Valter Longo et al.

Patent Trials and Appeals Board

Dec 15, 2020

2020002584 (P.T.A.B. Dec. 15, 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.
13/643,673 10/26/2012 Valter D. Longo USC 0109 PUSA 9161
22045 7590 12/15/2020
Brooks Kushman
1000 Town Center
22nd Floor
Southfield, MI 48075
EXAMINER
SAOUD, CHRISTINE J
ART UNIT PAPER NUMBER
1647
NOTIFICATION DATE DELIVERY MODE
12/15/2020 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 JAIME GUEVARA

Appeal 2020-002584
Application 13/643,673
Technology Center 1600
Before ERIC B. GRIMES, ULRIKE W. JENKS, and JAMIE T. WISZ,
Administrative Patent Judges.

WISZ, Administrative Patent Judge.

DECISION ON APPEAL

Appeal 2020-002584
Application 13/643,673

2
STATEMENT OF THE CASE
Pursuant to 35 U.S.C. § 134(a), Appellant1 appeals from the
Examiner’s decision to reject claims 1–3, 5, 8–15, 17, 20–26, and 31–39.
We have jurisdiction under 35 U.S.C. § 6(b).
We AFFIRM.
CLAIMED SUBJECT MATTER
The Specification describes “methods of reducing the deleterious
effects of aging, oxidative damage and chemotherapy in a subject and
preventing and/or alleviating a symptom of age related diseases.” Spec. ¶ 3.
Such methods comprise administering a therapeutically effective amount of
a growth hormone (GH)/insulin like growth-factor-I (IGF-I) Axis inhibitory
composition to a subject so that IGF-I levels are reduced. Id. ¶ 6. Claim 1 is
illustrative of the claimed subject matter and is reproduced below:
1. A method of increasing survival in a subject undergoing
chemotherapy, the method comprising:
identifying a subject undergoing chemotherapy with a
chemotherapeutic agent that damages DNA;
administering of a GH/IGF-1 Axis inhibitory
composition to the subject, the GH/IGF-1 Axis inhibitory
composition being administered in an amount such that the
subject’s plasma IGF-1 level is from 20 to 60 percent of the
subject’s baseline plasma IGF-1 level, the baseline plasma
IGF-1 level being a value of the plasma IGF-1 level prior to
treatment; and
measuring the level of IGF-1 in the subject.
Appeal Br., Claims App. 1.

1 We use the word “Appellant” to refer to “applicant” as defined in
37 C.F.R. § 1.42. Appellant identifies the real party in interest as the
University of Southern California. Appeal Br. 1.
Appeal 2020-002584
Application 13/643,673

3
REJECTIONS
The Examiner rejected claims 1–3, 5, 8–15, 17, 20–26, and 31–39 for
lack of enablement.
The Examiner rejected claims 8, 10–13, 15, 20, 25, 26, and 392 under
35 U.S.C. § 102(a) as anticipated by Trainer.3
ISSUES AND ANALYSIS
Rejection of Claims 1–3, 5, 8–15, 17, 20–26, and 31–39 for Lack of
Enablement.
Claims 1–3, 5, 31–38
The Examiner finds that claims 1–3, 5, and 31–38 “are not enabled for
the claimed method because there is no evidence that administration of a
GH/IGF-1 Axis Inhibitory composition will increase the survival of a subject
undergoing chemotherapy.” Final Act. 3–4. The Examiner finds that,
although the “specification does teach generation of antibodies to growth
hormone in a mouse and then administration of cyclophosphamide (a
chemotherapeutic) in an experiment to demonstrate a protective effect of
GH/IGF-1 Axis inhibition,” the
specification does not provide any statistical data to evaluate
with regard to body weight evaluations or IGF-1 levels and the
administration of cyclophosphamide is not predictive of all
chemotherapy treatments and generation of antibodies to growth
hormone in a mouse is not predictive of administration of any

