Wisconsin Alumni Research Foundation

Patent Trials and Appeals Board

Aug 3, 2021

2020006751 (P.T.A.B. Aug. 3, 2021)

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.
15/723,826 10/03/2017 Joshua David Mezrich 960296.02170.P110206US04 4021
27114 7590 08/03/2021
WARF/MKE/QUARLES & BRADY LLP
ATTN: IP DOCKET
411 E. WISCONSIN AVENUE
SUITE 2400
MILWAUKEE, WI 53202-4428
EXAMINER
DILLAHUNT, SANDRA E
ART UNIT PAPER NUMBER
1646
NOTIFICATION DATE DELIVERY MODE
08/03/2021 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):
pat-dept@quarles.com
PTOL-90A (Rev. 04/07)

UNITED STATES PATENT AND TRADEMARK OFFICE
_________________

BEFORE THE PATENT TRIAL AND APPEAL BOARD
_________________

Ex parte JOSHUA DAVID MEZRICH and
CHRISTOPHER A. BRADFIELD

_________________

Appeal 2020-006751
Application 15/723,826
Technology Center 1600
_________________

Before DEBORAH KATZ, TAWEN CHANG, and
TIMOTHY G. MAJORS, Administrative Patent Judges.

KATZ, Administrative Patent Judge.

DECISION ON APPEAL
Appellant1 seeks our review,2 under 35 U.S.C. § 134(a), of the
Examiner’s decision to reject claims 12–19, 21–23, 33–37, 39, 40, 42, 43,

1 We use the word “Appellant” as defined in 37 C.F.R. § 1.42. Appellant
identifies the real party-in-interest as Wisconsin Alumni Research
Foundation. (Appeal Br. 3.)
2 We consider the Final Office Action issued May 3, 2019 (“Final Act.”), the
Appeal Brief filed December 27, 2019 (“Appeal Br.”) and the Examiner’s
Answer issued on May 1, 2020 (“Ans.”) in reaching our decision.
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and 45–48. We have jurisdiction under 35 U.S.C. § 6(b). We AFFIRM IN
PART and enter NEW GROUNDS OF REJECTION.
The Examiner made the following rejections of the claims:
Claims Grounds Citation in
Answer
12–19, 21–23, 33–37,
39, 40, 42, 43, 45–48
35 U.S.C. § 112 - written
description
3–9
12–19, 21–23, 33–37,
39, 40, 42, 43, 45–48
35 U.S.C. § 112 -
enablement
9–13
12, 15–19, 33, 34, 40,
42, 43, 45–48
35 U.S.C. § 102(b) over
Briscoe3
13–15
12, 15–19, 22, 23, 33,
34, 40, 42, 43, 45–48
35 U.S.C. § 103(a) over
Briscoe and Lara4
15–19

Appellant’s Specification is directed to using the compound SU5416
to treat patients with an autoimmune disease or inflammatory disorders.
(Spec. ¶ 6.) SU5416 was previously known to inhibit the vascular
endothelial growth factor (“VEGF”) receptor 2. (See id. ¶ 34.) The
inventors reportedly found that SU5416 also inhibits the aryl hydrocarbon
receptor (“AHR”), which promotes regulatory T-cells. (See id. ¶ 35.)
Appellant’s claims are directed to using SU5416 to reduce the differentiation
of Th17, a subset of T cells that produce the cytokine IL-17A, in order to
treat organ transplant rejection. (See Cunnusamy, 2.)

3 Briscoe, WO 2005/041877 A2, published May 12, 2005.
4 Primo N. Lara, Jr. et al., “SU5416 Plus Interferon α in Advanced Renal
Cell Carcinoma: A Phase II California Cancer Consortium Study with
Biological and Imaging Correlates of Angiogenesis Inhibition,” CLIN.
CANCER RES. 9:4772–81 (2003).
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Appellant’s claim 12 recites:
A method of treating a transplant patient in need of
immunosuppression by enhancing regulatory T cell generation
and reducing Th17 cell differentiation comprising the step of
(a) treating a transplant patient in need of
immunosuppression with an effective amount of SU5416,
wherein at least one symptom of transplant rejection is
reduced or alleviated, and wherein the effective amount of
SU5416 is sufficient to enhance regulatory T cell generation
and reduce Th17 cell differentiation in the patient.

