FRED HUTCHINSON CANCER RESEARCH CENTER

Patent Trials and Appeals Board

Dec 11, 2020

2020001970 (P.T.A.B. Dec. 11, 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.
14/701,779 05/01/2015 Thomas SPIES F053-0111USC3 8096
29150 7590 12/11/2020
LEE & HAYES, P.C.
601 W. RIVERSIDE AVENUE
SUITE 1400
SPOKANE, WA 99201
EXAMINER
SKELDING, ZACHARY S
ART UNIT PAPER NUMBER
1644
NOTIFICATION DATE DELIVERY MODE
12/11/2020 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):
lhpto@leehayes.com
PTOL-90A (Rev. 04/07)

UNITED STATES PATENT AND TRADEMARK OFFICE
____________

BEFORE THE PATENT TRIAL AND APPEAL BOARD
____________

Ex parte THOMAS SPIES and VERONIKA SPIES
____________

Appeal 2020-001970
Application 14/701,779
Technology Center 1600
____________

Before JEFFREY N. FREDMAN, DEBORAH KATZ, and
JOHN G. NEW, Administrative Patent Judges.

FREDMAN, Administrative Patent Judge.

DECISION ON APPEAL
This is an appeal1,2 under 35 U.S.C. § 134(a) involving claims to a
method of treating Crohn’s Disease. The Examiner rejected the claims as
anticipated, obvious, lacking enablement, and lacking written description.
We have jurisdiction under 35 U.S.C. § 6(b). We affirm.

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 Fred
Hutchinson Cancer Research Center (see Appeal Br. 1).
2 We have considered and herein refer to the Specification of Dec. 2, 2016
(“Spec.”); Final Office Action of Mar. 19, 2019 (“Final Act.”); Appeal Brief
of Aug. 16, 2019 (“Br.”); and Examiner’s Answer of Oct. 23, 2019 (“Ans.”).
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Statement of the Case
Background
NKG2D is an activating receptor expressed on most natural killer
(“NK”) cells, CD8 T cells, and other T cells (Spec. ¶ 4). “Ligand
engagement of NKG2D activates NK cells and potently co-stimulates
effector T cells” (id). “Because ligand binding unconditionally triggers
NKG2D, its dysregulation together with anomalous expression of MIC
[Major histocompatibility complex (“MHC”) class I chain related
molecules] in local tissue environments could promote autoreactive T cell
stimulation effector T cells” (id.). Antibodies “specifically targeting and/or
inhibiting the NKG2D receptor on immune cells such as T cells, e.g., CD4+
T cells, in patients . . . can limit the pathological effects of cells expressing
the NKG2D receptor, e.g., by interfering with the activation of the cells” (id.
¶ 7). NKG2D may be inhibited by compounds that: (1) “inhibit the
activation of NKG2D by a ligand,” (2) “act antagonistically in the absence
of a ligand to decrease the activity of the receptor,” (3) “decrease the
expression level of the receptor,” (4) “block NKG2D-triggered signaling or
gene expression,” (5) “block any other activity of the cell that results from
NKG2D activation” (id. ¶ 28).
The Claims
Claims 1, 3–5, 8–10, 12, 13 and 35–38 are on appeal. Independent
claim 1 is representative and reads as follows:
1. A method of treating a human patient with Crohn’s Disease,
said method comprising administering to said patient a
pharmaceutical composition comprising a blocking anti-
NKG2D monoclonal antibody and a pharmaceutically
acceptable carrier.

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The Rejections
A. The Examiner rejected claims 1, 3, 9, and 10 under 35 U.S.C. § 102(a)
as anticipated by Cosman3 as evidenced by Allez4 (Ans. 3–8).
B. The Examiner rejected claims 1, 3, 9, and 10 under 35 U.S.C. § 103(a)
as obvious over Cosman and Taub,5 as evidenced by Sutherland6 (Ans. 8–
21).
C. The Examiner rejected claims 1, 3, 4, 5, 9, 10, and 37 under 35 U.S.C.
§ 103(a) as obvious over Cosman, Taub, the Spies Declaration,7 and Bauer,8
as evidenced by Sutherland (Ans. 21–28).
D. The Examiner rejected claims 1 and 8 under 35 U.S.C. § 103(a) as
obvious over Cosman, Deventer,9 and Strom10 (Ans. 28).