2 The rejection of claims 14 and 21–24 under 102(b) as being anticipated by
Trainer were withdrawn. Ans. 8.
3 Trainer et al., “Treatment of Acromegaly with the Growth Hormone-
Receptor Antagonist Pegvisomant,” N. Engl. J. Med. 342: 1171–1177
(2000) (“Trainer”).
Appeal 2020-002584
Application 13/643,673

4
GH/IGF-1 Axis inhibitory composition and also not predictive of
Pegvisomant™ administration.
Id. at 4.
The Examiner further finds that Longo4 “teaches that GH/IGF-1 Axis
inhibition is not sufficient to increase the survival of a subject undergoing
chemotherapy” because Longo “clearly indicates that the GH/IGF-1 Axis
inhibitor alone was not sufficient to protect against the toxicity of the
chemotherapeutic.” Id. (citing Longo ¶ 141). The Examiner concludes:
One of ordinary skill in the art would not find the cell data
presented in the instant specification predictive of increasing
survival in a subject undergoing chemotherapy because in vitro
data on cell survival would not be found predictive of survival of
a subject undergoing chemotherapy, absent evidence to the
contrary.
Id.
Appellant asserts that the application “provides numerous examples
that implicate GH/IGF-1 Axis inhibition in increasing survival and reducing
the incidence of cancer” for example as shown in Figures 14A and 14B.
Appeal Br. 3 (citing Spec. ¶¶ 28, 92, Figs. 13B, 14A, 14B). According to
Appellant, in these experiments, “the short term immunization with growth
hormone leads to the production of antibodies to growth hormone” which
“are proof positive of the beneficial effects of the administration of a
GH/IGF-1 Axis inhibitory composition.” Id. at 3–4.
Appellant also points to Figure 16 as “[a]dditional experimental
results showing that administration of a GH/IGF-1 Axis inhibitory
composition increases survival in a subject undergoing chemotherapy.” Id.
at 4 (citing Spec. ¶ 94, Fig. 16). Appellant further contends that “the studies

4 Valter Longo, US 2008/0242638 A1, published Oct. 2, 2008 (“Longo”).
Appeal 2020-002584
Application 13/643,673

5
of the population of individuals from Ecuador with growth hormone receptor
deficiency showing a reduced incidence of cancer and no cancer deaths are
particularly relevant” and “provides the nexus or correlation with the
benefits of reducing IGF-1 levels and increasing survival.” Id. at 5.
According to Appellant, the “results presented in Figure 1 for the Ecuadorian
GHRD cohort show a very strong correlation with Growth Hormone
Receptor Deficiency (GHRD) and a decreased risk of death from cancer.”
Id. (citing Spec. ¶ 67, Fig. 1E).
Appellant concludes that “[w]hen the results of Figures 1, 14, and 16
are collectively analyzed, there can be little doubt that administration of
GH/IGF-1 Axis inhibitory composition to a cancer subject undergoing
chemotherapy results in increased survival.” Id. at 7. Appellant also cites to
MPEP 2164.02 which states,
“[a]n in vitro or in vivo animal model example in the
specification, in effect, constitutes a ‘working example’ if that
example ‘correlates’ with a disclosed or claimed method
invention. . . . [T]he issue of ‘correlation’ is also dependent on
the state of the prior art.” “[I]f the art is such that a particular
model is recognized as correlating to a specific condition, then it
should be accepted as correlating unless the examiner has
evidence that the model does not correlate.”
Id. (citation omitted). Appellant argues that “[i]t is the examiner who ‘must
also give reasons for a conclusion of lack of correlation for an in vitro or in
vivo animal model example. A rigorous or an invariable exact
correlation is not required, as stated in Cross v. Jizuka, 753 F.2d 1040,
1050, 224 USPQ 739, 747 (Fed. Cir. 1985).’” Id. (citing MPEP 2164.02)
(emphasis added).

