UNIVERSITY OF SOUTHERN CALIFORNIA

Patent Trials and Appeals Board

Nov 13, 2020

2020001711 (P.T.A.B. Nov. 13, 2020)

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.
15/131,586 04/18/2016 VALTER D. LONGO USC0140PUSP 8455
22045 7590 11/13/2020
Brooks Kushman
1000 Town Center
22nd Floor
Southfield, MI 48075
EXAMINER
COFFA, SERGIO
ART UNIT PAPER NUMBER
1658
NOTIFICATION DATE DELIVERY MODE
11/13/2020 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):
docketing@brookskushman.com
kdilucia@brookskushman.com
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
__________

BEFORE THE PATENT TRIAL AND APPEAL BOARD
__________

Ex parte VALTER D. LONGO and STEFANO DI BIASE
__________

Appeal 2020-001711
Application 15/131,586
Technology Center 1600
__________

Before ERIC B. GRIMES, FRANCISCO C. PRATS, and
ULRIKE W. JENKS, Administrative Patent Judges.

PRATS, Administrative Patent Judge.

DECISION ON APPEAL

Pursuant to 35 U.S.C. § 134(a), Appellant1 appeals from the
Examiner’s decision to reject claims 1, 3–8, 15, 17–19, and 22–32. We have
jurisdiction under 35 U.S.C. § 6(b).
We AFFIRM.

STATEMENT OF THE CASE
The sole rejection before us for review is the Examiner’s rejection of
claims 1, 3–8, 15, 17–19, and 22–32, under 35 U.S.C. § 103(a) as being

1 We use the word “Appellant” to refer to “applicant” as defined in 37
C.F.R. § 1.42. Appellant states that the real party in interest is the
University of Southern California. Appeal Br. 1.
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unpatentable over Longo,2 Malik,3 Liu,4 and Pasternak5 (Final Act. 2–7;
Ans. 4–10).
Appellant’s claim 1 is representative and reads as follows:
1. A method for treating a hyperglycemia in a subject
undergoing chemotherapy, the method comprising:
a) identifying a subject undergoing chemotherapy
and having hyperglycemia; and
b) administering short-term starvation (STS), a
fasting mimicking diet (FMD) or insulin to the subject for a
first time period to prevent or reverse hyperglycemia and
sensitization to chemotherapy associated with increased glucose
levels.
Appeal Br. Claims App.
DISCUSSION
The Examiner’s Prima Facie Case
The Examiner cited Longo as teaching that short term starvation
(STS) and fasting mimicking diets (FMD) are useful for treating patients
suffering from chemotoxicity due to chemotherapy. Ans. 5–6. The
Examiner determined therefore, that as required by Appellant’s claim 1,
Longo’s patients “have been identified as undergoing chemotherapy.” Id. at

2 US 2014/0227373 A1 (published Aug. 14, 2014).
3 Ajay K. Malik, Ph.D., The link between diabetes and
breast cancer (http://www.oncologynurseadvisor.com/breastcancer/
the-link-between-diabetes-and-breast-cancer/article/242813) (2012).
4 Yuhong Liu et al., Rapamycin-induced metabolic defects are reversible in
both lean and obese mice, 6 AGING 742–754 (2014).
5 Jeffrey J. Pasternak et al., Effect of Single-Dose Dexamethasone on Blood
Glucose Concentration in Patients Undergoing Craniotomy, 16 J.
NEUROSURGICAL ANESTHESIOLOGY 122–125 (2004) (abstract only).
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5. The Examiner also noted Longo’s disclosure that 5-day dieting
significantly reduced blood glucose. Id. at 8.
The Examiner found that Longo differs from Appellant’s claim 1 in
that Longo “do[es] not teach the [identified] subject has hyperglycemia.”
Ans. 7. To address that difference, the Examiner cited Malik as “teach[ing]
that 16% to 20% of women with breast cancer have diabetes (page 1, 3rd
para)[6], and further teach[es] that the risk of death in early breast cancer
patients increases significantly with hyperglycemia (page 3, last para).” Id.
Based on the combined teachings of Longo and Malik, the Examiner
concluded that it would have been obvious to administer Longo’s STS and
FMD diets “to patients undergoing chemotherapy and having hyperglycemia
because the risk of death in early breast cancer patients increases
significantly with hyperglycemia (taught by Malik).” Ans. 7. The Examiner
reasoned that a skilled artisan
would have been motivated to do so, and reasonably expected
the diet of Longo et al. would have been useful in treating
hyperglycemia (i.e. high blood sugar) and breast cancer because
Longo et al. teach that the progression [of] breast cancer was
strongly inhibited by the low protein diet (para [0104]) and
further teach that the 5-day dieting significantly reduced blood
glucose (para [0139]).
Id. at 7–8
The Examiner cited Liu and Pasternak as evidence that hyperglycemia
is a side effect of the chemotherapeutic drugs rapamycin and
dexamethasone, respectively. Ans. 8. The Examiner reasoned, therefore,