3 Cosman, WO 03/029436 A2, published Apr. 10, 2003.
4 Allez et al., CD4+NKG2D+ T Cells in Crohn’s Disease Mediate
Inflammatory and Cytotoxic Responses Through MICA Interactions, 132
Gastroenterology 2346–2358 (2007).
5 Taub et al., Functional Validation of Ligand Mimicry by Anti-Receptor
Antibodies: Structural and Therapeutic Implications, 31 Biochemistry
7431–7435 (1992).
6 Sutherland et al., UL16-Binding Proteins, Novel MHC Class I-Related
Proteins, Bind to NKG2D and Activate Multiple Signaling Pathways in
Primary NK Cells, 168 J. Immunology 671–679 (2002).
7 Declaration of Veronika Groh Spies, M.D. dated June 12, 2018.
8 Bauer et al., Activation of NK Cells and T Cells by NKG2D, a Receptor for
Stress-Inducible MICA, 285 Science 727–729 (1999).
9 Deventer, New biological therapies in inflammatory bowel disease, 17 Best
Practice & Res. Clin. Gastroenterology 119–130 (2003).
10 Strom et al., Therapeutic Immunology, K. Frank Austen ed., Blackwell
Science Inc. 451–456 (1996).
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E. The Examiner rejected claims 1 and 35 under 35 U.S.C. § 103(a) as
obvious over Cosman, and Humira11 (Ans. 28).
F. The Examiner rejected claims 1 and 36 under 35 U.S.C. § 103(a) as
obvious over Cosman, Taub, and Melief,12 as evidenced by Sutherland and
Jamieson13 (Ans. 28–29).
G. The Examiner rejected claims 1, 36, and 38 under 35 U.S.C. § 103(a)
as obvious over Cosman, Taub, the Spies Decl., Melief, and Humira, as
evidenced by Sutherland and Jamieson (Ans. 29)
H. The Examiner rejected claim 8 under 35 U.S.C. § 112, first paragraph,
as lacking enablement (Ans. 30–32).14
I. The Examiner rejected claims 12 and 13 under 35 U.S.C. § 112,
second paragraph, as being indefinite (Ans. 29–30).15

A. 35 U.S.C. § 102 over Cosman
The Examiner finds Cosman teaches producing monoclonal anti-
idiotypic antibodies that bind to NKG2D and may block or inhibit activation
of immune effector cells via NKG2D (Ans. 3). The Examiner finds Cosman