(Appeal Br. 24.) Independent claim 34 also includes one active step of
treating the transplant patient in need of immunosuppression with an
effective amount of SU5416. (See id. 25.) Appellant does not address any
differences between independent claim 12 and independent claim 34 in
regard to the pending rejections.
35 U.S.C. § 112, first paragraph – written description
The Examiner rejects Appellant’s pending claims under 35 U.S.C.
§ 112, first paragraph, finding that their full scope is not described by the
Specification as filed. (See Ans. 3–9.)
The test for written description under 35 U.S.C. § 112, first paragraph,
is “whether the disclosure of the application relied upon reasonably conveys
to those skilled in the art that the inventor had possession of the claimed
subject matter as of the filing date.” Ariad Pharm., Inc. v. Eli Lilly & Co.,
598 F.3d 1336, 1351 (Fed. Cir. 2010). There is no requirement that the
disclosure contain either examples or an actual reduction to practice. Rather,
the critical inquiry is whether the patentee has provided a description that “in
a definite way identifies the claimed invention” in sufficient detail that a
person of ordinary skill would understand the inventor invented the full
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scope of what is claimed. See id. at 1352. “A ‘mere wish or plan’ for
obtaining the claimed invention is not adequate written description.”
Centocor Ortho Biotech, Inc. v. Abbott Labs., 636 F.3d 1341, 1348 (Fed.
Cir. 2011).
The Examiner finds that a method of treating a skin transplant patient
in need of immunosuppression by treating the patient with an effective
amount of SU5416 is described in the Specification because the results of
mouse skin transplant studies are provided. (Ans. 4; see Spec. ¶ 112, Figs.
11, 12.) But the Examiner determines that “the claims encompass far more
than treating a skin transplant patient,” including lung, heart, kidney, liver,
pancreas, corneal, and bronchiolitis-obliterans syndrome (“BOS”)
transplants. (Ans. 4.) The Examiner finds that the full scope of Appellant’s
claims are not sufficiently described in the Specification.
We begin by determining the broadest reasonable interpretation of
Appellant’s claims to determine what types of transplants are encompassed.
See In re Cortright, 165 F.3d 1353, 1358 (Fed. Cir. 1999) (“Although the
PTO must give claims their broadest reasonable interpretation, this
interpretation must be consistent with the one that those skilled in the art
would reach.”). Claims 12 and 34 recite “treating a transplant patient in
need of immunosuppression . . . .” (Appeal Br. 24, 25.) The Examiner
includes corneal transplant patients as being within the scope of Appellant’s
claims.
The Examiner determines that “[t]he specification teaches that the
solid transplants encompass corneal transplant, and thus, this type of
transplant is interpreted to be encompassed by the term transplant.” (Ans.
21.) We agree that the Appellant’s Specification states: “The SU5416
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treatment disclosed herein can be used to treat transplant rejection in a
number of solid organ transplants including, but not limited to, lung
transplants, skin transplants, cases of bronchiolitis-obliterans syndrome
(BOS), heart transplants, liver transplants, kidney transplants, pancreas
transplants, and corneal transplants.” (Spec. ¶ 69.) However, the language
of Appellant’s claims are more limited.
Specifically, as Appellant seems to argue, corneal transplants are not
encompassed within the scope of the currently pending claims because the
recited transplant patient must be “in need of immunosuppression.” (See
Appeal Br. 13.) Appellant argues that the eye is an immunoprivileged site
not requiring immunosuppression. (See id.) Appellant argues further that
cornea is a tissue without blood vessels making it significantly different
from solid functioning organs because transplants of these other organs must
actively interact with the circulating blood system of the recipient. (See id.,
citing Mezrich Decl. ¶ 15.)
Appellant’s arguments are supported by a publication, Cunnusamy,5
cited by the Examiner as evidence of the state of the art regarding the role of
Th17 and regulatory T cells (“Tregs”) in transplantation. (See Ans. 7.)
Cunnusamy teaches that IL-17A creates an immune privilege in corneal
transplants. (Cunnusamy Abstr.; see Ans. 7.) Thus, we agree with
Appellant that a patient receiving a corneal transplant is not in need of
immunosuppression.