Appeal 2020-002584
Application 13/643,673

6
Appellant also asserts that the Examiner inappropriately applied
Longo. Reply Br. 5. According to Appellant, Longo states that the
GH/IGF-1 Axis inhibitory composition (i.e., octreotide) had a “relatively
modest effect . . . on the reduction of circulating IGF-I level,” therefore, the
discrepancy of octreotide’s ability to provide protection in vitro, which was
not seen in vivo, “can be explained by a failure of octreotide to reach the
claimed plasma IGF-1 level.” Id. (citing Longo ¶ 141).
Appellant also contends that the only reference to the survival of a
subject undergoing chemotherapy in claim 1 is in the preamble. Id.
According to Appellant, “claim 1 sets out all the limitations of the invention
while the preamble merely presents an intended use” and, therefore, the
preamble should not be used to reject the claims. Id. at 7–8 (citing MPEP
2111.02).
The Examiner responds that:
Immunization of mice against human growth hormone and then
administering cyclophosphamide treatment and showing
changes in complete blood count is not predictive of increasing
survival in a subject undergoing chemotherapy. Additionally,
experiments of increasing survival of stem cells in culture is not
predictive of increasing the survival of a subject undergoing
chemotherapy as broadly claimed, especially in light of [Longo].
. . . [Longo] teaches that GH/IGF-1 Axis inhibition is not
sufficient to increase the survival of a subject undergoing
chemotherapy.
Ans. 9–10. The Examiner further finds that, “[i]ncreasing survival of stem
cells in a dish is not predictive of increasing the survival of a subject
undergoing chemotherapy as a stem cell is not a subject nor do stem cells
correlate to treating a subject.” Id. at 11.
Appeal 2020-002584
Application 13/643,673

7
With regard to the studies of the Ecuadorian cohort, the Examiner
responds that:
While the subjects referenced and studied with growth hormone
receptor deficiency have a reduced incidence of cancer, it is
unknown what other genetic alterations are present in this
population which might have an effect on the incidence of
cancer. A correlation of this deficiency with a reduced incidence
of cancer is not evidence of a causal relationship.
Id. at 10.
Lastly, in response to Appellant’s arguments regarding the preamble,
the Examiner finds that “[i]ntended use generally refers to products and not
to methods” and that “[t]he instant claims are directed to methods which are
intended to have a particular outcome.” Id.
On this record, we find that the Examiner has the better position. We
agree with the Examiner that the data relied on in the Specification does not
provide an enabling disclosure of a method of increasing survival in a
subject undergoing chemotherapy by reducing the plasma level of IGF-1
levels to 20 to 60 percent of a subject’s baseline plasma IGF-1 level through
the administration of a GH/IGF-1 Axis inhibitory composition.
Specifically, Appellant has not provided persuasive evidence or
argument that the data in Figure 14A showing the body weight of mice
treated with human growth hormone (GH) after cyclophosphamide (CP)
treatment is predictive of increasing survival in a subject undergoing
chemotherapy using any chemotherapeutic agent that damages DNA.
Appellant has also not shown that the specifically recited plasma IGF-1
levels of 20 to 60 percent of a subject’s baseline plasma IGF-1 level are
effective at increasing survival in a subject undergoing chemotherapy.
Appeal 2020-002584
Application 13/643,673

8
Appellant has not pointed to any data in the Specification which provides
evidence of the effectiveness of these recited plasma IGF-1 levels.
Similarly, Appellant has not provided persuasive evidence that the
data in Figure 14B showing the complete blood count in GH-treated mice
after CP treatment is predictive of increasing survival in a subject
undergoing chemotherapy when the plasma IGF-1 level is reduced to the
levels as claimed. Appellant has also not provided any persuasive evidence
that the in vitro data in Figure 16 showing the amount of stem cells treated
with an inhibitory antibody that blocks the IGF-I receptor after treatment
with CP is predictive of increasing survival in a subject undergoing
chemotherapy.
Although the data in the Specification may provide some evidence of
a protective effect of an inhibitory antibody that blocks the IGF-1 receptor,
the data provided is not commensurate in scope with the claims. The data
only shows the protective effects of an inhibitor antibody while the claims
recite administration of any GH/IGF-1 inhibitory composition. In addition,
the data only shows a protective effect against the chemotherapy drug
cyclophosphamide while the claims recite any chemotherapeutic agent that
damages DNA. Furthermore, the data does not provide any indication of
IGF-1 levels after treatment with an inhibitory antibody so it is not clear
whether the recited range of a plasma IGF-1 level that is 20 to 60 percent of
a subject’s baseline level, would be effective at increasing survival in a
subject undergoing chemotherapy. Furthermore, as discussed above,
Appellant has not persuasively shown how the data in the Specification is
predictive of increasing such survival.
Appeal 2020-002584
Application 13/643,673