11 Spondylitis Assoc. of America., Abbott Laboratories receives FDA
approval earlier than anticipated for HUMIRATM (Adalimumab) for the
treatment of Rheumatoid Arthritis (RA) (2003), http://stopas.com/press/
news/045.aspx
12 Melief et al., US 200/0022860 A1, published Jan. 30, 2003.
13 Jamieson et al., The Role of the NKG2D Immunoreceptor in Immune Cell
Activation and Natural Killing, 17 Immunity 19–29 (2002).
14 The Examiner withdrew the rejection of claim 1 under 35 U.S.C. § 112,
first paragraph as lacking enablement (Ans. 3).
15 Appellant does not respond to the Examiner’s rejection of claims 12 and
13 for being indefinite. Accordingly, we summarily affirm the rejection.
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teaches treating Crohn’s Disease by administering anti-idiotypic antibodies
that bind NKG2D and block or inhibit activation via NKG2D (id. at 4).
The issue with respect to this rejection is: Does a preponderance of
the evidence of record support the Examiner’s conclusion that Cosman
discloses treating Crohn’s Disease by administering a blocking anti-NKG2D
monoclonal antibody?
Findings of Fact (“FF”)
1. Cosman discloses UL16 binding protein (“ULBP”)-4 that binds
to NKG2D and has “the capacity to activate immune effector cells, including
NK cells and T cells, expressing NKG2D” (Cosman p. 3).
2. Cosman discloses anti-ULBP4 antibodies that can: (1) bind to
ULBP polypeptides; (2) be human or humanized; (3) prevent or inhibit
activation of NKG2D expressing cells by the interaction of a ULBP protein
and NKG2D; or (4) inhibit the binding of ULBP protein to NKG2D
(Cosman p. 4).
3. Cosman discloses “antibodies to the ULBP polypeptide can, in
turn, be utilized to generate anti-idiotype antibodies that ‘mimic’ the ULBP
polypeptide and that may bind to the ULBP polypeptide’s binding partners
using techniques well known to those skilled in the art” (Cosman p. 22).
4. Cosman discloses “such anti-idiotype antibodies can, for
example, bind to NKG2D and may or may not activate immune effector
cells expressing NKG2D. Thus such antibodies may activate NKG2D-
expressing immune effector cells, including NK cells, T cells, and/or
macrophages, or may block or inhibit activation of such cells via NKG2D”
(Cosman p. 22).
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5. Cosman discloses treating “diseases characterized by
inappropriate inflammation, such as inflammatory bowel disease and
Crohn’s disease,” by administering “an anti-idiotypic antibody that can
block or inhibit activation via NKG2D” (Cosman p. 36).
6. Cosman discloses “an antagonistic anti-ULBP antibody or . . .
or anti-idiotypic antibody can be administered to a patient suffering from
inflammatory diseases, such as inflammatory bowel disease and Crohn's
disease, to decrease or eliminate the symptoms of these diseases” (Cosman
p. 37).
Principles of Law
Anticipation under 35 U.S.C. § 102 requires that “each and every
element as set forth in the claim is found, either expressly or inherently
described, in a single prior art reference.” In re Robertson, 169 F.3d 743,
745 (Fed. Cir. 1999).
Analysis
We adopt the Examiner’s findings of fact and conclusion of law (see
Ans. 3–8, FF 1–6) and agree that Cosman anticipates the claims. We
address Appellant’s arguments below.
Appellant contends “Cosman fails to teach the use of a blocking anti-
NKG2D antibody for the treatment of Crohn’s disease” (Br. 2). Appellant
contends that the claimed “anti-NKG2D antibody binds to NKG2D through
hypervariable region specificity” (id.). In contrast, Appellant contends that
Cosman’s anti-idiotypic antibody is not an anti-NKG2D antibody because it
specifically recognizes an idiotype with hypervariable region specificity and
not NKG2D (id.). Appellant acknowledges “one may envision an antibody
that mimics a ULBP polypeptide and binds to NKG2D in a similar manner
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as a ULBP polypeptide,” however, “anti-idiotype antibodies are still
antibodies whose hypervariable regions specifically recognize an idiotype of
another antibody, whereas anti-NKG2D antibodies are antibodies whose
hypervariable regions recognize NKG2D” (id. at 2–3).
We find that Appellant’s arguments fail from the outset because they
are not based on limitations appearing in the claims. See In re Self, 671 F.2d
1344, 1348 (CCPA 1982); see also In re Hyatt, 211 F.3d 1367, 1372 (Fed.
Cir. 2000)(“during examination proceedings, claims are given their broadest
reasonable interpretation consistent with the specification”). Claim 1 recites
administering “a blocking anti-NKG2D monoclonal antibody.” As the
Examiner pointed out
This phrase, given its broadest reasonable interpretation
consist[ent] with the teachings of the instant specification and
its plain meaning in the art would be understood to encompass
in its breadth administering any monoclonal antibody that binds
and antagonizes NKG2D, regardless of how said antibody is
made. Importantly, the skilled artisan would not consider the
antibodies of the claims to only encompass antibodies produced
subsequent to NKG2D immunization. Such a narrow
interpretation would be contrary to the teachings of the instant
specification.