6 The Malik article appears to be scanned from a printed version of an article
on a website. The Examiner appears to cite to the first printed page as page
1, and the remaining pages as if numbered consecutively. We do the same
for consistency.
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that a skilled artisan treating cancer with rapamycin and/or dexamethasone
“would have reasonably expected said patients to have hyperglycemia and
thus would have been motivated to administer the diet of Longo et al. in
order to treat cancer and the hyperglycemia caused by said chemotherapeutic
drugs.” Id. at 8–9.
Analysis
As stated in In re Oetiker, 977 F.2d 1443, 1445 (Fed. Cir. 1992):
[T]he examiner bears the initial burden . . . of presenting a
prima facie case of unpatentability. . . .
After evidence or argument is submitted by the applicant in
response, patentability is determined on the totality of the
record, by a preponderance of evidence with due consideration
to persuasiveness of argument.
In the present case, Appellant does not persuade us that the
Examiner’s conclusion of obviousness as to Appellant’s claim 1 is not
supported by a preponderance of the evidence. In particular, Appellant does
not persuade us that the combined teachings of Longo, Malik, Liu, and
Pasternak fail to suggest claim 1’s step of identifying a subject undergoing
chemotherapy and having hyperglycemia. See Appeal Br. 3–4; Reply Br. 1–
2. Nor does Appellant persuade us that the combined teachings of the cited
references fail to suggest administering STS or an FMD diet to a subject
undergoing chemotherapy and having hyperglycemia. See Appeal Br. 5–6;
Reply Br. 2–3.
Specifically, as the Examiner found, Malik discloses that 16 to 20% of
women with breast cancer have diabetes (i.e. hyperglycemia), and that
“Metformin, a widely used antidiabetic medication, was shown to improve
the breast cancer treatment response rate in type 2 diabetic patients.” Malik
1. Malik discloses that diabetes exacerbates the toxicity of
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chemotherapeutic agents, increasing the risk of hospitalization. See id. at 3
(“Patients with preexisting diabetes may also preclude aggressive or even
optimal cancer treatment due to increased incidence of treatment-related
complications. In addition, these patients have higher risk of
hospitalizations due to chemotherapy-associated toxicities, such as
neutropenia, anemia, or any cause . . . .”) (Citations omitted; emphasis
added).
Malik also discloses that diagnosing hyperglycemia in breast cancer
patients can improve the prognosis of the cancer treatment. See Malik 3 (“It
is estimated that 30% of the patients with chronic hyperglycemia and
symptomless diabetes remain undiagnosed at the time of breast cancer
diagnosis. These breast cancer patients may end up with poor prognosis
which otherwise could have been prevented.”).
Thus, to summarize, Malik teaches that diabetes exacerbates the
toxicity of chemotherapeutic agents, thereby increasing the risk of
hospitalizations, and also teaches that diagnosing hyperglycemia in cancer
patients can improve the prognosis of the cancer treatment. Given these
teachings, we agree with the Examiner that a skilled artisan would have
considered it desirable to identify, among breast cancer patients being
treated with chemotherapy, those patients that also have hyperglycemia, as
recited in Appellant’s claim 1. Because making that identification would
allow a skilled artisan to treat the hyperglycemia, and thereby improve the
prognosis of the cancer treatment, we discern no error in the Examiner’s
determination that Malik would have suggested claim 1’s step of identifying
a subject undergoing chemotherapy and having hyperglycemia.
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In addition, as the Examiner also found, Liu and Pasternak disclose
that hyperglycemia is a side effect of the chemotherapeutic agents
rapamycin and dexamethasone, respectively. See Liu 742 (“[C]hronic
rapamycin treatment causes impairments in glucose metabolism including
hyperglycemia . . . . The reversible nature of rapamycin’s alterations of
metabolic function suggests that these potentially detrimental side-effects
might be managed through alternative dosing strategies or concurrent
treatment.”); Pasternak, abstract (“Dexamethasone, a corticosteroid used to
treat cerebral edema, is known to produce elevations in the blood glucose
concentration . . . .”).
We agree with the Examiner that a skilled artisan would have
considered it desirable to identify, among patients being treated with
rapamycin and/or dexamethasone chemotherapy, those patients that also
have hyperglycemia, as recited in Appellant’s claim 1. Because making that
identification would allow a skilled artisan to treat the hyperglycemia in
