Ex Parte Kodadek

Patent Trial and Appeal Board

Oct 26, 2016

11433069 (P.T.A.B. Oct. 26, 2016)

UNITED STA TES p A TENT AND TRADEMARK OFFICE
APPLICATION NO. FILING DATE
111433,069 05/12/2006
108197 7590 10/28/2016
Parker Highlander PLLC
1120 South Capital of Texas Highway
Bldg. 1, Suite 200
Austin, TX 78746
FIRST NAMED INVENTOR
Thomas Kodadek
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.
UTSD:l578US 9065
EXAMINER
GRUN, JAMES LESLIE
ART UNIT PAPER NUMBER
1678
NOTIFICATION DATE DELIVERY MODE
10/28/2016 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 THOMAS KODADEK1
Appeal2015-005364
Application 11,433,069
Technology Center 1600
Before MELANIE L. McCOLLUM, ULRIKE W. JENKS, and
DEVON ZASTROW NEWMAN, Administrative Patent Judges.
NEWMAN, Administrative Patent Judge.
DECISION ON APPEAL
This appeal under 35 U.S.C. § 134 involves claims to a method of
screening an antibody population from an individual suspected of or having
a disease. The Examiner entered final rejections for obviousness,
indefiniteness, lacking sufficient written descriptive support, and as
containing nonstatutory subject matter. 2 We have jurisdiction under 35
U.S.C. § 6(b). We affirm.
1 Appellants identify the Real Party in Interest as the Board of Regents,
University of Texas System, Austin, TX. App. Br. 3.
2 The rejection under 35 U.S.C. § 112, second paragraph, was withdrawn
(see Advisory Action, mailed May 14, 2014).
Appeal2015-005364
Application 11,433,069
STATEMENT OF THE CASE
The Specification discloses:
The present invention provides methods of using synthetic
molecules, i.e., ligands, that bind ligand binding moieties, such
as proteins, nucleic acids, carbohydrates, or non-adherent cells
present in complex biological mixtures, as biomarkers for a
particular physiological state(s). The synthetic molecules may
have not been previously selected to bind ligand binding
moieties, which includes biomarkers present in a sample. In
some cases the identities of ligand binding moieties known
prior to the process. The invention includes methods
comprising: (a) constructing an array of synthetic molecules
having a plurality of structures; (b) contacting said array with a
complex biological mixture obtained from animals or cells that
exhibit a physiological state of interest, resulting in the capture
of certain biological molecules or cells by certain molecules
immobilized on the array; ( c) assessing binding of certain
captured molecules or cells to this array through the use of a
labeled reagent that binds specifically to a given class of
captured molecules or proteins; and ( d) comparison of this
binding pattern with the binding pattern of an appropriate
control sample that does not represent the physiological state of
interest. Aspects of the invention include constructing the array
from synthetic molecules not previously selected to bind any
particular molecule or cell in the sample of interest. In certain
embodiments, the array of synthetic molecules is an array of
peptoids (peptoid-like oligomers) derived from a combinatorial
library. The complex biological mixture can be a serum sample
obtained from an animal or patient with or suspected of having
a disease. Binding of serum antibodies to the array is typically
quantified by subsequent incubation with a fluorescently
labeled secondary antibody. Peptoids that capture antibodies
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Application 11,433,069
enriched in the diseased state are identified by comparison of
the pattern of antibody binding of the two samples to the arrays.
(Spec. ii 9).
The Issues
The following rejections are before us to review:
Claims 1, 2, 6, 14, 22, 24--34, and 66-68 are rejected under 35 U.S.C.
§ 103(a) as being unpatentable over the combined teachings of Francoeur,3
Thompson,4 Charych,5 and Granoff6 (Ans. 13).
Claims 1, 2, 6, 14, 22, 24--34, and 66-68 are rejected under 35 U.S.C.
§ 103(a) as being unpatentable over Robinson,7 Heine,8 Barry,9 and Charych
(Ans. 16).
Claim 68 is rejected under 35 U.S.C. § 112, first paragraph as lacking
written descriptive support for the claimed subject matter (Ans. 4).