(Ans. 5). Appellant does not point to any express definition in the
Specification that requires an antibody with hypervariable regions specific to
NKG2D (see generally Br.). Rather, the Specification broadly defines
antibodies as full length antibodies or antibody fragments and derivatives
that bind preferably to NKG2D in a competitive binding assay (Spec. ¶¶ 29,
30, 45).
Moreover, we agree with the Examiner that, “the anti-idiotypic
antibodies that bind NKG2D and block or inhibit activation via NKG2D
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described by Cosman would certainly be considered by the ordinarily skilled
artisan to be antibodies having hypervariable regions that recognize
NKG2D” in view of the general knowledge in the art illustrated by Taub
(Ans. 7–8). Our reviewing court has held that
where the Patent Office has reason to believe that a functional
limitation asserted to be critical for establishing novelty in the
claimed subject matter may, in fact, be an inherent
characteristic of the prior art, it possesses the authority to
require the applicant to prove that the subject matter shown to
be in the prior art does not possess the characteristic relied on.

In re Best, 562 F.2d 1252, 1254–55, (CCPA 1977).
Appellant has not provided evidence that Cosman’s anti-idiotypic
antibody that binds to NKG2D does not have hypervariable regions that
recognize NKG2D (see generally Br.). See Johnston v. IVAC Corp., 885
F.2d 1574, 1581 (Fed. Cir. 1989) (“Attorneys’ argument is no substitute for
evidence”). Accordingly, we are not persuaded that the Examiner erred.
Conclusion of Law
A preponderance of the evidence of record support the Examiner’s
conclusion that Cosman anticipates the claims.

B. 35. U.S.C. § 103(a) over Cosman and Taub, as evidenced by
Sutherland
The Examiner finds “Cosman does not explicitly teach a method
wherein said blocking antibody interferes with the binding of an NKG2D
ligand to the NKG2D receptor,” as recited by claim 5 (Ans. 8). The
Examiner finds “Taub teaches monoclonal anti-receptor antibodies that
compete with [a] ligand for receptor binding can be produced either by
isolating anti-receptor antibodies subsequent to immunization or by
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generating anti-idiotypic antibodies” (id.). The Examiner concludes it would
have been obvious to a person of ordinary skill in the art to treat Crohn’s
disease by administering an “antibody isolated from an animal immunized
with NKG2D” as an alternative to a receptor-binding anti-idiotypic antibody
(id. at 8–9).
The issue with respect to this rejection is: Does a preponderance of
the evidence of record support the Examiner’s conclusion that the
combination of Cosman and Taub renders the claims obvious?
Findings of Fact (“FF”)
7. Taub teaches “[a]nti-receptor antibodies have been prepared
either by isolating antibodies directed against the receptor or by generating
anti-idiotypic or autoanti-idiotypic antibodies” (Taub 7431).
8. Taub’s Figure 2 is reproduced below:

Taub’s Figure 2 illustrates a process of isolating an anti-idiotypic anti-
receptor antibody by: (1) using a ligand to generate anti-ligand antibodies;
(2) generating anti-idiotypic antibodies directed against the anti-ligand
antibodies; (3) isolating specific anti-idiotypic antibodies that interact with
the receptor of interest (Taub 7432).
9. Taub teaches “anti-idiotypic antibodies prepared by
immunization with specific anti-ligand antibodies can be selected for their
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ability to interact with the specific receptor and block ligand binding by the
receptor” (Taub 7432).
10. Taub teaches “[s]ome of these anti-idiotypic antibodies react
not only with the anti-ligand antibody but also with the receptor combining
site, thus mimicking the binding of the ligand” (Taub 7432).
11. Taub teaches anti-idiotypic antibodies, including monoclonal
antibodies “have been isolated that are directed against a wide variety of
receptors . . . The most characteristic property of anti-receptor antibodies
that bind to the ligand binding site is their ability to specifically inhibit
ligand binding by the receptor” (Taub 7432).
12. Sutherland teaches a process for generating monoclonal
antibodies to human NKG2D (Sutherland 672).
Principles of Law
The Examiner has the initial burden of establishing a prima facie case
obviousness under 35 U.S.C. § 103. In re Oetiker, 977 F.2d 1443, 1445
(Fed. Cir. 1992). “The combination of familiar elements according to
known methods is likely to be obvious when it does no more than yield
predictable results.” KSR Int'l Co. v. Teleflex Inc., 550 U.S. 398, 416
(2007).
Analysis
We adopt the Examiner’s findings of fact and conclusion of law (see
Ans. 8–27, FF 1–12) and agree that Cosman and Taub render the claims
obvious. We address Appellant’s arguments below.
Appellant contends that “Cosman teaches the use of hypothetical
antibodies that, when treating autoimmunity, bind to NKG2D and inhibit
NKG2D . . . This teaching does not surmount to the use of NKG2D
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antibodies that were known and recognized to bind to NKG2D, be
internalized, and have slight activating properties” (Br. 4). Appellant
contends that Cosman’s “teaching is incompatible with an anti-NKG2D
antibody, since such antibodies were known to have stimulatory activity”
(id. at 4–5). Appellant contends that “Taub does not cure these deficiencies,
since Taub teaches anti-idiotypic antibodies as ‘mimicking the binding of
the ligand’ or that ‘it is not necessary that the antibody mimic the ligand at
the level of biologic properties’” (id. at 5).
We do not find this argument persuasive because as explained above,
we do not find any deficiencies in the teachings of Cosman. Furthermore, as
discussed above, Appellant argues limitations that are not found in the
claims because claim 1 recites administering “a blocking anti-NKG2D
monoclonal antibody” (Br. 15). The claims do not recite an antibody that
binds to NKG2D, is internalized, and has slight activating properties (id., cf.
claim 5 reciting “wherein said antibody interferes with the binding of an
NKG2D ligand to the NKG2D receptor”). As found by the Examiner, the
combination of Cosman and Taub teach that it would have been obvious to
treat Crohn’s Disease by administering a blocking anti-NKG2D monoclonal
antibody that binds to NKG2D and interferes with ligand binding (FF 4, 5, 9,
11).
Appellant argues further that the cited references do not establish a
reasonable expectation of success (Br. 5). First, Appellant contends that
“[t]he knowledge in the art at the time would have at least indicated that
there was no expectation of success, based on the known stimulatory
properties of anti-NKG2D antibodies,” and that Cosman teaches away by
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indicating “that such stimulatory properties may be useful for treating
cancer, but require the opposite action when treating autoimmunity” (id.).
We find Appellant’s argument unpersuasive because Cosman does not
teach away from the invention. See In re Gurley, 27 F.3d 551, 553 (Fed.
Cir. 1994) (“[I]n general, a reference will teach away if it suggests that the
line of development flowing from the reference’s disclosure is unlikely to be
productive of the result sought by the applicant.”) As discussed above,
Cosman teaches treating Crohn’s Disease by administering a blocking anti-
NKG2D monoclonal antibody, i.e., the same result sought by Appellant.
Cosman does not teach away by disclosing an alternative method of treating
cancer by using ULBP peptides or anti-idiotypic antibodies for activating
cells that express NKG2D, as the alternative method does not criticize,
discredit or otherwise discourage treating Crohn’s Disease. See In re Fulton,
391 F.3d 1195, 1201 (Fed. Cir. 2004).
Second, Appellant contends that Cosman teaches that “autoimmune
diseases have very different causes and symptoms, and such cases are
usually unclear” (Br. 6). Given this uncertainty, Appellant contends that
“any use of a NKG2D antibody appears to [] be merely hypothetical” as
“Cosman has not tested for the ability of a NKG2D antibody to treat Crohn’s
Disease” (id. at 5). Further, Appellant contends that “Taub teaches that anti-
idiotype antibodies with varying activities” and “one skilled in the art would
not combine the cited references of Cosman and Taub to arrive at the
claimed method for treating Crohn’s disease” (id. at 4–5).
We do not find Appellant’s argument persuasive because obviousness
does not require absolute predictability of success. See In re O’Farrell, 853
F.2d 894, 903–904 (Fed. Cir. 1988). Rather, “[w]hat does matter is whether
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the prior art gives direction as to what parameters are critical and which of
many possible choices may be successful.” Allergan, Inc. v. Apotex Inc.,
754 F.3d 952, 965 (Fed. Cir. 2014). As discussed above, Cosman teaches
treating Crohn’s Disease with a blocking anti-NKG2D antibody. Taub
teaches isolating anti-idiotypic antibodies directed against a wide variety of
receptors, all of which share the ability to bind to the receptor of interest (FF
11). Sutherland confirms that monoclonal antibodies targeting NKG2D
were known in the art (FF 12). Accordingly, the prior art describes both the
critical parameters for treating Crohn’s disease, i.e., blocking NKG2D, and
the specific therapeutics for doing so, i.e., anti-NKG2D monoclonal
antibodies. While the success in employing anti-NKG2D monoclonal
antibodies to treat Crohn’s Disease may not have been guaranteed, the prior
art teachings provided sufficient guidance as to what parameters would lead
to a reasonable expectation of success. See 754 F.3d at 965.
Conclusion of Law
A preponderance of the evidence of record support the Examiner’s
conclusion that Cosman and Taub render the claims obvious.