9
We also agree with the Examiner that the data on the Ecuadorian
cohort does not provide a causal relationship between a reduced incidence of
cancer and a growth hormone receptor deficiency. Even if such a
relationship were shown, the data does not show that administration of a
GH/IGF-1 inhibitory composition to a subject will result in increasing
survival in a subject undergoing chemotherapy. Even assuming arguendo
that a growth hormone receptor deficiency may result in less deaths due to
cancer, this does not mean that a subject who already has cancer and is
undergoing chemotherapy will have a higher rate of survival if administered
a GH/IGF-1 inhibitory composition.
We further agree with the Examiner that “the claim preamble is
‘necessary to give life, meaning, and vitality’ to the claim,” therefore, it
cannot be excluded when interpreting claim 1. Pitney Bowes Inc. v. Hewlett
Packard Co., 182 F.3d 1298, 1305 (Fed. Cir. 1999). Furthermore,
“[it is a] general principle, as well-settled as any in our patent law
precedent, that a claim preamble has the import that the claim as
a whole suggests for it. In other words, when the claim drafter
chooses to use both the preamble and the body to define the
subject matter of the claimed invention, the invention so defined,
and not some other, is the one the patent protects.”
Bell Commc’ns Research Inc. v. Vitalink Commc’ns Corp., 55 F.3d 615, 620
(Fed. Cir. 1995).
Therefore, claim 1, as properly construed, recites a method for
increasing survival in a subject undergoing chemotherapy, and, for the
reasons discussed above, the Specification does not enable the full scope of
the claim.
Appeal 2020-002584
Application 13/643,673

10
Claims 3 and 15
The Examiner also finds that claims 3 and 15 are not enabled because
the Specification does not enable the claimed growth hormone variants.
Final Act. 4. According to the Examiner, “[t]he only substitution in the list
that provides for an inhibitory molecule is G120R, therefore, any variant that
does not include this substitution would not function as an inhibitory
molecule.” Id.
Appellant contends that “the experimental results of Figures 13 and 14
[demonstrate] that immunization with human group hormone mitigates the
effects of chemotherapy through the generation of antibodies.” Appeal Br.
9. Appellant also asserts that “the variants of claims 3 and 15, when
properly administered, will be a GH/IGF-1 Axis inhibitory composition”
because “at the very least, these variants will induce antibody production.”
Id. Appellant also asserts that the human growth hormone variants of claims
3 and 15 are provided in U.S. Pat. Nos. 5,849,535; 6,004,931; 6,057,292;
6,136,563; 7,470,779; 7,470,779; 7,524,813 and 6,583,115, which have been
incorporated by reference. Id.
The Examiner responds that:
The set of substitutions consisting of H18D, H21N, R167N,
K168A, D171S, K172R, E174S and I179T increases the binding
affinity for the hGH receptor at Site 1 and an hGH variant
including these substitutions acts as an hGH agonist in the
absence of an additional modification that disrupts binding to the
hGH receptor at Site 2 (see [Cunningham]5 at column 4, lines 13-
23). The substitution of a different amino acid at G120 is one
modification that disrupts Site 2 binding and accordingly, an
hGH variant including an amino acid substitution at G120 acts