3 Ann-Michele Francoeur, U.S. Pat. No. 4,880,750, issued Nov. 14, 1989
("Francoeur").
4 Vicki S. Thompson et al., U.S. Pat. No. 6,989,276 B2, issued Jan. 24, 2006
("Thompson").
5 Deborah Charych et al., US 2002/0055125, published May 9, 2002
("Charych").
6 Dan M. Granoff and Gregory R. Moe, U.S. Pat. No. 6,030,619, issued Feb.
29, 2000 ("Granoff').
7 William H. Robinson et al., US 2003/0003516 Al, published Jan. 2, 2003
("Robinson").
8 Niklas Heine et al., Synthesis and screening of peptoid arrays on cellulose
membranes, 59 Tetrahedron 9919-9930 (2003) ("Heine").
9 Richard Barry et al., US 2002/0055186 Al, published May 9, 2002
("Barry").
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Application 11,433,069
Claims 1, 2, 6, 14, 22, 24--34, and 68 are rejected under 35 U.S.C.
§ 101 as directed to non-statutory subject matter (Ans. 2).
Claims 1 and 68 illustrate the appealed subject matter and reads as
follows:
1. A method of screening an antibody population in a complex
biological sample from a subject suspected of or having a
disease comprising:
(a) providing an array of peptoid ligands having a
plurality of random-structures, wherein said peptoid ligands are
not preselected based on known reactivity to said antibody
population;
(b) contacting said array with the complex biological
sample from the subject comprising an antibody population;
( c) assessing binding of said antibody population to said
array;
( d) comparing the binding in step ( c) with the binding of
a control antibody population to an identical control array, said
control antibody population representing a healthy or diseased
sample, wherein comparing identifies antibodies in the antibody
population in said complex biological sample that are
associated with the disease.
68. The method of claim 1, further comprising
(a) providing a supplementary array comprising at least
one peptoid ligand identified as binding to an antibody in the
complex biological sample, but not binding to an antibody in
the control antibody population;
(b) exposing the supplementary array to a patient sample
potentially containing disease associated antibodies;
( c) detecting any disease associated antibodies bound to
the at least one peptoid ligand on the supplemental array; and
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( d) comparing the binding in step ( c) with the binding of
a second control antibody population to said array, said second
control antibody population representing a healthy or diseased
sample, wherein said comparing step screens the antibody
population in the complex biological sample for the presence or
absence of disease associated antibodies.
App. Br. Claims App'x. 22.
Obviousness over Francoeur, Thompson, Charych, and GranofJ
The issue is: Does the preponderance of evidence of record support
the Examiner's finding that the teachings of the cited references suggest the
method of claim 1?
Findings of Fact
FF 1. Francoeur teaches
The instant invention, termed antibody fingerprinting, presents
a general identification method whereby animate and inanimate
objects can be identified. It is premised on the hithertofore
unrealized discovery that humans, as well as animals generally
have present in their body, a heretofore unknown set of
individual specific, or IS antibodies [(individual-specific
antibodies)]. When an individual's body fluid (or solids)
containing IS antibodies, is screened against a panel (an n-
dimensional array where n is typically 1 or 2), of multiple
antigens (typically greater than 10,000 different antigens),
distinct antigen-antibody complexes are formed. The antigen-
antibody complexes are detected using an appropriate antibody-
binding detector molecule, typically radioactive or enzymes that
give a colored product on reaction with substrate. The antigen-
antibody reactivity profile, or antibody fingerprint, can be used
to identify individual humans or animals.
Francoeur 3:56-4:5.
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Application 11,433,069
FF 2. Francoeur teaches that a "basic immunological method, as
applied to the identification of individuals" includes:
(a) Obtaining an effective concentration of IS antibodies,
preferably, in solution, from an individual's body fluid, such as
urine, plasma, serum, saliva, perspiration, semen, or lung
washings, or from an individual's body solids such as tissue or
feces .....
(b) Reacting the antibody solution obtained in (a) with an
effective panel of antigens where panel refers to an n-
dimensional array of antigens, where n is typically one or two,
to form antigen-antibody complexes. . ..