addition to the condition treated by the chemotherapy, as taught for example
in Liu, we discern no error in the Examiner’s determination that Liu and
Pasternak would have suggested claim 1’s step of identifying a subject
undergoing chemotherapy and having hyperglycemia. Moreover, given
Malik’s teaching that treating hyperglycemia in cancer patients improves
treatment prognosis, we agree with the Examiner that the combined
teachings of Malik, Liu, and Pasternak provide ample motivation for
performing claim 1’s step of identifying a subject undergoing chemotherapy
and having hyperglycemia.
Although Malik, Liu, and Pasternak do not describe claim 1’s step of
administering STS, an FMD, or insulin, to such a subject, Longo discloses
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that STS and FMD are both useful not only for ameliorating the chemotoxic
effects of chemotherapy, but also for reducing blood glucose. See Longo
¶ 157 (“Short-term starvation (STS) reduces serum levels of glucose and
IGF-1, increases cellular protection against high-dose chemotherapy, and
sensitizes malignant cells to chemotherapeutic drugs.”); id. ¶ 139 (“Human
subjects participated in 3 cycles of a low protein low calorie and high
nourishment 5-day fasting mimicking diet (FMD . . .) followed by
approximately 3 weeks of normal diet . . . . The 5-day dieting significantly
reduced blood glucose . . . .”); id. ¶ 76 (disclosing that providing low protein
FMD diet results in “alleviating a symptom of chemotoxicity in a subject”).
Because Longo discloses that both STS and FMD are beneficial for
ameliorating the chemotoxic effects of chemotherapy, as well as for
reducing blood glucose, we agree with the Examiner that a skilled artisan
had a good reason for, and a reasonable expectation of success in,
administering STS or FMD to a subject receiving chemotherapy who was
also identified as having hyperglycemia, as recited in Appellant’s claim 1.
Appellant does not persuade us, therefore, that the Examiner erred in
determining that the combined teachings of Longo, Malik, Liu, and
Pasternak would have suggested a process having all of the steps and
features required by Appellant’s claim 1.
Appellant also does not persuade us that it has presented evidence of
unexpected results sufficient to outweigh the prior art evidence of
obviousness, discussed above, advanced by the Examiner. While we
acknowledge the positive attributes of the FMD diet described in Exhibit A
to the Appeal Brief, and Appellant’s assertion of the diet’s “unexpected
health benefits” described in Exhibit A (Appeal Br. 4), Appellant does not
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explain specifically how any of the information in Exhibit A relates to the
process of Appellant’s claim 1.
Appellant contends that it is unexpected that administering STS,
FMD, or insulin, reduces hyperglycemia-associated sensitivity to
chemotherapy. See Appeal Br. 4–5 (citing Spec. ¶ 63 and Figs. 1C and 1D).
We are not persuaded.
As an initial matter, we note that the Specification does not state that
the effects described in ¶ 63 and Figures 1C and 1D were surprising or
unexpected. Rather, on the current record, the sole assertion of
unexpectedness in relation to the results described in ¶ 63 and Figures 1C
and 1D appears in Appellant’s briefs. It is well settled that, by themselves,
assertions in briefing by counsel as to the unexpectedness of experimental
results are of little probative value toward nonobviousness, absent some
evidence, beyond the assertions in the briefs, that a skilled artisan actually
would have considered the results unexpected. See In re Geisler, 116 F.3d
1465, 1470–71 (Fed. Cir. 1997) (finding arguments of unexpected results
unpersuasive “naked attorney argument” because applicant “did not offer
evidence of unexpected results in the form of a statement to that effect from
the inventors or any third party, or any objective evidence from a respected
source” nor did applicant make any statements of unexpectedness in its
specification or in an affidavit under 37 C.F.R. § 1.132).
It is also well settled that “any superior property must be unexpected
to be considered as evidence of non-obviousness.” Pfizer, Inc. v. Apotex,
Inc., 480 F.3d 1348, 1371 (Fed. Cir. 2007).
In the present case, as the Examiner notes, and as discussed above,
Malik discloses that hyperglycemia is associated with a poor prognosis in
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breast cancer treatment. In addition, as also discussed above, Longo
discloses that administering the STS and FMD diets reduces chemotoxicity
associated with chemotherapy, in addition to reducing blood glucose. We
are not persuaded, therefore, that Appellant has explained sufficiently why a
skilled artisan would have considered it unexpected that the STS and FMD