5 Cunnusamy, et al., “IL-17A-dependent CD4+CD25+ Tregs Promote
Immune Privilege of Corneal Allografts,” J. IMMUNOL. 186:6737–45 (2011).
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Because a patient receiving corneal transplants is not a “transplant
patient in need of immunosuppression,” the broadest reasonable
interpretation of Appellant’s claims are methods of treatment in a transplant
patient receiving transplanted tissues that prompt a need for
immunosuppression, which excludes a corneal transplant. We agree that
Appellant’s Specification must demonstrate the inventors were in possession
of treatment for patients receiving a transplant of lung, heart, kidney, liver,
pancreas, and BOS transplants, but we disagree that it must show possession
of a treatment of patients receiving a corneal transplant. (See Ans. 4.)
Turning to the Examiner’s argument that the full scope of Appellant’s
claimed methods are not described because experiments with only skin
transplant models were presented, we review the evidence cited. First, the
Examiner cites Briscoe as evidence of the state of the art in treating
transplant recipients. (See Ans. 6–7.) Briscoe teaches administering a
VEGF antagonist with an immunosuppressing agent to inhibit graft rejection
in transplant patients. (See Briscoe ¶¶ 57, 61; see Ans. 6.) Briscoe teaches
administering a VEGF antagonist to inhibit rejection for a range of solid
organ transplants, including kidney, liver, lung, heart-lung, pancreas, bowel,
and heart. (See Briscoe claim 4; see Ans. 7.) Corneal transplants are not
included in the portions of Briscoe cited by the Examiner.
Instead of demonstrating that one of ordinary skill would have
considered the actions of VEGF antagonists to be unpredictable in inhibiting
rejection in a range of organ transplants, Briscoe tends to demonstrate the
opposite because it does not distinguish between rejection of transplants of
several different non-corneal organs. The Examiner does not cite to a
teaching in Briscoe that indicates treatment of skin transplants would react
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any differently than other organ transplants when the patient is treated with
VEGF antagonists. Thus, Briscoe does not support the Examiner’s
determination of the unpredictability of the effects of SU5416 on different
rejection of non-corneal organ transplants.
The Examiner also cites Cunnusamy as evidence of the state of the art
regarding the role of Th17 and Tregs in transplants. (See Ans. 7.) As
discussed above, Cunnusamy teaches that blocking IL-17A increases
rejection in corneal transplants, whereas it could be helpful in treating
rejection of cardiac and renal transplants. (Cunnusamy Abstr.; see Ans. 7.)
Thus, Cunnusamy distinguishes between corneal transplants and transplants
of other organs. The Examiner does not direct us to a teaching in
Cunnusamy that distinguishes between skin transplants and other, non-
corneal transplants. Thus, Cunnusamy does not support the Examiner’s
determination of the unpredictability of the effects of SU5416 on rejection of
different organ transplants in patients in need of immunosuppression.
The Examiner cites Garber6 as evidence of the state of the art
regarding clinical use of SU5416. (See Ans. 7–8.) Garber teaches that
VEGF inhibitors block angiogenesis and, therefore are expected to work
well to arrest tumor growth. (See Garber 1067; see Ans. 7.) Garber teaches,
though, that “[d]espite impressive performances in animal models . . .
inhibitors are not performing nearly as well in humans, spelling the end for
several candidates and at least one company. In February, for example,
Pharmacia (Peapeck, NJ) abandoned SU5416, a small molecule inhibitor of

6 Garber, “Angiogenesis inhibitors suffer new setback,” NATURE BIOTECH.
20:1067–68 (2002).
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the VEGF receptor.” (Id.) Although Garber addresses SU5416 specifically,
it does so only in the context of inhibiting VEGF receptors and treating
tumors, not in the context of alleviating symptoms of transplant rejection.
The Examiner concludes that Garber “provides direct evidence that
one cannot determine the efficacy of SU5416 in a particular disease based
upon preclinical studies demonstrating that the agent inhibits a particular
target.” (Ans. 21.) Although this may be true, it does not persuasively
support the Examiner’s assertion that results with a mouse skin transplant
model are insufficient written description of a method of treating rejection of
other organ transplants.
The Examiner also cites Roscoe7 as providing an example that ability
to “treat[] multiple sclerosis with SU5416 . . . is not predicative of treating
all autoimmune diseases encompassed by the claims.” (Ans. 8.) Because
Appellant’s currently pending claims are not directed to treating
autoimmune diseases, we are not persuaded that Roscoe is evidence of how
one of ordinary skill in the art would understand whether the inventors were
in possession of the claimed methods. The Examiner does not explain how
Roscoe supports the finding that results reported in the Specification from
the mouse skin transplant model are not predictive of other organ
transplants.
The Examiner concludes that there are no generalized art recognized
models or assays that would allow one to determine if IL-17 is dysregulated
in a particular transplant or that would allow one of ordinary skill to predict