( c) detecting the antigen-antibody complexes with an
effective amount of an appropriate detector molecule.
The identity of an individual is established by comparing
the resulting antigen-antibody reactivity profile, or antibody
fingerprint, with that of an earlier obtained profile known to be
characteristic of the individual. Similarly, individuals or
inanimate objects, such as blood transfusions or tissues
obtained after an air crash, may be distinguished by comparing
antibody fingerprints obtained from each.
Id. at 7:3-50.
FF 3. Francoeur teaches that in using the antibody fingerprinting
method in humans, the inventors observed
It is apparent that the fingerprints are virtually identical at early
and late times, and are constant over a multiyear period. The
individual whose fingerprints are shown ... became gravely ill
(vasculitis), and his fingerprint is obtained during this condition
. . . . It is apparent that during the illness, the amount of
antibody-antigen complexes was increased and thus the
intensity of the fingerprint was stronger than when he was well.
Minor changes in the fingerprint were detected.
Id. at 12:49-56.
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FF 4. Thompson teaches
An illustrative embodiment of the invention comprises a
method for analyzing biological material including individual-
specific antibodies, comprising: forming an array of multiple
antigens by attaching the multiple antigens to the surface of a
solid support in a preselected pattern such that the locations of
the multiple antigens are known; obtaining a sample of the
biological material and contacting the array with the sample
such that a portion of the individual-specific antibodies
contained in the sample reacts with and binds to antigens in the
array, thereby forming immune complexes; washing the solid
support containing the immune complexes such that antibodies
in the sample that do not react with and bind to the antigens in
the array are removed; and detecting the immune complexes
and determining the locations thereof such that an antibody
profile is obtained.
Thompson 3:37-51.
FF 5. Thompson discloses "[f]ew studies have been conducted on
individuals \'l1ith long=term diseases. Preliminaf'J results, ho\'l1ever, indicate
that, although a few extra bands may appear, the overall pattern remains
intact." Id. at 2:40-43.
FF 6. Charych teaches
[T]he present invention provides peptidomimetic protein-
binding arrays, their manufacture, use, and application. The
protein-binding array elements of the invention include a
peptidomimetic segment, an anchor segment and a linker
segment connecting the peptidomimetic and anchor segment.
The invention contemplates peptidomimetic array element
library synthesis, distribution, and spotting of array elements
onto solid planar substrates, labeling of complex protein
mixtures, and the analysis of differential protein binding to the
array.
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Charych ,-r 8.
FF 7. Charych teaches
A further aspect of the present invention pertains to a method of
performing a differential binding assay. The method involves
labeling proteins in a protein-containing biological sample
solution, contacting an aliquot of the labeled protein-containing
biological sample solution with an array as described herein,
and analyzing the array to determine differential binding of
proteins in the sample to protein-binding agents of the array.
Id. i-f 12.
Principle of Law
An invention is not patentable under 35 U.S.C. § 103 if it is obvious.
KSR Int'! Co. v. Teleflex Inc., 550 U.S. 398, 427 (2007). Under§ 103: the
scope and content of the prior art are to be determined; differences between
the prior art and the claims at issue are to be ascertained; and the level of
ordinary skill in the pertinent art resolved. Against this background, the
obviousness or nonobviousness of the subject matter is determined.
Graham v. John Deere Co., 383 U.S. 1, 17 (1966). A central question in
analyzing obviousness is "whether the improvement is more than the
predictable use of prior art elements according to their established
functions." KSR, 550 U.S. at 417.
Under the proper legal standard, a reference will teach away
when it suggests that the developments flowing from its
disclosures are unlikely to produce the objective of the
applicant's invention. A statement that a particular
combination is not a preferred embodiment does not teach away
absent clear discouragement of that combination.
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Syntex (U.S.A.) LLC v. Apotex, Inc., 407 F.3d 1371, 1380 (Fed. Cir. 2005)
(citations omitted).