C. 35 U.S.C. § 103(a) over Cosman, Taub, the Spies Declaration, and
Bauer, as evidenced by Sutherland
The Examiner finds that Cosman and Taub do not explicitly teach
administering a blocking anti-NKG2D antibody, wherein the antibody
downregulates the expression of NKG2D on cells. (Ans. 21). Claim 37
recites the method of claim 1, “wherein the antibody downregulates the
expression of NKG2D on cells” (Br. 15). To cure the deficiency of Cosman
and Taub, the Examiner finds that the Spies Declaration explains that “it was
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known prior to appellant’s filing date that internalization of human NKG2D
can be induced by the binding of its ligands” (id., citing Spies Decl. ¶ 10)
(emphasis omitted). The Examiner finds that the Spies Declaration explains
that “prior to appellant’s date of invention assays were known and available
in the field that could be used to determine if an anti-NKG2D monoclonal
antibody blocks and/or downregulates the expression of NKG2D on cells”
(id. at 22, citing Spies Decl. ¶ 11, 12). The Examiner finds that one of
ordinary skill in the art would have been motivated to screen for NKG2D-
binding antibodies that downregulate expression of NKGD2D on cells,
“given the knowledge in the prior art described in the Groh Spies declaration
supporting that an antibody to NKG2D would have been expected by the
ordinarily skilled artisan to induce internalization and downregulate the
expression of NKG2D on cells” (id.) (emphasis omitted).
Appellant argues against the rejection of claim 37 by first asserting
that “claim 37 requires an antibody with activating activities” (Br. 8).
Appellant supports this argument with the Spies Decl. which states “that
binding of specific anti-NKG2D antibodies to NKG2D may activate
NKG2D; and therefore, it would be expected that the activation of NKG2D
by the anti-NKG2D antibodies likely also induced internalization of cell
surface NKG2D” (id., quoting Spies Decl. ¶ 10) (emphasis omitted).
Appellant contends that “antibodies that downregulate the expression of
NKG2D on cells are antibodies that stimulate NKG2D and Cosman teaches
that stimulation of NKG2D treats cancer and inhibition of activation of
NKG2D treats autoimmunity” (id. at 9) (emphasis omitted). Appellant
contends that one would not screen for blocking antibodies that
downregulate the expression of NKG2D because “the prior art teaches the
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administration of blocking antibodies that inhibit activation of the receptor,
and such antibodies are antibodies with (at least) some stimulating activity”
(id.)
We do not find Appellant’s argument persuasive because claim 37
does not recite “an antibody with activating activities.” Rather, claim 37
recites a blocking antibody that “downregulates the expression of NKG2D
on cells.” The Examiner has established that one of ordinary skill in the art
would have been motivated to administer a blocking anti-NKG2D antibody
that downregulates the expression of NKG2D on cells. Appellant has not
shown that the blocking antibody taught by Cosman, Taub, the Spies
Declaration, and Bauer would not downregulate the expression of NKG2D
on cells. See In re Best, 562 F.2d at 1254–1255. Rather, the Spies
Declaration indicates that antibody binding to NKG2D would have been
expected to downregulate the expression of NKG2D on cells. “It is a general
rule that merely discovering and claiming a new benefit of an old process
cannot render the process again patentable.” In re Woodruff, 919 F.2d 1575,
1578 (Fed. Cir. 1990).
Second, Appellant contends that the references do not establish a
reasonable expectation of success for the reasons provided as to claim 1 (see
Br. 10–11). For the reasons provided above, we do not find Appellant’s
arguments persuasive.
Conclusion of Law
A preponderance of the evidence of record support the Examiner’s
conclusion that Cosman, Taub, the Spies Declaration, and Bauer render the
claims obvious.

