Ex Parte Britz et al

Patent Trial and Appeal Board

Feb 9, 2016

12328854 (P.T.A.B. Feb. 9, 2016)

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.
12/328,854 12/05/2008 Judth A. Britz 04200010CA 7711
30743 7590 02/10/2016
WHITHAM, CURTIS & CHRISTOFFERSON & COOK, P.C.
11491 SUNSET HILLS ROAD
SUITE 340
RESTON, VA 20190
EXAMINER
BELYAVSKYI, MICHAIL A
ART UNIT PAPER NUMBER
1644
MAIL DATE DELIVERY MODE
02/10/2016 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 JUDITH A. BRITZ,
PETER R. SOTTONG, and RICHARD J. KOWALSKI
__________

Appeal 2013-007034
Application 12/328,854
Technology Center 1600
__________

Before DEMETRA J. MILLS, ERIC B. GRIMES, and
JEFFREY N. FREDMAN, Administrative Patent Judges.

FREDMAN, Administrative Patent Judge.

DECISION ON APPEAL
This is an appeal1 under 35 U.S.C. § 134 involving claims to a method
of monitoring an immune response in a patient receiving one or more
immunosuppressive drugs. The Examiner rejected the claims as directed to
non-statutory subject matter and as non-enabled. We have jurisdiction under
35 U.S.C. § 6(b). We affirm.

1 Appellants identify the Real Party in Interest as Cylex, Inc. (see
App. Br. 2).
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Statement of the Case
Background
The “invention provides methods based on the measurement of
metabolic markers of activation in immune cells as an indicator of the
patient’s immune response. The methods may be used to predict clinical
outcomes and determine treatment courses for patients such as transplant
recipients” (Spec. 1, ll. 13–16).
The Claims
Claims 54 is on appeal. Claim 54 reads as follows:
54. A method of monitoring an immune response in a patient
receiving one or more immunosuppressive drugs, comprising
the steps of:
at first and second time periods, determining a value of
an immune response for said patient which reflects activation of
one of CD3, CD4, CD19, or CD56 lymphocytes in a whole
blood sample stimulated by exposure to a mitogen wherein said
value is measured in terms of adenosine triphosphate (ATP)
present in cell lysate of said one of CD3, CD4, CD19 or CD56
lymphocytes isolated from said stimulated blood sample, said
patient receiving said one or more immunosuppressive drugs
between said first and second time periods, said second time
period being one day to one month after said first time period,
wherein said patient is a non-transplant patient that has at
least one of Crohn’s disease, cancer, inflammation, rheumatoid
arthritis, or lupus erythmatosus;
comparing said value determined at said first time period
with said value determined at said second time period, and if
there is a decrease of at least 50 ng/ml ATP, determining that
said patient is at risk of being overmedicated with said one or
more immunosuppressive drugs.

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The Issues
A. The Examiner rejected claim 54 under 35 U.S.C. § 101 as directed
towards non-statutory subject matter (Ans. 3–10).
B. The Examiner rejected claim 54 under 35 U.S.C. § 112, first
paragraph as failing to comply with the enablement requirement (Ans. 10–
19).
A. 35 U.S.C. § 101
The issue with respect to this rejection is: Does the evidence of
record support the Examiner’s conclusion that claim 54 is directed towards
non-statutory subject matter?
Findings of Fact
1. The Specification teaches that the “two major drugs used in
transplant maintenance today are cyclosporine (Novartis) and Tacrolimus I
(Fujisawa). . . . Therapeutic drug monitoring (TDM) for these two
immunosuppressive drugs is routinely performed, as prescribed by the
manufacturers” (Spec. 1, ll. 26–29).
2. The Specification teaches that part of the “Cylex™ Immune
Cell Function Assay5 (ImmuKnow™)” assay involves stimulating the
blood with phytohemagglutinin, followed by “immunoselect[ing] CD4 cells
from both the stimulated and non-stimulated wells.” (Spec. 12, ll. 11–16).
The obtained CD4 cells were lysed, ATP levels measured and the
“concentration of ATP (ng/mL) in each sample was . . . calculated from the
calibration curve using an Excel-based program provided by Cylex™”
(Spec. 12, ll. 15–24; cf. Fig. 1).
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3. Footnote 5 of the Specification referring to the Immuknow™
assay in FF 2 above references “5. Weir, ML Methods for Measurement of
Lymphocyte Function. U.S. Patent #5,773,232:1998” (Spec. 25, ll. 1–2),
demonstrating that the ImmunoKnow™ assay was known as of 1998.