7 Roscoe et al., “VEGF and angiogenesis in acute and chronic MOG ((35–
55)) peptide induced EAE,” J. NEUROIMMUNOL. 209:6–15 (2009).
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that SU5416 would sufficiently inhibit IL-17 to treat all transplant patients.
(See Ans. 22.) None of the evidence cited by the Examiner expressly or
persuasively addresses this issue.
In opposition to the Examiner’s rejection, Appellant cites to
paragraphs 61 through 69 of the Specification, which provide for a range of
specific types of solid tissue transplantation. (See Appeal Br. 11.) Appellant
also points to the description of mouse skin transplants model experiments in
the examples of the Specification, arguing that those of ordinary skill would
have understood these results to demonstrate the claimed methods would be
successful with other types of transplants, including solid organ transplants.
(See id. at 12–13.) Appellant argues that the skin transplant model is “the
most stringent and generally accepted model for studying transplant
rejection” and is “the gold standard and . . . a widely accepted model for
studying compounds that prevent transplant rejection, including transplants
other than skin, including solid organ transplants.” (Id. at 11–13.) Thus,
according to Appellant, these results would have been applicable to other
“less stringent transplants.” (See id. at 12–13.)
To support this argument, Appellant relies on the declaration of
inventor Joshua Mezrich.8 (See Appeal Br. 11–12.) Dr. Mezrich testifies:
The skin transplant model used in the instant application is a
widely accepted model for treatment of transplant rejections in
the field. Skin grafts/transplants are the most stringent models
for studying transplant. Specifically, the mouse skin transplant
model is widely used to investigate immunological mechanisms
of graft chronic/acute rejection and use of immunosuppressive

8 Declaration of Joshua Mezrich, dated January 16, 2019.
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treatments, and thus a standard accepted model in the transplant
research community.

(Mezrich Decl. ¶ 9.) Dr. Mezrich states that the skin transplant model is still
used as a model for immune responses in transplantation, citing Medawar9
and Feng.10 (See id. ¶ 10.)
Although these publications rely on skin transplant models, neither
Dr. Mezrich nor Appellant directs us to teachings in the publications
demonstrating such models would have lead one of ordinary skill in the art
to reasonably predict all other solid organ transplants in human patients
would also be successful. Dr. Mezrich merely cites to these publications,
stating that they demonstrate use of the skin transplant model. Without an
explanation of how they indicate a skilled artisan would have predicted
success with other solid organ transplants, it is not clear how these
publications support his testimony.
Appellant asserts that Dr. Mezrich testifies that the skin transplant
model is the “gold standard” for use in studying transplantation, but Dr.
Mezrich does not use this language in his declaration. (Appeal Br. 12.) Dr.
Mezrich does testify that the model is the “most stringent” (Mezrich Decl.
¶ 9), but it is unclear exactly what this means and how it relates to whether
success in a skin transplant model indicates reasonably predictable success
in transplants of other solid organs in humans.

9 Lance and Medawar, “Survival of Skin Heterografts Under Treatment with
Antilymphocyte Serum,” LANCET 1:1174–76 (1968).
10 Feng et al., “Functional Regulatory T Cells Produced by
Inhibiting Cyclic Nucleotide Phosphodiesterase Type 3 Prevent Allograft
Rejection,” SCI. TRANSL. MED. 3:1–10 (2011).
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Dr. Mezrich also testifies, citing to Deteix,11 Heidt,12 Fan,13 that it was
known IL-17 levels increase when liver and kidney transplants are being
rejected and that regulatory cells were known to play a role in lung
transplant rejection. (See Mezrich Decl. ¶ 11; see Appeal Br. 12.)
Dr. Mezrich testifies that in response, the claimed method activates the AHR
receptor to increase regulatory T cells and up-regulate Th17 cell
differentiation. (See Mezrich Decl. ¶ 12; see Appeal Br. 12.) Dr. Mezrich
testifies that in the current application the immune response to
transplantation is modulated by activating the AHR receptor, which
increases regulatory T cells and up-regulates Th17 cell differentiation. (See
Mezrich Decl. ¶¶ 11–12.) Dr. Mezrich states:
This mechanism would be suitable to be able to be applied by
one skilled in the art to the treatment of other transplants
besides skin transplants as in the examples as skin transplants
are the most difficult transplant rejections to treat. Thus, these
methods can be applied to solid organ transplants, for example
heart, liver and lung transplants which are known to be
characterized by up-regulation of Th17 cell differentiation. This
specific method of action of SU5416 allows for one skilled in