5 Cunningham et al., U.S. Patent No. 5,849,535, issued Dec. 15, 1998
(“Cunningham”).
Appeal 2020-002584
Application 13/643,673

11
as an hGH antagonist (see [Cunningham] at column 4, lines 24-
27). Therefore, the claims are not enabled for an inhibitory
molecule if the human GH variant includes at least one amino
acid substitution and that “at least one amino acid substitution”
is not G120R. This substitution is necessary for the molecule to
be an antagonist as evidenced by U.S. Pat. No. [Cunningham]
(cited by Appellant).
Ans. 12–13.
On this record, we find that the Examiner has the better position. We
agree with the Examiner that Cunningham, cited by Appellant, teaches that
the human growth factors variants recited in claims 3 and 15 (with the
exception of G120R) act as hGH agonists in the absence of an additional
modification that disrupts binding to the hGH receptor at Site 2. See
Cunningham 4:10–27. Therefore, we agree with the Examiner that these
claims are only enabled with respect to the G120R variant and not for the
other recited variants.
Claims 8–15
The Examiner further finds that claims 8–15, which are directed to
methods of reducing oxidative damage in a subject by administering a
GH/IGF-1 Axis inhibitory composition, are not enabled because a reduction
of IGF-1 levels, as required by the claims, would be sufficient to cause
hyperglycemia which induces oxidative stress and damage. Final Act. 5
(citing Sharma6). The Examiner also finds that because the claims are
directed to reduction of oxidative damage, they encompass a method of
inhibiting aging. Id. According to the Examiner:
The instant specification fails to enable a method of reducing
oxidative damage in a subject as currently claimed because there

6 Sharma et al., “Hyperglycemia Induces Oxidative Stress and Impairs
Axonal Transport Rates in Mice,” PLoS ONE 5(10), 1–8 (2010) (“Sharma”).
Appeal 2020-002584
Application 13/643,673

12
is no nexus between the experiments which were performed and
the outcome of reducing oxidative damage in a subject by
administering a GH/IGF-1 Axis inhibitory composition wherein
the composition is administered in an amount such that the
subject's plasma IGF-1 level is from 20 to 60 percent of the
subject's baseline plasma IGF-1 level.”
Id. at 5. The Examiner also finds that the claims “do not indicate a time
course for the administration, so it is not clear if a single bolus of inhibitor
would be administered such that the claims intend a reduction of oxidative
damage for a given time point.” Id. at 5–6. According to the Examiner, “[i]f
the claims intend general, long term reduction in oxidative damage, then the
claims appear to be directed to inhibition of aging as those skilled in the art
equate reducing ‘oxidative damage’ to the oxidative stress theory of aging,”
which is not supported by the Specification. Id. at 6.
Appellant asserts that the experimental results of Figures 14, 16, and
17 “contradict the Final Office Actions assertion since the administration of
a GH/IGF-1 Axis inhibitory composition decreases the effects of
chemotherapeutic agent that are caused by oxidative damage.” Appeal Br.
10 (citing Spec. ¶ 95, Figs. 14, 16, 17). Appellant also contends that the
Examiner “has not provided any reference that the level of IGF-1 used in the
present invention would cause hyperglycemia.” Id.
The Examiner responds that the statement regarding hyperglycemia
“is based on the known biological principles of the actions of IGF-1 on
Appeal 2020-002584
Application 13/643,673

13
blood glucose and insulin” and cites to Clemmons7 and Weroha8 in support
of this contention. Ans. 13–14. With regard to the data in Figures 14 and
16, the Examiner finds that “[w]hile the cell data may demonstrate reduced
oxidative damage, this is not predictive of treating an intact organism” and
cites to Weroha “which demonstrates that that IGF-1 inhibition results in
hyperglycemia and hyperglycemia causes oxidative damage.” Id. at 14
(citing Clemmons 622).
On this record, we find that the Examiner has the better position. For
many of the reasons discussed above with regard to claim 1, we find that the
data in the Specification does not support the breadth of the claims, which
recite a method for reducing oxidative damage in a subject by reducing a
subject’s plasma IGF-1 level from 20 to 60 percent of the subject’s baseline
plasma levels. Appellant has not persuasively shown that the data in Figures
14A, 14B, and 16 is predictive of reducing oxidative damage in a subject.
Furthermore, the Examiner presents evidence (i.e., Sharma, Clemmons,
Weroha9), unrebutted by Appellant, that administration of a GH/IGF-1
inhibitory composition could actually increase oxidative damage in a
subject.