Analysis
The Examiner provides sound fact-based reasoning for combining
Francoeur, Thompson, Charych, and Granoff. We adopt and incorporate by
reference the Examiner's findings and conclusions as presented in the Final
Action mailed June 6, 2013 and Answer. We address the arguments raised
by Appellant on appeal below.
Appellant argues that Francoeur's "fingerprint assay is about
identifying antigens, not antibodies" and that the reference does not teach
profiling disease because it teaches antibodies could only be useful in
diagnostics "'on purification."' App. Br. 13. Appellant further argues that
Francoeur does not disclose profiling of disease because Francoeur does not
teach that "the [antigen] pattern changed," rather Francoeur observed only
an increase in the immune complexes as the disease progressed. Id. at 13-
14.
Appellant argues that Charych likewise does not teach using
antibodies to profile disease, but rather teaches use of "other types of
molecules, e.g., cancer or infectious disease proteins." For support
regarding what Charych teaches, Appellant relies on the background section
of Thompson for its disclosures regarding the teachings of Francoeur. Id. at
15. Specifically, Appellant points to Thompson's disclosures, inter alia,
"[a]n individual's [antibody] profile is apparently stable for life and is not
affected by short-term illnesses"' as a teaching away and the further
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statement "[ffew studies have been conducted on individuals with long-
term diseases. Preliminary results, however, indicate that, although a few
extra bands may appear, the overall pattern remains intact" as evidence
that "Francoeur disclosed that antibodies could not be useful as a
'fingerprint' for a disease state," that Thompson "adopted th[is] same view"
by citing Francoeur and Charych "provides no evidence to the contrary." Id.
at 15-16.
Finally, Appellant argues that "making changes to the cited art in
order to arrive at the present invention would run directly contrary to the
clear teachings therein." Id. at 17-18.
We are not persuaded that the Examiner erred in rejecting claim 1
over Francoeur, Thompson, Charych, and Granoff. Francoeur teaches a
blocked fingerprint assay with a "basic immunological method" similar to
that of claim 1. FF 1-2. Appellant's argument that Francoeur teaches
"antigens, not antibodies" is misguided as the antigens taught in Francoeur's
method serve the exact same purpose as the peptoid ligands of the instant
invention: the Francoeur antigens are exposed to and bind to antibodies in
the biological sample to create a profile of the antibodies present in the
tested individual. Id.; Spec. i-f 3: "In particular, the invention relates to
compositions and methods for profiling or fingerprinting proteins in a target
sample, such as antibodies." Charych teaches use of peptoid ligands to
assay antibodies (FF 6-7); without any evidence to the contrary, we agree
with the Examiner that substitution of peptoid ligands for the antigens of
Francoeur is a straightforward process within the ability of one of ordinary
skill in the art, as is antibody purification for diagnostic use. See In re Fout,
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675 F.2d 297, 301(CCPA1982) ("Because both [references] teach a method
for separating caffeine from oil, it would have been prima facie obvious to
substitute one method for the other. Express suggestion to substitute one
equivalent for another need not be present to render such substitution
obvious.").
Appellant's argument that Francoeur and Thompson fail to teach disease
profiling because they do not disclose differences in the "pattern" of the
antibody profile is not persuasive because claim 1 does not recite detecting
an antibody expression "pattern," but rather recites "identif[ication of]
antibodies in the antibody population in said complex biological sample that
are associated with the disease." Thus, the scope of claim 1 is directed at
what Francoeur and Thompson teach: use of arrays to determine the
presence of antibodies. FF 1--4.
Regarding the teaching of disease profiling, Francoeur and Thompson
both disclose that "extra bands" appear in the antibody profiles of samples
taken from individuals with a long-term disease. FF 5. Moreover Francoeur
teaches "the amount of antibody-antigen complexes was increased and thus
the intensity of the fingerprint was stronger" in a patient with vasculitis (FF
3). We are not persuaded that the cited references teach away from
"applying a[] peptoid-antibody profile for the purpose of distinguishing
disease[] from healthy states" (App. Br. 16) because they do not "suggest[]
that the developments flowing from [their] disclosures are unlikely to
produce the objective of the applicant's invention. Syntex, 407 F.3d at 1380.