11 Deteix, et al., “Intragraft Th17 Infiltrate Promotes Lymphoid Neogenesis
and Hastens Clinical Chronic Rejection,” J. IMMUNOL., 184: 5344–51
(2010).
12 Heidt, et al., “The impact of TH17 cells on transplant rejection and the
induction of tolerance,” CURR. OPIN. ORGAN TRANSPLANT., 15:456–61
(2010).
13 Fan et al., “Neutralizing IL-17 Prevents Obliterative Bronchiolitis in
Murine Orthotropic Lung Transplantation,” AM. J. TRANSPLANT., 11:911–22
(2011).
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the art to treat a subject with a solid organ transplants without
undue experimentation.

(Mezrich Decl. ¶ 12.)
Although Deteix, Heidt, and Fan support Dr. Mezrich’s testimony
about the role of IL-17 in rejection of transplants of several different organs,
he does not cite to support for his assertion that skin transplants are the most
difficult transplant rejections to treat or that success in a mouse model of
skin transplants would allow one of ordinary skill to predict that the claimed
method would be successful in human transplants of other solid organ.
After reviewing the evidence presented by the Examiner and by
Appellant and considering that the Examiner carries the burden of showing
that Appellant’s claims are not patentable, we are not persuaded by the
Examiner’s rejection. See 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.”).
The Examiner finds that although the Specification demonstrates
SU5416 is a strong ligand of AHR, the Specification does not provide a
nexus between the ability of SU5416 to bind to AHR and the treatment of
the claimed conditions. (See Ans. 4.) We disagree because the Specification
provides data reportedly showing that in a skin transplant model, “mice that
received SU5416 had prolonged graft survival compared to the control
group.” (Spec. ¶ 112; see also Figs. 11, 12.) Although we are not entirely
convinced by Appellant’s evidence that one of ordinary skill in the art would
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have predicted the same results with other organ transplants, it is the
Examiner’s burden to present persuasive evidence to the contrary. The
Examiner fails to do so.
For example, the Examiner directs us to Briscoe, which teaches a
method of inhibiting rejection in a recipient comprising administering a
VEGF antagonist can be used for several different organ transplants,
including kidney, liver, lung, heart-lung, pancreas, bowel, and heart.
Briscoe tends to indicate one of ordinary skill would have considered there
to be no difference between several different organ transplants. Cunnusamy
does differentiate between corneal transplants and other organs, but
Appellant’s claims exclude methods of treating patients who receive corneal
transplants. Garber distinguishes between preclinical studies and human
studies, but does not address using SU5416 to treat transplant rejection and
does not address different rejection effects in different transplanted organs.
In contrast, the declaration and supporting evidence presented by
Appellant indicate that the mouse skin transplant model was accepted by
those in the art for evaluation of treatments for transplant rejection.
Although Appellant’s evidence does not directly address the issue of
whether a skin transplant model was considered to be predictive of other
organ transplants, it demonstrates that the mouse skin model would have
allowed one of ordinary skill to predict the effectiveness of a treatment to
some degree. Given that the Examiner fails to present sufficiently
persuasive evidence that one of ordinary skill would have considered the
mouse skin transplant model to not be informative for other organ
transplants in patients in need of immunosuppression, the balance of the
evidence does not support the Examiner’s rejection. The balance of the
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evidence on this record does not persuade us that one of ordinary skill in the
art would not have reasonably believed the inventors to be in possession of
the full scope of the claimed method.
Accordingly, we reverse the Examiner’s rejection for lack of written
description under 35 U.S.C. § 112, first paragraph.