7 David R. Clemmons, “Involvement of insulin-like growth factor-I in the
control of glucose homeostasis,” Curr. Opin. Pharmacol. 6:620–625 (2006)
(“Clemmons”).
8 Weroha et al., “IGF-1 Receptor Inhibitors in Clinical Trials–Early
Lessons,” J. Mammary Gland Biol. Neoplasia 13(4): 471–483 (2008)
(“Weroha”).
9 Weroha et al., “IGF-1 Receptor Inhibitors in Clinical Trials–Early
Lessons,” J. Mammary Glabd Biol. Neoplasia, 13(4): 471–483, 2008
(“Weroha”).
Appeal 2020-002584
Application 13/643,673

14
The additional data presented in Figure 17 of the Specification does
not cure these deficiencies. Although Figure 17 may show some beneficial
effect from insulin-like growth factor-binding protein 1 (IGFBP1), it is silent
with respect to the effect of insulin-like growth factor-binding protein 2
(IGFBP2), which is described at paragraph 95 of the Specification but does
not appear to be depicted in Figure 17. See Spec. ¶ 95, Fig. 17. The
Specification also fails to provide sufficient experimental details regarding
the data presented in Figure 17. Without such details, it is unknown how
much insulin-like growth factor-binding protein was administered and over
what period of time or how much such administration may have reduced
IGF-1 levels. Appellant has not presented sufficient evidence that this data
regarding primary glial cells in vitro correlates to reducing oxidative damage
in a subject by administering a GH/IGF-1 Axis inhibitory compound so that
the subject’s plasma IGF-1 level is from 20 to 60 percent of the subject’s
baseline IGF-1 level.
Appeal 2020-002584
Application 13/643,673

15
Claims 20–26 and 39
The Examiner also finds that claims 20–26 and 39, which are directed
to methods for reducing risk of cancer in a subject by administering a
GH/IGF-1 Axis inhibitory composition, are not enabled because the
“specification fails to provide a nexus between all cancers and the GH/IGF-1
Axis such that one would have a reasonable expectation that administration
of a GH/IGF-1 Axis inhibitory composition would be useful for reducing the
risk of cancer.” Final Act. 6. The Examiner notes that the Specification
refers to a population of individuals from Ecuador with growth hormone
receptor deficiency (GHRD), which results in reduced IGF-1 levels. Id.
However, the Examiner finds that:
It is not known why the GHRD individuals have a reduced risk
of cancer or how the altered GH receptor functionality influenced
the development of the individuals such that they did not present
with cancer but while there is an association of reduced IGF-I
levels in these patients with a reduced risk of cancer, this does
not equate to a method of reducing the risk of cancer by the
administration of a GH/IGF-1 Axis inhibitory composition as
there is no evidence that administration of such would reduce the
risk of cancer, absent evidence to the contrary.
Id. at 6–7.
Appellant contends that claim 20 does not call for a method of
preventing cancer but, rather, recites a “method for reducing a risk of
cancer in a subject” and many methods are known for reducing the risk of
cancer. Appeal Br. 11. Appellant also asserts that “the study of the
population of individuals from Ecuador with growth hormone receptor
deficiency… provides the nexus or correlation with the benefits of reducing
IGF-I levels and reduced cancer risk.” Id.
Appeal 2020-002584
Application 13/643,673