Principles of Law
In Mayo Collaborative Services v. Prometheus
Laboratories, Inc., . . . 132 S.Ct. 1289 . . . (2012), the
Supreme Court set forth a framework for distinguishing
patents that claim laws of nature, natural phenomena, and
abstract ideas from those that claim patent-eligible
applications of those concepts. First, we determine whether
the claims at issue are directed to a patent-ineligible concept.
Id. at 1297. If the answer is yes, then we next consider the
elements of each claim both individually and “as an ordered
combination” to determine whether additional elements
“transform the nature of the claim” into a patent-eligible
application. Id. at 1298. The Supreme Court has described
the second step of this analysis as a search for an “inventive
concept”—i.e., an element or combination of elements that
is “sufficient to ensure that the patent in practice amounts to
significantly more than a patent upon the [ineligible
concept] itself.” Id. at 1294.

Ariosa Diagnostics v. Sequenom, Inc. 788 F.3d 1371, 1375 (Fed. Cir. 2015).
Analysis
We follow the analytical framework set forth by the Supreme Court in
Mayo and applied by our reviewing court in Ariosa. Under this rubric, we
agree with the Examiner that claim 54 sets forth a patent-ineligible law of
nature, specifically, the relationship between immune response as measured
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by ATP levels in particular blood cells and the likelihood that a patient is at
risk for overmedication with an immunosuppressive drug (see Ans. 4).
In Mayo, the claim at issue was directed to
A method of optimizing therapeutic efficacy for
treatment of an immune-mediated gastrointestinal disorder,
comprising:
“(a) administering a drug providing 6-thioguanine to a
subject having said immune-mediated gastrointestinal
disorder; and
“(b) determining the level of 6-thioguanine in said
subject having said immune-mediated gastrointestinal
disorder,
“wherein the level of 6-thioguanine less than about 230
pmol per 8x108 red blood cells indicates a need to increase the
amount of said drug subsequently administered to said subject
and
“wherein the level of 6-thioguanine greater than about 400
pmol per 8x108 red blood cells indicates a need to decrease
the amount of said drug subsequently administered to said
subject.

Mayo Collaborative Services v. Prometheus Laboratories, Inc. 132 S.Ct.
1289, 1295 (2012). In Mayo, the Supreme Court held that this claim was
directed to patent ineligible subject matter, a law of nature. Consistent with
Mayo, “[i]f a law of nature is not patentable, then neither is a process
reciting a law of nature, unless that process has additional features that
provide practical assurance that the process is more than a drafting effort
designed to monopolize the law of nature itself.” Mayo at 1297. In this
case, none of the steps in claim 54 represent more than drafting effort. The
Specification acknowledges that drug monitoring of immunosuppressive
drugs is routine (FF 1) and relies upon a prior art commercially available
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assay for performing the stimulation and measurement steps (FF 2–3). We
therefore agree with the Examiner that there is no principled distinction
between the instant claim 54 and the claim at issue in Mayo (cf. Ans. 4).
Appellants contend that:
In sharp contrast to Mayo, the “hand of man” is clearly
present in the claimed invention. In particular, the claim
requires that a whole blood sample be taken at multiple time
periods (not just once), and that the whole blood sample be
stimulated by exposure to mitogens (this, of course does not
happen in the body, but requires exposing the sample to
some foreign agent that is not present naturally in the whole
blood sample), isolating specific lymphocytes from the
whole blood sample (the isolated lymphocytes are not found
in nature in an isolated form[)].