35 U.S.C. § 112, first paragraph – enablement
The Examiner also rejected Appellant’s claims as lacking an enabling
disclosure under 35 U.S.C. § 112, first paragraph. (See Ans. 9–13.)
To determine if subject matter is enabled, we ask whether it would
have required undue experimentation to make and use it. See In re Wands,
858 F.2d 731, 736–37 (Fed. Cir. 1988); see also Johns Hopkins Univ. v.
CellPro, Inc., 152 F.3d 1342, 1360 (Fed. Cir. 1998). Factors to be
considered in determining whether a disclosure would require undue
experimentation include:
(1) the quantity of experimentation necessary, (2) the amount of
direction or guidance presented, (3) the presence or absence of
working examples, (4) the nature of the invention, (5) the state
of the prior art, (6) the relative skill of those in the art, (7) the
predictability or unpredictability of the art, and (8) the breadth
of the claims.
Wands, 858 F.2d at 736–37.
The Examiner raises many of the same issues raised for the rejection
based on lack of written description. For example, the Examiner finds that
Appellant’s Specification fails to demonstrate a correlation between the
structure of SU5416 and its function. (See Ans. 9–10.) The Examiner finds
that although the state of the art is “relatively high with regard to treating
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individual transplants,” there is no known agent that is effective in treating
all transplant recipients and that transplant treatment arts have a high level of
unpredictability. (See id. at 10.) According to the Examiner, the alleged
lack of guidance in the Specification to treating all types of transplants with
SU5416 makes the claimed methods unpredictable. (See id.)
The Examiner cites Briscoe, Cunnusamy, Garber, and Roscoe to
support these findings, but as explained above, we are not persuaded that
they demonstrate one of ordinary skill in the art would have considered
treatment of transplant rejection of any organ to be unpredictable given the
successful results with the skin transplant model presented in the
Specification. Thus, in light of the guidance provided in the Specification
and the high level of skill demonstrated in the prior art, we are not persuaded
on this record that practicing Appellant’s claimed methods would have
required undue experimentation.
Accordingly, we reverse the Examiner’s rejection for lack of an
enabling disclosure under 35 U.S.C. § 112, first paragraph.

35 U.S.C. § 102(b)
The Examiner rejects claims 12, 15–19, 33, 34, 40, 42, 43, and 45–48
under 35 U.S.C. § 102(b) over Briscoe. (See Ans. 13–15.) Appellant does
not argue separately for the patentability of any of the rejected claims.
Accordingly, we again focus on claim 12 in our review. See 37 C.F.R.
§ 41.37(c)(1)(iv).
Briscoe teaches treating a transplant patient to prevent rejection by
administering an effective amount of a VEGF antagonist. (See Briscoe ¶ 8;
see Ans. 13.) Briscoe includes SU5416 as one of four recited VEGF
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inhibitors. (See Briscoe ¶ 15; see Ans. 13.) Briscoe teaches that the VEGF
antagonist can be administered with an immunosuppressive agent to reduce
the dose of the immunosuppressive agent. (See Briscoe ¶¶ 57, 61.) The
claims of Briscoe recite methods of inhibiting rejection of several solid
organs, including kidney, liver, lung, heart-lung, pancreas, bowel, heart, or
skin, by administering a VEGF antagonist. (See Briscoe ¶ 77, claim 4.)
Thus, the Examiner finds that Briscoe teaches treating a transplant patient in
need of immunosuppression with SU5416.
Appellant argues that one of ordinary skill would not have assumed
from the teachings of Briscoe that VEGF antagonists are ligands for AHR or
that the four VEGF antagonists taught in Briscoe would be able to activate
AHR. (See Appeal Br. 18.) We are not persuaded by this argument because
we agree with the Examiner that SU5416 is inherently a ligand for AHR.
Furthermore, we agree with the Examiner that the only recited active step is
“treating a transplant patient in need of immunosuppression with an
effective amount of SU5416.” (Appeal Br. 24; see Ans. 14.) Thus, because
Briscoe teaches using SU5416 to treat transplant patients in need of
immunosuppression, it anticipates Appellant’s claimed method.
The phrases in claim 12 “wherein at least one symptom of transplant
rejection is reduced or alleviated” and “wherein the effective amount of
SU5416 is sufficient to enhance regulatory T cell generation and reduce
Th17 cell differentiation in the patient” are not active steps and do not limit
the sole active step. Instead, as the Examiner explains, these limitations
express the intended results of the active step – specifically, relief or
reduction of at least one symptom of transplant rejection, enhanced
regulatory T cell generation, and reduction in Th17 cell differentiation in the
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patient. (See Ans. 14.) The Examiner finds that these results are inherent
properties of the recited active step of treating with SU5416 because they
necessarily occur. (See id.) Appellant does not direct us to evidence to the
contrary, such as showing that the recited effects do not always occur when
a patient is treated with an amount of SU5416 disclosed in the prior art.
Appellant argues further that the claimed method is based on the
surprising discovery that ligands for AHR, including SU5416
immunomodulate the differentiation of T cells toward a regulatory pathway
rather than the Th17 pathway for the treatment of transplant patients. (See
Appeal Br. 18.) We are not persuaded by this argument because “a prior art
reference may anticipate without disclosing a feature of the claimed
invention if that missing characteristic is necessarily present, or inherent, in
the single anticipating reference.” Schering Corp. v. Geneva Pharm., 339
F.3d 1373, 1377 (Fed. Cir. 2003). We agree with the Examiner that “the
discovery of a previously unappreciated property of a prior art composition,
or of a scientific explanation for the prior art’s functioning, does not render
the old composition patentably new to the discoverer.” Atlas Powder Co. v.
lreco, Inc., 190 F.3d 1342, 1347 (Fed. Cir. 1999). (See Ans. 14.) The
inherent nature of the inventors’ discovery (even assuming they were the
first to discover it) renders the claimed method anticipated by Briscoe.
Appellant cites to Dr. Mezrich’s testimony to argue that VEGF
antagonists were not normally used by transplant physicians because they
would not want to inhibit angiogenesis in a newly transplanted organ. (See
Appeal Br. 18–19; see Mezrich Decl. ¶ 6.) This argument is not persuasive
because Briscoe expressly teaches treating transplant patients with SU5416,
which is a VEGF antagonist. (See Briscoe ¶ 57 (“A further benefit of co-
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administration of a VEGF antagonist/anti-VEGF antibody and an
immunosuppressive agent is that the dose of immunosuppressive agent
required to inhibit graft rejection can be reduced to subtherapeutic levels
(e.g., a dose that does not inhibit graft rejection when administered as the
sole therapeutic agent).”).)
We are also not persuaded by Appellant’s argument that Briscoe does
not anticipate because it does not provide working examples or data showing
that SU5416 treats transplant patients by targeting AHR to enhance
regulatory T cells and reducing Th17 cell differentiation. (See Appeal Br.
19.) Briscoe expressly teaches treating a transplant patient with SU5416 and
Appellant does not direct us to evidence that Briscoe fails to describe or
enable this step.
Because we are not persuaded by Appellant’s arguments, we are not
persuaded that the Examiner erred in rejecting claims 12, 15–19, 33, 34, 40,
42, 43, and 45–48 as being anticipated by Briscoe. Accordingly, we affirm
the Examiner’s rejection under 35 U.S.C. § 102(b) over Briscoe.

