaches incubation “for a period of time, typically for about a day or
overnight” (FF 3). Appellant’s failure to provide guidance regarding which
oxidizing agents should be tested with an expectation of success, or how
those oxidizing agents should be tested weighs against a finding of
enablement.
Appellant’s third argument, that the Specification includes “numerous
working examples of using a compound such as hemin as an oxidizing
agent,” and further points out “that chlorophyll may be a suitable oxidizing
agent” (Reply Br. 3) is likewise unavailing. Appellant is correct that the
Specification includes numerous embodiments using hemin and KMnO4 as
the claimed oxidizing agent. The Specification does not, however, include
any working examples using oxidizing agents other than hemin and KMnO4.
Accordingly, we agree with the Examiner, and it is undisputed by Appellant,
that the examples in the Specification “merely show that two species of
chemical oxidizing agents recited in the [dependent] claims, namely hemin
and KMnO4, are useable” (Ans. 8).
We are also unpersuaded by Appellant’s fourth argument, that the
original Specification’s disclosure of periodate for use in the claimed
method, a compound Appellant now admits “does not work as an oxidizing
agent” (Reply Br. 4), renders the Specification “any less enabling” (Reply
Br. 4). We agree with the Examiner that “one of skill reading the originally
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filed disclosure would have reasonably considered that the broadest claims
encompass the use of periodate, since periodate was one of a handful of
particular oxidizing agents taught by Appellant at the time of filing,” and
that “Appellant has failed to provide adequate direction as to how one
should use this agent (e.g. the agent concentrations, buffers, incubation
times/temperatures to be used)” (Ans. 10–11). We further agree with the
Examiner that Appellant’s teaching in the originally filed Specification of an
unworkable oxidizing agent as an exemplary oxidizing agent, despite
Appellant’s inability to successfully use that oxidizing agent at (and after)
the time of invention, supports a conclusion of non-enablement (Ans. 8-9).
Conclusion of Law
A preponderance of the evidence of record supports the Examiner’s
conclusion that claim 1 does not satisfy the enablement requirement. Claims
2-10, 17-37, 44, 45, 57, and 58 have not been argued separately and
therefore fall with claim 1. 37 C.F.R. § 41.37(c)(1)(vii).
SUMMARY
We affirm the rejection of claim 1 under 35 U.S.C. § 112 first
paragraph. Claims 2-10, 17-37, 44, 45, 57, and 58 fall with claim 1.
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)(1)(iv).

AFFIRMED
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