16
The Examiner responds that the claims encompass and include
prevention of cancer and finds that “there currently are no known methods in
the art for eliminating the risk of developing any and all cancers, absent
evidence to the contrary.” Ans. 15. The Examiner reiterates that “the
specification fails to provide a nexus between all cancers and the GH/IGF-1
Axis such that one would have a reasonable expectation that administration
of a GH/IGF-1 Axis inhibitory composition would be useful for reducing the
risk of cancer.” Id. In response, Appellant also points to Figure 16 of the
Specification, which Appellant asserts “demonstrates increased survival
associated [with] human stem cells that are treated with growth hormone
antibodies.” Reply Br. 7.
On this record, we find that the Examiner has the better position. For
many of the reasons discussed above with regard to claim 1, we find that the
data in the Specification does not support the breadth of the claims, which
recite a method for reducing a risk of cancer in a subject by reducing a
subject’s plasma IGF-1 level from 20 to 60 percent of the subject’s baseline
plasma levels. We agree with the Examiner that the data from the
Ecuadorian cohort is not probative because it does not show that
administration of a GH/IGF-1 inhibitor to achieve a particular plasma IGF-1
level in a subject will reduce a risk of cancer in a subject. Although
Appellant asserts that the individuals from Ecuador with growth hormone
receptor deficiency provides the nexus or correlation with the benefits of
reducing IGF-I levels and reduced cancer risk, we agree with the Examiner
that a “correlation of this deficiency with a reduced incidence of cancer is
not evidence of a causal relationship.” Ans. 15–16. Also, there is no
evidence that administering a GH/IGF-1 inhibitor would result in a similar
Appeal 2020-002584
Application 13/643,673

17
clinical outcome as having a receptor deficiency and any downstream effects
such deficiency might cause.
For the reasons described herein and those already of record, we
sustain the Examiner’s rejection of 1–3, 5, 8–15, 17, 20–26, and 31–39 for
lack of enablement.

Rejection of Claims 8, 10–13, 15, 20, 25–26, and 39 under 35 U.S.C.
§ 102(a) as Anticipated by Trainer
The Examiner finds that Trainer teaches administration of
Pegvisomant to patients with acromegaly wherein the patients have IGF-I
levels which are at least 1.3 times the upper limit of the age-adjusted normal
range and the “treatment with Pegvisomant™ resulted in reduction of IGF-I
from baseline to varying degrees based on the dosage that was administered,
but ranged from 21% to 62% of baseline.” Final Act. 10 (citing Trainer
1172, Table 2). The Examiner further finds that, because Trainer teaches the
levels of IGF-I following administration of Pegvisomant, “the method
clearly measures the IGF-I levels in the subjects.” Id.
The Examiner acknowledges that Trainer does not disclose a
reduction in oxidative damage to the cells, but finds that “this result would
be inherent as it is a property of GH/IGF-1 Axis inhibitory compositions,
absent evidence to the contrary.” Id. The Examiner also acknowledges that
Trainer does not disclose if the patients were predisposed to stroke, cancer,
or diabetes, but finds that “these are diseases for which a great many
individuals are predisposed to and it would be fair to conclude that at least
one of the 80 patients [from Trainer] met these limitations.” Id. at 10–11.
The Examiner further acknowledges that Trainer does not teach that
Appeal 2020-002584
Application 13/643,673