(Br. 12).
We do not find these arguments persuasive because the two elements
identified as the “hand of man” both represent routine elements taught in the
prior art. Taking blood samples at multiple time periods is routine, as
evidenced by the Specification’s teaching that “drug monitoring (TDM) for
these two immunosuppressive drugs is routinely performed” (FF 1). The
ordinary artisan would recognize that monitoring must be performed more
than one time, as the risk of overmedication continues as long as the drug is
administered to the patient.
Stimulation of the blood with mitogens is part of the prior art
ImmuKnow™ assay (FF 2–3), and was not an inventive contribution of
Appellants. Appellants do not, and cannot, claim the prior art ImmuKnow™
assay that operates by stimulating blood with mitogens, isolating the desired
lymphocytes and measuring ATP levels (FF 2–3). At best, Appellants have
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identified a new relationship in patients taking immunosuppressive drugs
using the prior art ImmuKnow™ assay.
Appellants contend that the “claimed invention requires process steps
which do not occur in nature, and requires those steps to be performed at
different specified times in order to provide information which can be acted
upon, information that would not exist but for the invention” (Br. 13).
We find this argument unpersuasive because the claim in Mayo also
required process steps not occurring in nature, the measurement of 6-
thioguanine levels, and also was performed at particular times, after the
administration of a drug providing 6-thioguanine. Mayo at 1295. Mayo
teaches that “the claims inform 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.” Mayo at 1298.
The same situation obtains here, where all of the additional steps of timing
the blood draw and performing the ImmuKnow™ assay represent routine,
conventional activities (FF 1–2) and the only novelty, if any, involves
informing a physician of data correlating particular levels of ImmuKnow™
assay test results with risk of overmedication of patients.
Conclusion of Law
The evidence of record supports the Examiner’s conclusion that claim
54 is directed towards non-statutory subject matter.
B. 35 U.S.C. § 112, first paragraph
The Examiner finds that “the claim is lacking in enablement because
of the still diverse nature of the types of patients who are being treated with
at least one immunosuppressive drug” (Ans. 10). The Examiner finds that
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“[o]ne has no idea what particular immunosuppressive drug, administered at
what dosage, for the treatment of what condition may have been under
consideration when applicant contemplated this teaching” (Ans. 11). The
Examiner concludes that:
there would be an undue amount of experimentation
required, and there could be a false sense of patient well-
being realized by a physician who decided to just willy-nilly
employ the “at least about 50 ng/ml ATP” limitation of the
claims as an indication of overmedication, without further
direction as to what the drug is and what the dosage of it
might be.

(Ans. 12).
Appellants contend that “the decline of 50 ng/ml ATP is a viable
measure irrespective of different drugs being used, different dosages of
drugs being used, and different illnesses being treated” (Br. 8). Appellants
contend that “Dr. Kowalski indicates that this is because the invention, as is
explained in the application, provides a measure of immune function which
is independent of the drug or the illness being treated” (Br. 8).
We find that Appellants have the better position. Claim 54 simply
requires performance of the prior art ImmuKnow™ assay on samples from
patients with a variety of different diseases. There is no unpredictability or
experimentation required to perform a known assay using known reagents
on patient samples in known diseases.
Thus, the enablement argument rests solely on the question of whether
undue experimentation is required for the correlation that a decrease of 50
ng/ml ATP places a patient “at risk of being overmedicated” as required by
claim 54. Claim 54 does not state that the 50 ng/ml ATP decrease is
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“diagnostic” of overmedication or establishes that a patient is
overmedicated, but rather indicates the possibility of a risk of
overmedication. That ATP decreases are associated with reduced immune
function is supported by the Specification and the Kowalski Declaration.2
Figure 2 of the Specification, reproduced below

illustrates the association of reduced ATP levels with reduced immune
function, showing that healthy people have higher average ATP levels as
compared to transplant patients or as compared to patients with HIV. The
Kowalski Declaration states that “based on research conducted with the
ImmuKnow product . . . a decrease of 50 ng/mL of ATP between two
successive measures taken on at least two different days reflects a significant
decrease of immune function. This decrease of immune function may be
attributed to overmedication” (Kowalski Dec. 4).
Therefore, given the evidence that reduction in ATP levels is
associated with reductions in immune function and that the prior art
ImmuKnow™ assay determines reduced ATP levels lymphocytes obtained

2 Declaration of Dr. Richard Kowalski, dated Feb. 23, 2012.
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from a variety of patients, we conclude that undue experimentation would
not have been required to perform the method of claim 54.
SUMMARY
In summary, we affirm the rejection of claim 54 under 35 U.S.C.
§ 101 as directed towards non-statutory subject matter.
We reverse the rejection of claim 54 under 35 U.S.C. § 112,
first paragraph as failing to comply with the enablement
requirement.

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