Accordingly, we affirm the rejection of claim 1 over Francoeur, Thompson,
Charych, and Granoff. Claims 2, 6, 14, 22, 24--34, and 66-68 have not been
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argued separately and therefore fall with claim 1. 37 C.F.R.
§ 41.37(c)(l)(iv).
Obviousness over Robinson, Heine, Barry, and Charych.
The issue is: Does the preponderance of evidence of record support
the Examiner's finding that the teachings of the cited references suggest the
method of claim 1?
Findings of Fact
FF 8. Robinson discloses
For the purposes of the invention, arrays of autoantigens and
autoantigen-derived epitopes can be used to determine a
patient's antibody specificity profile for the identification or
determination of: 1. patients likely to develop disease; 2.
patients likely to develop more or less severe disease; 3.
patients likely to respond to a particular therapy, or to have an
adverse event related to a particular therapy; 4. patient-specific
therapy; and, 5. \'l1hether a particular therapeutic inter1ention
has been successful, unsuccessful, or detrimental. An
autoantigen array comprises the various autoantigens either
known to be associated with disease, suspected to be associated
with a particular disease, or a library of potential autoantigens.
An autoantigen array, in one instance may include autoantigens
optimized for a particular disease, while in another instance
may include a library of unknown antigens to identify targets of
the antibody response in patients with a disease.
Robinson i-f 4 7.
FF 9. Robinson recites in Claim 30:
30. A method for treating autoimmune disease comprising
(a) determining the epitope specificity profile of a patient
comprising the steps of:
(1) preparing an epitope array;
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(2) physically contacting the epitope array from step (1) with a
patient sample comprising antibodies;
(3) identifying the disease associated epitopes within the array
that bind to antibodies within the patient sample from step (2);
( 4) comparing the antibodies bound to the disease associated
epitopes in step (3) with (i) antibodies binding to the disease
associated epitopes within the array of step (1) wherein the
antibodies are known to be associated with the disease; and, (ii)
antibodies binding to the disease associated epitopes within the
array of step (1) wherein the antibodies are not associated with
the disease;;(b) designing a patient specific treatment regimen
based upon the epitope specificity profile of step (a) comprising
the steps of: ( 1) determining the epitopes bound by the
antibodies in the patient sample; and, (2) administering one or
more epitopes to the patient.
Analysis
The Examiner provides sound fact-based reasoning for combining
Robinson, Heine, Barry, and Charych. We address the arguments raised by
Appellant on appeal below.
Appellant argues that the cited references fail to teach the claimed
invention. Appellant argues:
Robinson et al. does not use a random library, but rather, an
array with known immunogenic components having a high
affinity for specific antibodies already associated with a
particular disease. These antigens were selected for their
biological properties and thus are not "random" arrays. In
contrast, the claimed invention uses peptoids with random
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structures that are not known as "antigens" and are not biased to
a particular antibody or a particular disease state.
App. Br. 18-19.
Appellant argues that Robinson's teaching that "[a]n autoantigen
array, in one instance may include autoantigens optimized for a particular
disease, while in another instance may include a library of unknown
antigens to identify targets of the antibody response in patients with a
disease" is a "single passing comment" and because "every single example
offered by this reference deals with the use[] of preselected or biased
libraries - not random libraries ... this document would do nothing to
convince the skilled artisan that random peptoid arrays could or should be
used to distinguish diseased from healthy subjects." Id. at 19-20.
Appellant further argues none of Heine, Barry or Charych supply
teaching on use of a "'random' library" because Heine "uses an isolated and
purified monoclonal antibody," Barry "requires the array to comprise
capture agents (preferably antibodies) that are specific for a target peptide
fragment in a sample," and Charych "shows binding to a known, selected
antibody" Id. at 19-21. Finally, Appellant argues Charych "does not
provide any teaching of screens for unknown antibodies associated with a
disease, and certainly no comparison of healthy and diseased samples except
in the case of labeled (and known) proteins which are screened against the
library." Id. at 20.
