Ex Parte Breton et al

Patent Trial and Appeal Board

Mar 21, 2017

12665149 (P.T.A.B. Mar. 21, 2017)

United States Patent and Trademark Office
UNITED STATES DEPARTMENT OF COMMERCE
United States Patent and Trademark Office
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APPLICATION NO. FILING DATE FIRST NAMED INVENTOR ATTORNEY DOCKET NO. CONFIRMATION NO.
12/665,149 12/17/2009 Marc D. Breton 070239.000020 8824
134006 7590 03/23/2017
Vorys, Sater, Seymour and Pease LLP (UVA)
1909 K St., NW
Ninth Floor
Washington, DC 20006
EXAMINER
RIGGS II, LARRY D
ART UNIT PAPER NUMBER
1631
NOTIFICATION DATE DELIVERY MODE
03/23/2017 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
following e-mail address(es):
vmdeluc a @ vorys. com
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PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
BEFORE THE PATENT TRIAL AND APPEAL BOARD
Ex parte MARC D. BRETON and BORIS P. KOVATCHEV1
Appeal 2014-004270
Application 12/665,149
Technology Center 1600
Before JOHN G. NEW, TAWEN CHANG, and RYAN H. FLAX,
Administrative Patent Judges.
CHANG, Administrative Patent Judge.
DECISION ON APPEAL
This is an appeal under 35 U.S.C. § 134(a) involving claims to
processor-implemented methods of managing diabetes by measuring blood
glucose variability and computing insulin sensitivity, which have been
rejected as obvious. We have jurisdiction under 35 U.S.C. § 6(b).
We REVERSE.
STATEMENT OF THE CASE
“Diabetes is a complex of disorders[] characterized by . . .
hyperglycemia,” i.e., abnormally high blood glucose level. (Spec. 1:21-22.)
1 Appellants identify the Real Party in Interest as University of Virginia
Patent Foundation. (Appeal Br. 1.)
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Application 12/665,149
Thus, “[t]he ability of insulin to stimulate glucose metabolism is of
fundamental importance in the development and clinical course of diabetes.”
(Id. at 2:2-3.)
Insulin sensitivity (SI) refers to “the sensitivity of glucose clearance to
plasma insulin variations.” (Mat 2:9-11, 12-13.) The Specification
explains that SI may be used to calculate a patient’s insulin/carbohydrate
ratio2 and insulin correction factor,3 which are “critical for the optimal
control of diabetes.” (Id. at 11-20.) According to the Specification, SI
“change[s] over time and with various modes of treatment,” and is further
affected by, e.g., the effects of physical activity and natural circadian cycles
(id. at 3:23-30); therefore, “methods and systems for tracking the changes in
insulin sensitivity are needed for the day-to-day optimization of diabetes
control” (id. at 4:3M). Further according to the Specification, because the
“classic methods” of estimating SI require “invasive hospital-based
interventions” that cannot be frequently performed on an individual, “it is
important to find correlates of insulin sensitivity and other metabolic
parameters that can be derived from readily available data collected in a
person’s natural environment, such as self-monitoring blood glucose data
(SMBG).” (Mat 4:4-10.) The Specification states:
An aspect of an embodiment of the present invention is
... the estimate of individual insulin sensitivity (SI) derived
from personal parameters and SMBG data. The computation of
2 The insulin/carbohydrate ratio is the ratio by which the amount of
carbohydrates to be ingested by a person is multiplied to determine “the
amount of insulin . . . needed by a person to compensate for the carbohydrate
content of an incoming meal.” (Spec. 4:11-14.)
3 Insulin correction factor is the factor by which the difference between a
person’s actual and target blood glucose levels is multiplied to arrive at the
amount of insulin needed to reach the target. (Id. at 4:15-18.)
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Application 12/665,149
the two components of an insulin dose calculator, carbohydrate
ratio and correction factor, uses this estimate, which allows the
tailoring of carbohydrate ratio and correction factor to the
present state of the person.
{Id. at 8:25-29.)
Claims 25-21, 31-35, and 39-41 are on appeal.4 Claim 25 is
illustrative and reproduced below:
25. A processor implemented method of measuring blood
glucose variability in a diabetic human, combining blood glucose
variability with a personal score computed from personal
parameters of said diabetic human to compute insulin sensitivity
(SI) of said diabetic human, and applying the SI of said diabetic
human to manage at least one component of diabetes
management of said diabetic human, comprising:
computing, by a processor, an estimate of the diabetic
human’s SI from routine self-monitoring blood glucose (SMBG)
data; and
using said SI to derive said at least one component of said
diabetes management for said diabetic human, selected from the
group consisting of:
a carbohydrate ratio used to estimate the amount of
insulin needed to compensate for an upcoming meal, or
a correction factor used to adjust the insulin amount so
that a target glucose level can be reached, or
both said carbohydrate ratio and said correction factor;
wherein computing an estimate of SI comprises:
processing, by a processor, said SMBG data to determine
blood glucose variability in said diabetic human; and
combining, by a processor, said determined blood glucose
variability with a personal score computed for said diabetic
human from parameters including the diabetic human's age, body
mass index, insulin units per kilogram weight and the duration of
the diabetes in the diabetic human.