diets would be beneficial when administered to chemotherapy-receiving
hyperglycemic patients, or that survival rates in such patients would be
significantly increased by the diets.
We acknowledge Appellant’s assertion that “[i]t is evident from these
results [shown in Figures 1C and 1D] that short term starvation spectacularly
improves survival for situations in which hyperglycemia is induced (greater
than 80% versus less than 10%).” Appeal Br. 5. Longo, however, discloses
that in experiments in mice similar to those for which Appellant asserts
unexpected results, fasting improves the chemotherapy survival rate to a
degree similar to that shown in Figures 1C and 1D:
Mice fed ad lib with the [standard chow] AIN93G diet 3 days
prior to DXR injection showed the worst outcome with only
16% surviving by day 25 (FIG.24A). In contrast to the ad lib
fed mice, the great majority (89%) of fasted (60 hours) mice
survived the high-dose [doxorubicin] chemotherapy.
Longo ¶ 165. Given Longo’s disclosure that fasted mice survive high dose
doxorubicin chemotherapy at a rate similar to the survival rate shown in
Figures 1C and 1D for mice treated with dexamethasone and rapamycin, we
are not persuaded that Appellant has explained sufficiently why a skilled
artisan would have considered the results shown in Appellant’s Figures 1C
and 1D to be unexpected.
In sum, for the reasons discussed, Appellant does not persuade us that
the Examiner erred in determining that Longo, Malik, Liu, and Pasternak
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would have provided a skilled artisan with motivation for, and a reasonable
expectation of success in, administering STS and FMD diets to
chemotherapy-receiving subjects identified as having hyperglycemia, as
recited in Appellant’s claim 1. For the reasons discussed, we are not
persuaded that Appellant has advanced evidence of unexpected results
sufficient to outweigh the prior art evidence of prima facie obviousness
presented by the Examiner. Because a preponderance of the evidence
therefore supports the Examiner’s conclusion that the process recited in
Appellant’s claim 1 would have been obvious over Longo, Malik, Liu, and
Pasternak, we affirm the Examiner’s rejection of claim 1 over those
references.
Appellant contends that a number of claims are independently
patentable over Longo, Malik, Liu, and Pasternak. See Appeal Br. 6–7. We
are not persuaded.
As explained in our rules, “[a] statement which merely points out
what a claim recites will not be considered an argument for separate
patentability of the claim.” 37 C.F.R. § 41.37(c)(1)(iv).
In asserting that claim 4 is independently patentable over the cited
references, Appellant argues as follows:
Claim 4 is directed solely to the administration of the
fasting mimicking diet . . . “for 48-140 hours prior to a round of
chemotherapy and/or 4-56 hours following a round of
chemotherapy.” Since claim 4 depends from claim 1, the
subject being treated satisfies both of the following conditions -
undergoing chemotherapy and having hyperglycemia. As
explained above, none of Longo, Malik, Liu, and Pasternak
recognize a benefit for treating a subject satisfying both of these
conditions. Accordingly, claim 4 is independently allowable
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under 35 U.S.C. 103 over Longo in view of Malik, Liu, and
Pasternak.
Appeal Br. 6. Similarly, in arguing that claims 23, 26, 27, and 28 are
independently patentable over Longo, Malik, Liu, and Pasternak, Appellant
merely restates the limitations of claims 23, 26, 27, and 28, and reiterates
substantially the same arguments advanced against the rejection of claim 1.
See id. at 7.
Thus, in contending that claims 4, 23, 26, 27, and 28 are separately
patentable from claim 1, Appellant merely restates the limitations of those
dependent claims, but fails to advance any argument explaining with
particularity why processes having the specific limitations in those
dependent claims would be patentable for reasons distinct from the reasons
advanced as to claim 1. We are not persuaded, therefore, that Appellant has
explained sufficiently why claims 4, 23, 26, 27, and 28 are separately
patentable from claim 1.
In sum, for the reasons discussed, we affirm the Examiner’s rejection
of claim 1 over Longo, Malik, Liu, and Pasternak. Because they were not
argued separately, claims 3–8, 15, 17–19, and 22–32 fall with claim 1. See
37 C.F.R. § 41.37(c)(1)(iv).
DECISION SUMMARY
In summary:
Claims
Rejected
35 U.S.C.
§
Reference(s)/Basis Affirmed Reversed
1, 3–8, 15,
17–19, 22–
32
103(a) Longo, Malik, Liu,
Pasternak
1, 3–8, 15,
17–19, 22–
32

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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). See 37 C.F.R.
§ 1.136(a)(1)(iv).

AFFIRMED