We are not persuaded that the Examiner erred in rejecting claim 1
over Robinson, Heine, Barry, and Charych. Robinson teaches that arrays of
autoantigens and autoantigen-derived epitopes can be used to determine a
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patient's antibody specificity profile for the purpose of disease diagnosis and
therapy. FF 8. Robinson discloses that the array may be prepared from
autoantigens that are "known to be associated with disease," "suspected to
be associated with a particular disease" or a "library of potential
autoantigens" (e.g., proteins of yet undetermined reactivity). Id. Robinson
further discloses that the library may include "unknown antigens to identify
targets of the antibody response in patients with a disease." Id. Robinson
claims a method of treating autoimmune disease "wherein the antibodies are
not associated with the disease." FF 9. In light of these specific disclosures,
and without evidence to the contrary, we find Appellant's attorney argument
alone insufficient to overcome the Examiner's strong prima facie case of
obviousness. See In re Geisler, 116 F.3d 1465, 1470 (Fed. Cir. 1997)
(" [A ]ttomey argument [is] not the kind of factual evidence that is required to
rebut a prima facie case of obviousness"). Accordingly, we affirm the
rejection of claim 1 over Robinson, Heine, Barry, and Charych. Claims 2, 6,
14, 22, 24--34, and 66-68 have not been argued separately and therefore fall
with claim 1. 37 C.F.R. § 41.37(c)(l)(iv).
Written Description
The Examiner finds that with respect to claim 68:
The claim is drawn to a method of screening for antibodies
associated with disease that bind to an entirely undefined
identified subpopulation of an entirely undefined random
population of peptoid ligands that do not bind control
antibodies. The invention as claimed encompasses all known
or potential diseases or broad categories of diseases, any
antibody populations, and any genus of peptoid ligands of any
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structure since virtually any antibody or peptoid can be
screened from any patient sample. The specification does not
teach how any particular peptoid ligand structure or antibody
binding thereto is definitively or even predictably associated
with any particular disease. Thus, absent further written
description and guidance from appellant, one would not know
or be able to predict what peptoid ligands specifically bind to
the relevant antibodies, do not bind to control antibodies, and
predictably function as associated in the assay with any
particular disease ... Furthermore, the specification does not
teach how to associate a particular disease with any particular
"fingerprint" of antibody profile because no structure, genus, or
species of peptoid(s) performing the function of binding
relevant antibodies for any particular disease and not binding
control antibodies is disclosed, only numbers of undefined
random peptoids which differ in signal intensity among
individuals or a limited number of individuals are disclosed.
Ans. 4---6.
Appellant responds:
The subject matter here lies in the use of a peptoid array of
sufficient complexity - any peptoid array - to distinguish
diseased from healthy patients. Clearly, appellant has not done
this with specific patterns of specific peptoids and correlated
them with specific disease states. However, the ability of
peptoid arrays to provide this level of discrimination in general
is the subject matter of the invention, and not some particular
set of peptoids for use in diagnosing a particular disease.
App. Br. 8.
Appellant further argues that the differences between claim 68 and claim 1,
which is not rejected, are "inconsequential" because it "merely extends from
step ( d) of claim 1, and puts into play the relevant peptoid( s) bound[] to
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disease-specific antibodies from claim 1 in a second detection. Reply Br. 4--
5. According to Appellant, [n]o particular disease state or peptoid needs to
be identified because the claim is generic to the endeavor of correlating
antibodies and peptoids with diseases." Id. at 5.