35 U.S.C. § 103(a)
The Examiner rejects Appellant’s claims 12, 15–19, 22, 23, 33, 34,
40, 42, 43, and 45–48 as being obvious under 35 U.S.C. § 103(a) over
Briscoe and Lara. (See Ans. 15–19.) The Examiner finds that Briscoe
teaches an effective dose of VEGF antagonist can range from 0.1 mg per day
to about 100 mg/day for an adult. (See Ans. 16; see Briscoe ¶¶ 62–64.) The
Examiner cites Lara for its teaching that the maximum tolerated dose of
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Application 15/723,826

19
SU5416 in humans is 145 mg/m2, intravenously twice weekly. (See Lara
4773; see Ans. 17.)
The Examiner finds that Appellant’s claims reciting the amount of
SU5416 in the treatment as 30–150 mg/m2 (claim 22) and 85–145 mg/m2
(claim 23) would have been obvious from the teachings of Briscoe of a
range encompassing the claimed ranges and from the teaching of Lara of the
maximum dose at the upper end of the claimed ranges. (See Ans. 17–18,
citing In re Aller, 220 F.2d 454, 456 (CCPA 1955) (“Normally, it is to be
expected that a change in temperature, or in concentration, or in both, would
be an unpatentable modification.”).)
Appellant argues only that Lara does not cure the alleged deficiencies
of Briscoe asserted in response to the Examiner’s rejection under 35 U.S.C.
§ 103(a). (See Appeal Br. 20–22.)
Because we determined there were no deficiencies in the Examiner’s
rejection over Briscoe alone, we are not persuaded that the Examiner erred
in rejecting the recited claims over Briscoe and Lara as being obvious.
Accordingly, we affirm the Examiner’s rejection under 35 U.S.C. § 103(a).
New Grounds of Rejection
The Examiner did not reject claims 13, 14, 21, 35–37, or 39 over the
prior art under 35 U.S.C. § 102 or § 103. We enter new grounds of rejection
for each of these claims based on the teachings of Briscoe and Lara.
Claim 13 recites “[t]he method of claim 12, wherein the patient is
treated when at least one symptoms [sic] of the transplant rejection is
diagnosed.” (See Appeal Br. 24.) Because Briscoe teaches inhibiting
(reducing or preventing) graft rejection by administering a VEGF antagonist
such as SU5416, Briscoe teaches treating a symptom of transplant rejection
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Application 15/723,826