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D–G. 35 U.S.C. § 103(a) over Cosman, Taub, the Spies Declaration, Bauer,
Strom, Deventer, the Humira press release, and Melief
Appellant does not substantively argue these obviousness rejections,
instead relying on upon their arguments to overcome Cosman and Taub (see
Br. 12). The Examiner provides sound fact-based reasoning for combining
the references (see Ans. 28–29). Having affirmed the obviousness rejection
of claim 1 over Cosman and Taub for the reasons given above, we also find
that the further combinations render the claims obvious for the reasons given
by the Examiner.

H. 35 U.S.C. § 112, first paragraph, enablement
The Examiner finds claim 8 unpatentable under 35 U.S.C. § 112, first
paragraph, because the Specification does not reasonably provide
enablement for a method of treating Crohn’s disease by administering a
blocking anti-NKG2D monoclonal antibody and “any inhibitor of TNF-
alpha or IL-15” (Ans. 30; see also Non-Final Act. of Sept. 14, 2018, 20–21).
The Examiner finds that “the instant specification does not provide sufficient
direction or guidance for the skilled artisan to make the breadth of
compositions that neutralize TNFα or IL-15, including small molecules, in
view the low level of knowledge in the art” (id. at 31). The Examiner
supports this finding with evidence in the art teaching the difficulty in
identifying small molecule cytokine inhibitors (see id.). The Examiner finds
that “the instant claims encompass an invention of tremendous breadth, and
undue experimentation would be required of the skilled artisan to begin
discovering how to practice the claimed invention” (id.).
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Appellant contends that “[f]ollowing from the acknowledgement of
the enablement of the method of claim 1, the Examiner has not provided any
evidence or arguments as to why further administration of an additional
therapeutic agent would reverse the enablement of the current claims” (Br.
13). However, as discussed above, the Examiner has provided both
arguments and evidence as to why claim 8 lacks enablement. Appellant fails
to raise a substantive argument in response to the Examiner’s rejection. “If
an appellant fails to present arguments on a particular issue – or, more
broadly, on a particular rejection – the Board will not, as a general matter,
unilaterally review those uncontested aspects of the rejection.” Ex parte
Frye, 94 USPQ2d 1072, 1075 (BPAI 2010) (precedential). Accordingly, we
summarily affirm the Examiner’s rejection of claim 8.

DECISION SUMMARY
In summary:
Claims
Rejected
35 U.S.C. § Reference(s)/Basis Affirmed Reversed
1, 3, 9, 10 102 Cosman, Allez 1, 3, 9, 10
1, 3, 9, 10 103 Cosman, Taub,
Sutherland
1, 3, 9, 10
1, 3, 4, 5,
9, 10, 37
103 Cosman, Taub, Spies
Decl., Bauer,
Sutherland
1, 3, 4, 5, 9,
10, 37

1, 8 103 Cosman, Deventer,
Strom
1, 8
1, 35 103 Cosman, Humira press
release
1, 35
1, 36 103 Cosman, Taub, Melief,
Sutherland, Jamieson
1, 36
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Claims
Rejected
35 U.S.C. § Reference(s)/Basis Affirmed Reversed
1, 36, 38 103 Cosman, Taub, Spies
Decl., Melief, Humira,
Sutherland, Jamieson
1, 36, 38
8 112, first
paragraph
Lack of enablement 8
12, 13 112, second
paragraph
Indefinite 12, 13
Overall
Outcome
1, 3–5, 8–10,
12–13, 35–38

No time period for taking any subsequent action in connection with
this appeal may be extended under 37 C.F.R. § 1.136(a).

AFFIRMED