We find that the Examiner has the better position. We agree with
Appellant that claim 68 extends from the final step of claim 1, and explains
what next steps could be taken with peptoids that are identified as associated
with disease using the method of claim 1. However, Appellant has not
disclosed any such peptide as required to enable one of skill in the art to
practice the claimed invention in compliance with§ 112. See University of
Rochester v. G.D. Searle & Co., 358 F.3d 916, 926, 69 USPQ2d 1886, 1895
(Fed. Cir. 2004) ([I]t is undisputed that the ... patent does not disclose any
compounds that can be used in its claimed methods. The claimed methods
thus cannot be practiced based on the patent's specification, even
considering the knowledge of one skilled in the art. No compounds that will
perform the claimed method are disclosed, nor has any evidence been shown
that such a compound was known.") Appellant acknowledges that he has
not performed the claimed method "with specific patterns of specific
peptoids and correlated them with specific disease states." App. Br. 8. Such
effort would be necessary in order to claim use of that antibody in the
claimed method. See Noelle v. Lederman, 355 F.3d 1343, 1349 (2004), in
which the Federal Circuit found that "as long as an applicant has disclosed a
'fully characterized antigen,' either by its structure, formula, chemical name,
or physical properties, or by depositing the protein in a public depository,
the applicant can then claim an antibody by its binding affinity to that
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described antigen." Given that Appellant has not undertaken this work, but
the scope of claim 68 includes the fruits of such labor, we affirm the written
description rejection of claim 68.
Nonstatutory Subject Matter
The Examiner finds that
[T]he claimed invention is directed to a non-statutory subject
matter because it is not a patent-eligible practical application of
a law of nature or of a naturally occurring correlation, i.e.[,] of a
natural principle. The claims are directed to a naturally
occurring correlation between a disease and associated levels or
presence of an antibody biomarker profile ... [ w ]hen the claims
are considered as a whole, the steps taken together amount to no
more than recognizing the natural principle itself.
Final Act. 4--5; see Ans. 3--4. The Examiner reached this conclusion by
applying the test set out in Mayo Collaborative Services v. Prometheus
Laboratories. Inc., 132 S. Ct. 1289 (2012).
Appellant argues the claims "provide a particular transformation -
they require use of an array to interrogate a biological sample, during which
both the sample and the array are transformed." App. Br. 5. Appellant
argues the law of nature at issue, "whether a patient has [] antibodies
reflective of a disease state - is quite practically applied in [] step ( d) [of the
method]" and that the claim "provides more than a mere 'concept' as it
solves the problem of diagnosis in a tangible way- antibodies bound to an
array." Id. Appellant further argues the claimed "methods rely on novel,
man-made antigen surrogates (e.g., synthetic ligands/peptoids) that are being
recognized by immune reactivities, i.e., antibodies," and that step (a) "is
'loaded' with man-made features that clearly go beyond any 'law of nature"'
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because the claim requires "a plurality of random structures that are not
preselected based upon a known reactivity to an antibody population." Id. at
5-7. According to Appellant, "[t]he only 'law of nature' present under the
current facts relates to patients that have or do not have a particular disease
that produces potentially detectable antibodies" but the "'end product' of the
claim - a comparison that leads to identification of antibodies f[ or] m a
diseased sample that bind to man-made ligands on an array versus a control
sample [-] does not create a monopoly on a law of nature." Id. at 6-7.
We agree with the Examiner that, under the two-step test of Mayo, the
claims are not directed to patent-eligible subject matter. The !viayo court
applied its test to claims that are similar to those of the instant application.
In lvfayo, the claimed invention was a "method of optimizing therapeutic
efficacy for treatment of an imrnune-mediated gastrointestinal disorder~'
comprising administering a certain class of drug and then detennining the
level of 6-thioguanine ( 6-TG) in a patient, where a level of 6-TG belmv or
above certain amounts indicated a need to increase or decrease, respectively,
the dn1g dosage. A1ayo, 122 S. Ct at 1295.
Claim 1 of the instant application is similar, in that it is directed to a
method of screening an antibody population in a biological sample and
comparing the results to those of a control antibody population to assess
whether antibodies associated with disease are present.
The J\1ayo Court concluded that the claims at issue in that case "set
forth laws of nature--namely, relationships between concentrations of certain
metabolites in the blood and the likelihood that a dosage of a thiopurine drug
wm prove ineffective or cause harm.'' Id. at 1296.
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Application 11,433,069
Similarly here, as acknowledged by Appellant, claim l on appeal sets
forth a law of nature--namely, the relationship between the level of
expression of detectable antibodies that is made by a test subject and
whether that subject has or does not have a disease. App. Br. 6. Under the
first step of the A1ayo test, claim 1 on appeal is directed to a law of nature or
natural phenomenon.