4 The Examiner states that “[cjlaims 28-30 and 36-38 are objected to but
would be allowed if written in independent form.” (Ans. 2.)
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Application 12/665,149
(Appeal Br. 12 (Claims App’x).)
The Examiner rejects claims 25, 31-33, and 39-41 under 35 U.S.C.
§ 103(a) as being unpatentable over Ginsberg5 and Ford.6 (Ans. 3.)
The Examiner rejects claims 26, 27, 34, and 35 under 35 U.S.C.
§ 103(a) as being unpatentable over Ginsberg, Ford, and Kovatchev.7 (Id.)
DISCUSSION
Issue
The Examiner has rejected claims 25, 31-33, and 39-41 under 35
U.S.C. § 103(a) as obvious over Ginsberg and Ford and claims 26, 27, 34,
and 35 as obvious over Ginsberg, Ford, and Kovatchev. Because the same
issue is dispositive both rejections, we discuss them together.
The Examiner finds that,
[rjegarding claims 25, 33 and 41, Ginsberg teaches a method
for evaluation of insulin sensitivity (SI) of a user from routine
self-monitoring blood glucose (SMBG) data, comprising
applying the SI to derive at least one component of diabetes
managements, i.e. correction of insulin dose. Ginsberg teaches
an apparatus and computer program product comprising a
processing device programmed with an algorithm(s) for
performing the method, and associated with a sensor for
obtaining blood glucose levels. Ginsberg teaches carbohydrate
to insulin ratios (CIRs) to determine the correct amount of
insulin for a meal. Ginsberg provides a data set of blood
glucose readings, determining a level corresponding to the
difference in glucose readings at different time points in a time
period, suggesting a blood glucose variability, an amount of
insulin administered to the patient during the time period, with
5 Ginsberg, US 2005/0192494 Al, published Sept. 1, 2005.
6 Earl S. Ford, Body Mass Index, Diabetes, and C-Reactive Protein Among
U.S. Adults, 22 Diabetes Care 1971 (1999).
7 Boris P. Kovatchev et al., Evaluation of a New Measure of Blood Glucose
Variability in Diabetes, 29 Diabetes Care 2433 (2006).
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Application 12/665,149
respect to a personal CIR, wherein a CIR is different for each
person, suggesting weight of the person as a factor in
determining a personal CIR, and a value selected from a range
of numbers divided by the daily insulin dose, suggesting a
personal score.
(Ans. 5 (citations omitted).)
The Examiner finds that “Ginsberg does not teach human parameters
of age, body mass index, and duration of diabetes.” {Id. at 6.) However, the
Examiner finds Ford teaches these parameters to be associated with diabetes
risk and concludes that
[i]t would have been obvious to incorporate the diabetes risk
factors as taught by Ford, in to methods for estimating insulin
for diabetes management as taught by Ginsberg, to obtain the
invention as claimed, because the incorporation of other factors
could produce a more accurate estimation of the insulin
sensitivity factor. There is a likelihood of success of combining
Ford with Ginsberg because both consider patient parameters in
association with diabetes of a patient.
{Id. at 6-7.)
Appellants contend, among other things, that the cited prior art
combination does not teach combining “determined blood glucose
variability with a personal score computed for [a] diabetic human from
parameters including . . . age, body mass index, insulin units per kilogram
weight and the duration of the diabetes . . . to . . . compute an estimate of SI
as claimed.” (Appeal Br. 8-10.)
The issue with respect to this rejection is whether the evidence of
record supports the Examiner’s conclusion that the combination of Ginsberg
and Ford renders obvious the method of computing SI recited in the claims.
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Analysis
We agree with Appellants that the Examiner has not established a
prima facie case that Ginsberg and Ford suggest computing an estimate of SI
by combining blood glucose variability with “a personal score computed . . .
from parameters including [a] diabetic human’s age, body mass index,
insulin units per kilogram weight and the duration of the diabetes in the
diabetic human,” as recited by the claims. (Appeal Br. 12 (Claims App’x).)
As discussed above, the Examiner argues that Ginsberg suggests the
concept of a personal score because Ginsberg teaches providing a patient
with a personalized ISF. (Ans. 5, 10.) The Examiner also appears to
contend that Ginsberg suggests the concept of a personal score computed
from parameters including insulin units per kilogram weight, because (1)
Ginsberg teaches “an amount of insulin administered to the patient during
[a] time period, with respect to a personal CIR, wherein CIR is different for
each person, suggesting weight of the person as a factor in determining a
personal CIR” and (2) “Ginsberg teaches that the insulin sensitivity factor is
individual to the patient and determined over time, wherein a common ISF is
30-50 mg/dL per unit of insulin, wherein the insulin can be provided in
units.” {Id.) Finally, the Examiner concedes that “Ginsberg does not teach
parameters of age, body mass index, and duration of diabetes.” {Id. at 6.)