18
administration of Pegvisomant reduced a risk of cancer but finds that “the
steps of the claimed method are anticipated by [Trainer] therefore, the
method of [Trainer] would inherently result in the claimed method, absent
evidence to the contrary.” Id. at 12.
Appellant asserts that, with regard to claim 8, Trainer does not provide
any teaching regarding oxidative damage and the Examiner has not provided
any teaching that acromegaly is associated with oxidative damage. Appeal
Br. 12. Appellant contends that the Examiner improperly applies the
doctrine of inherency because the Examiner “must provide a basis in fact
and/or technical reasoning to reasonably support the determination that the
allegedly inherent characteristic necessarily flows from the teachings of the
applied prior art.” Id. at 13 (citing Ex parte Levy, 17 USPQ2d 1461, 1464
(Bd. Pat. App. & Inter. 1990). Appellant also asserts that claim 8 recites a
step of “identifying a subject predisposed to oxidative damage,” which is not
disclosed in Trainer. Id. Appellant further asserts that claim 20 recites the
step of “identifying a subject predisposed to developing cancer,” which is
not taught by Trainer. Id. at 14–15.
The Examiner responds that every subject is predisposed to oxidative
damage because “oxidative damage is caused by oxidative stress which
occurs when there is an imbalance between the production of free radicals
and the body’s ability to counteract their damaging effects through
neutralization with antioxidants” and “every individual has cells and tissues
which produce free radicals.” Ans. 16. Therefore, according to the
Examiner, the identifying step would be met as every subject would be
identified. Id. at 16–17. With regard to the claims requiring predisposition
to stroke, cancer, or diabetes, the Examiner finds that “it is well-documented
Appeal 2020-002584
Application 13/643,673

19
in the medical community that subjects with acromegaly are predisposed to a
number of health conditions which include cancer, diabetes, cardiovascular
disease, high blood pressure and therefore, stroke.” Id. (citing DeGroot10
304, Table 22-6). According to the Examiner, “[a]s the subjects of [Trainer]
were diagnosed with acromegaly, they necessarily would be predisposed to
stroke, cancer and diabetes as these are known risks of subjects with long-
term exposure to elevated growth hormone levels.” Id. at 17.
On this record, we find that the Examiner has the better position.
Trainer discloses the administration of a GH/IGF-I Axis inhibitory
compound (Pegvisomant) to individuals with acromegaly in order to reduce
hypersecretion of growth hormone to levels that are from 20 to 60 percent of
the subject’s baseline plasma IGF-1 level. See Trainer 1171, 1173, Table 2.
We agree with the Examiner that the identification of individuals with
acromegaly results in the identification of subjects predisposed to oxidative
damage because all individuals have cells and tissues that produce free
radicals and, therefore, are predisposed to oxidative damage. See Ans. 16.
Also, even though Trainer does not specifically disclose the reduction of
oxidative damage, it discloses all the steps of the claimed method and,
therefore, inherently discloses such a result. Discovery of a property
inherent to a prior art process does not render that process patentable, even if
the prior art did not appreciate the property. Verdegaal Bros. Inc. v. Union
Oil Co., 814 F.2d 628, 633 (Fed. Cir. 1987).
Furthermore, the identification of individuals with acromegaly also
results in the identification of subjects predisposed to developing cancer

10 Endocrinology, 4th Ed., DeGroot and Jameson, 304 (2001) (“DeGroot”).
Appeal 2020-002584
Application 13/643,673

20
because, as disclosed in DeGroot, individuals with acromegaly are
predisposed to a number of diseases, including cancer. See DeGroot 304,
Table 22-6. Similarly, Trainer discloses all of the steps of claim 20 and,
therefore, anticipates this claim.
For the reasons described herein and those already of record, we
sustain the Examiner’s rejection of independent claims 8 and 20 as being
anticipated by Trainer. Claims 10–13, 15, 25–26, and 39 are not argued
separately, and, therefore, fall with claims 8 and 20. See 37 C.F.R.
§ 41.37(c)(1)(iv).
CONCLUSION
For the reasons described herein and those already of record, we
affirm the Examiner’s rejection of claims 1–3, 5, 8–15, 17, 20–26, and 31–
39.

DECISION SUMMARY
In summary:
Claims
Rejected
35 U.S.C.
§
Reference(s)/Basis Affirmed Reversed
1–3, 5, 8–15,
17, 20–26,
31–39
112(a) Enablement 1–3, 5, 8–15,
17, 20–26,
31–39

8, 10–13, 15,
20, 25, 26,
39
102(b) Trainer 8, 10–13, 15,
20, 25, 26,
39

Overall
Outcome
1–3, 5, 8–15,
17, 20–26,
31–39

Appeal 2020-002584
Application 13/643,673

21
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