The lviayo Comi next turned to the question "[ w ]hat else is there in
the clairns before usT' ld. at 1297. The claims in A1ayo included an
"'administering"' step, a "'determining'" step, and a "'wherein"' clause. Id.
The Court concluded that "[t]he upshot is that the three steps simply tell
doctors to gather data frmn which they may draw an inference in light of the
correlations.'' Id. at 1298. In other words, the claims 1nfonn a relevant
audience about certain laws of nature; any additional steps consist of well-
understood, routine, conventional activity already engaged in by the
scientific community; and those steps, when viewed as a whole, add nothing
significant beyond the sum of their parts taken separately. Id. The Court
concluded that "the steps are not sufficient to transform unpatentable natural
correlations into patentable applications of those regularities." Id.
Like the steps of the claims in Afayo, the manipulative steps of claim 1
on appeal also "consist of weII-understood, routine, conventional activity
already engaged in by the scientific community.'' Id.
Providing an array of peptoid ligands is known in the art as shown by
Chary ch in il~r 3 3----69, which summarizes methods for making "Protein-
B inding Agent Arrays."
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Appeal2015-005364
Application 11,433,069
Using anays with a plurality of random ligands that are not
preselected based on known reactivity to antibody populations is also
routine, as shown by Thompson in 5:63----9:24) teaching methods for
constn1cting arrays (e.g., 7:36-38 "[t]he antigens, whether selected
randomly or nonrandomly, are disposed on the solid support to result in the
array") as well as methods of assaying the binding of antibodies by
contacting the an-ay with a sample, followed by assessing the binding and
comparing the binding to a control population.
The final step of identifying the screened antigens to identify
antibodies in a biological sample that are associated with a disease is also
routine5 as shown by Robinson ii 71:
The means for identifying the disease-associated antigens
within the array that bind to the antibodies within the patient
sample utilize methods for detection that are known in the art.
Those methods of identification may include pre-labeling the
sample directly or indirectly; adding a second stage antibody
that binds to the antibodies or to an indirect label, e.g. labeled
goat anti-human serum, rat antimouse, and the like. Other
methods of identification include analysis of addressable
elements such as beads, nanoparticles, tags, cleavable tags and
other physical properties of or conferred upon the elements
within the array. Varying concentrations of a single epitope
may be present in order to facilitate quantitation of the bound
antibody.
Robinson i-f 71.
Thus, when claim 1 is considered as an ordered cmnbination, it
infonns a relevant audience of ce1iain laws of nature: specifically,
that the production of antibodies by persons having a disease can be
used to identify those persons as having the disease. Any additional
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Application 11,433,069
steps of claim l consist of we11-understood, routine, convention a]
activity already engaged in by the scientific community as shmvn in
Charych, Thompson, and Robinson.
\Ve conclude that, under the Mayo test, claim 1 is directed to patent
ineligible subject matter. The rejection of claim 1 under 35 U.S.C. § 101 is
affirmed. Claims 2, 6, 14, 22, 14--34, and 68 were not argued separately and
therefore fall with claim 1. 37 C.F.R. § 41.37(c)(l)(iv).
SUMMARY
We affirm the rejection of claims 1, 2, 6, 14, 22, 24--34, and 66-68
under 35 U.S.C. § 103(a) as being unpatentable over the combined teachings
of Francoeur, Thompson, Charych, and Granoff.
We affirm the rejection of claims 1, 2, 6, 14, 22, 24--34, and 66-68
under 35 U.S.C. § 103(a) as being unpatentable over the combined teachings
of Robinson, Heine, Barry, and Charych.
We affirm the rejection of claim 68 under 35 U.S.C. § 112, first
paragraph, as lacking written descriptive support for the claimed subject
matter.
Claims 1, 2, 6, 14, 22, 24--34, and 68 are rejected under 35 U.S.C.
§ 101 as directed to non-statutory subject matter.
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Application 11,433,069
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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