20
that has been diagnosed. (See Briscoe ¶¶ 56–57.) Accordingly, we enter a
new grounds of rejection for claim 13 under 35 U.S.C. § 102(b) over
Briscoe.
Claim 14 recites: “[t]he method of claim 13, wherein the symptom is
at acute phase.” (Appeal Br. 24.) Claim 39 recites: “[t]he method of claim
34, wherein the patient has had acute and chronic rejection episodes.”
(Appeal Br. 25.) Briscoe defines “inhibiting rejection” in the methods it
teaches as including treatment or preventing either acute or chronic graft
rejection. (See Briscoe ¶ 12.) Accordingly, we enter a new grounds of
rejection for claims 14 and 39 under 35 U.S.C. § 102(b) over Briscoe.
Claims 21 and 35 recite the methods of claims 12 and 34,
respectively, “wherein the patient are treated for a few weeks to months.”
(Appeal Br. 25.) Briscoe teaches that antibody or antigen-binding fragment
VEGF inhibitors can be administered daily, weekly, bi-weekly, monthly, or
less frequently. (See Briscoe ¶ 65.) Because SU5416 is considered by
Briscoe to be an alternative to antibody VEGF inhibitors, treatment for a few
weeks to months with SU5416 would have been obvious. (See id. ¶¶ 14–
15.) Accordingly, we enter a new grounds of rejection for claims 21 and 35
under 35 U.S.C. § 103(a) over Briscoe.
Claim 36 recites: “[t]he method of claim 34, wherein the amount of
SU5416 in the treatment is 30-150 mg/m2.” (Appeal Br. 25.) Claim 37
recites: “[t]he method of claim 34, wherein the amount of SU5416 in the
treatment is 85-145 mg/m2.” (Appeal Br. 25.) Given the teachings in
Briscoe and Lara regarding dosing of VEGF antagonists as explained in the
Examiner’s rejection (see Ans. 17–18), and the normal expectation that
changes in concentration are not patentable modifications (see Aller, supra),
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21
we enter a new grounds of rejection for claims 36 and 37 under 35 U.S.C.
§ 103(a) over Briscoe and Lara.
CONCLUSION
Upon consideration of the record and for the reasons given, we affirm
in part the Examiner’s rejection and enter new grounds of rejection.
In summary:
Claim(s)
Rejected
35 U.S.C.
§
Reference(s)/
Basis
Affirmed Reversed New
Grounds
12–19,
21–23,
33–37, 39,
40, 42, 43,
45–48
112(a) Written
Description
12–19,
21–23,
33–37,
39, 40,
42, 43,
45–48

12–19,
21–23,
33–37, 39,
40, 42, 43,
45–48
112(a) Enablement 12–19,
21–23,
33–37,
39, 40,
42, 43,
45–48

12, 15–19,
33, 34, 40,
42, 43,
45–48
102(b) Briscoe 12, 15–
19, 33,
34, 40,
42, 43,
45–48

12, 15–19,
22, 23, 33,
34, 40, 42,
43, 45–48
103(a) Briscoe, Lara 12, 15–
19, 22,
23, 33,
34, 40,
42, 43,
45–48

13, 14, 39 102(b) Briscoe 13, 14, 39
21, 35 103(a) Briscoe 21, 35
36, 37 103(a) Briscoe, Lara 36, 37
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Overall
Outcome
12, 15–
19, 22,
23, 33,
34, 40,
42, 43,
45–48
13, 14,
21, 35–
37, 39
13, 14,
21, 35–
37, 39

We entered a new ground of rejection for claims 13, 14, 21, 35–37,
and 39 pursuant to 37 C.F.R. § 41.50(b). 37 C.F.R. § 41.50(b) provides that
“[a] new ground of rejection . . . shall not be considered final for judicial
review.” 37 C.F.R. § 41.50(b) also provides that Appellant:
WITHIN TWO MONTHS FROM THE DATE OF THE
DECISION, must exercise one of the following two
options with respect to the new ground of rejection to
avoid termination of the appeal as to the rejected claims:

(1) Reopen prosecution. Submit an appropriate
amendment of the claims so rejected or new Evidence
relating to the claims so rejected, or both, and have the
matter reconsidered by the examiner, in which event the
prosecution will be remanded to the examiner . . . .

(2) Request rehearing. Request that the proceeding be
reheard under § 41.52 by the Board upon the same record
. . . .

AFFIRMED IN PART; 37 C.F.R. § 41.50(b)