However, the Examiner argues that Ford “teaches several personal
parameters associated with diabetes risk including body mass index, weight
in kilograms, age, and duration of diagnosis.” {Id. at 6-7.) The Examiner
argues that it would have been obvious to incorporate these parameters into
Ginsberg’s method to arrive at the claimed invention, because “the
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Application 12/665,149
incorporation of other factors could produce a more accurate estimation of
the insulin sensitivity factor.” {Id. at 7, 10.)
We find Appellants have the better position. As an initial matter, we
are not persuaded that Ginsberg discloses the parameter of insulin units per
kilogram weight or that such a parameter should be used in calculating ISF.
The Examiner does not explain why the prior art disclosures that CIR and
ISF may be different for each patient and that insulin may be administered to
patients in units suggest that insulin units per kilogram weight is relevant to
calculating ISF, particularly as Ginsberg does not appear to use the patient’s
weight in calculating either the CIR or the ISF in its method. “[Rejections
on obviousness grounds cannot be sustained by mere conclusory statements;
instead, there must be some articulated reasoning with some rational
underpinning to support the legal conclusion of obviousness.” KSR Int’l Co.
v. Teleflex Inc., 550 U.S. 398, 418 (2007) (internal quotation marks and
citation omitted).
Moreover, although Ford discloses that BMI and weight are
associated with diabetes risk (Ford 1971, col. 3 (“obesity is a powerful
determinant of type-2 diabetes”)), the Examiner has not pointed to
disclosures in Ford suggesting that, for instance, insulin units per kilogram
weight and duration of diabetes are associated with diabetes risk.8 To the
extent that Ford discloses age, BMI, insulin units per kilogram weight and
8 Ford discloses that C-reactive protein concentrations increased with
increasing BMI and were “lowest among those individuals without diabetes
or with impaired fasting glucose and highest among those with newly or
previously diagnosed diabetes.” (Ford 1971, Abstract, Results.) However,
the Examiner does not explain how this finding shows that duration of
diabetes (rather than its existence) is associated with diabetes risk.
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Application 12/665,149
duration of diabetes to be factors associated with diabetes risk, the Examiner
also has not explained why or how such factors may be combined with blood
glucose variability to “produce a more accurate estimation of the insulin
sensitivity factor” discussed in Ginsberg. KSR, 550 U.S. at 418 (2007)
(obviousness rejections require articulated reasoning with rational
underpinning).
In response to Appellants’ arguments, the Examiner clarifies that
Ford teaches that C-reactive protein is associated with diabetic
patients and with insulin concentrations and insulin resistance.
Ford teaches that accurate C-reactive protein concentrations
must be adjusted based on factors such as age, sex, race or
ethnicity, education and BMI, suggesting a plurality of patient
factors should be used to accurately determine insulin
sensitivity factor.
(Ans. 10 (citations omitted).)
We remain unpersuaded. C-reactive protein is “an acute-phase
reactant produced by hepatocytes in response to a wide range of stimuli,” the
concentration of which “rises dramatically in response to infection,
inflammation, and injury.” (Ford 1971, first col.) In discussing the
relationship between C-reactive protein and BMI and diabetes status, Ford
teaches that C-reactive protein concentrations increased with increasing BMI
and were “lowest among those individuals without diabetes or with impaired
fasting glucose and highest among those with newly or previously diagnosed
diabetes” even after adjustment for age, sex, race or ethnicity, education, and
BMI. (Id. at Abstract, Results.) Ford further teaches that C-reactive protein
was positively associated with insulin concentration, glycosylated
hemoglobin concentration, and glucose concentration. (Id. at 1976, right
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Application 12/665,149
col., Table 5.) In suggesting mechanisms that may link obesity and elevated
concentration of C-reactive protein, Ford also stated:
Expression of tumor necrosis factor (TNF)-a and circulating
concentrations of (TNF)-a are increased in obesity. (TNF)-a
can stimulate the production of C-reactive protein, cause insulin
resistance, and promote the production of macrophage
migration inhibitory factor, a proinflammatory cytokine. . . .
C-reactive protein may reflect indirectly the associations
between other factors, such as (TNF)-a . . ., and BMI. Insulin
concentrations, which are often high in individuals with insulin
resistance or in obese individuals, are inversely related, and
glucagon concentrations, which are normal or elevated in obese
individuals, are directly related to C-reactive protein
production.
(Ford 1975, first col.)
As shown by the above summary, Ford’s adjustment for factors such
as age and BMI appears to be for the purpose of controlling potential
confounding variables so as to permit the study the correlation between C-
reactive protein concentration and diabetes status.9 (See also Ford 1976,
cols. 1 and 2 (stating that limitations of the study include “possible
confounders that were not included”).) The Examiner does not explain how
Ford’s controlling for such variables to accurately determine the correlation
between C-reactive protein concentration and diabetes, suggest that these
variable also must be adjusted in order to accurately determine C-reactive
protein concentration, much less why they should be used to compute a
patient’s insulin sensitivity.
9 Confounding variables are variables that may correlate with both the
dependent and independent variable under study, which may thus create
inaccuracies in the perceived existence or degree of correlation between the
dependent and independent variables (e.g., the correlation between C-
reactive protein concentration and diabetes status).
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Accordingly, we reverse the Examiner’s rejection of claims 25, 31-
33, and 39-41.
REVERSED
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