Ex Parte Grunewald et al

Patent Trial and Appeal Board

Apr 28, 2016

12735575 (P.T.A.B. Apr. 28, 2016)

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.
12/735,575 11/05/2010 Jan Grunewald 54-002751US 7154
22798 7590 04/29/2016
QUINE INTELLECTUAL PROPERTY LAW GROUP, P.C.
P O BOX 458
ALAMEDA, CA 94501
EXAMINER
ROGERS, JAMES L
ART UNIT PAPER NUMBER
1644
MAIL DATE DELIVERY MODE
04/29/2016 PAPER
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.
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
__________

BEFORE THE PATENT TRIAL AND APPEAL BOARD
__________

Ex parte JAN GRUNEWALD, MENG-LIN TSAO, ROSHAN PERERA,
RICHARD A. LERNER, VAUGHN V. SMIDER, and
PETER G. SCHULTZ1
__________

Appeal 2013-009909
Application 12/735,575
Technology Center 1600
__________

Before ERIC B. GRIMES, MELANIE L. McCOLLUM, and
JACQUELINE T. HARLOW, Administrative Patent Judges.

GRIMES, Administrative Patent Judge.

DECISION ON APPEAL
This is an appeal under 35 U.S.C. § 134(a) involving claims to a
method of preventing or treating a disease, which have been rejected for
nonenablement and obviousness-type double patenting. We have
jurisdiction under 35 U.S.C. § 6(b).
We affirm.

1 Appellants identify the real party in interest as The Scripps Research
Institute. (Appeal Br. 1.)
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STATEMENT OF THE CASE
The Specification discloses “compositions and methods for producing
an immunological response in a subject against a self-antigen, e.g., TNFα
. . . by administering an immunogen that corresponds to a target moiety . . .
into which one or more unnatural amino acids have been incorporated.”
(Spec. ¶ 3.) The Specification states that the unnatural amino acid can be
p-nitrophenylalanine (pNO2). (Id. at ¶ 12.)
The Specification states that “[i]n some embodiments the target self-
moiety is TNFα and the unnatural immunogen is an unnatural TNFα. For
example, in embodiments in which the subject is a mouse, the target moiety
can be mTNFα. . . . Similarly, in embodiments in which the subject is a
human, the target self-moiety can be an hTNFα.” (Id. at ¶ 17.)
The Specification also states that “the target moiety against which an
immunological response is produced or enhanced can be a non-self moiety,
e.g., a moiety derived from a bacterium, a virus, a fungus, a Mycoplasma, a
protozoan, a helminth, or a prion.” (Id. at ¶ 13.)
Claims 34–37, 39, 41–47, 54–61, 65–67, 116–118, and 120 are on
appeal. Claims 34, 35, and 43 are illustrative and read as follows:
34. A method of prophylactically or therapeutically treating a
disease state in a subject, the method comprising:
administering an unnatural immunogen to the subject,
which immunogen comprises one or more unnatural amino
acids and which unnatural immunogen stimulates production of
antibodies within the subject that are cross-reactive against a
target moiety, wherein the target moiety is TNFα;
wherein the unnatural immunogen is an unnatural
mTNFα, and the one or more unnatural amino acids is or are
selected from the group consisting of: a pNO2Phe11-mTNFα, a
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pNO2Phe19-mTNFα, a pNO2Phe21-mTNFα, a pNO2Phe42-
mTNFα, a pNO2Phe49-mTNFα, a pNO2Phe86-mTNFα, a
pNO2Phe104-mTNFα, a pNO2Phe113-mTNFα; or
wherein the unnatural immunogen is an unnatural
hTNFα, and the one or more unnatural amino acids is or are
selected from the group consisting of: a pNO2Phe11-hTNFα, a
pNO2Phe19-hTNFα, a pNO2Phe21-hTNFα, a pNO2Phe42-hTNFα,
a pNO2Phe49-hTNFα, a pNO2Phe87-hTNFα, a pNO2Phe105-
hTNFα, and a pNO2Phe114-hTNFα;
and
wherein the pNO2Phe unnatural amino acid residues are
numbered relative to the mature mTNFα and hTNFα
polypeptides.

35. A method of prophylactically or therapeutically treating a
disease state in a subject, the method comprising:
producing an antibody against a target moiety, wherein
the target moiety is TNFa, such producing comprising making
an antibody against an unnatural immunogen which unnatural
immunogen comprises one or more unnatural amino acids, and
which antibody is cross-reactive against TNFa; and,
administering the antibody to the subject;
wherein the unnatural immunogen is an unnatural
mTNFα, and the one or more unnatural amino acids is or are
selected from the group consisting of: a pNO2Phe11-mTNFα, a
pNO2Phe19-mTNFα, a pNO2Phe21-mTNFα, a pNO2Phe42-
mTNFα, a pNO2Phe49-mTNFα, a pNO2Phe86-mTNFα, a
pNO2Phe104-mTNFα, a pNO2Phe113-mTNFα; or
wherein the unnatural immunogen is an unnatural
hTNFα, and the one or more unnatural amino acids is or are
selected from the group consisting of: a pNO2Phe11-hTNFα, a
pNO2Phe19-hTNFα, a pNO2Phe21-hTNFα, a pNO2Phe42-hTNFα,
a pNO2Phe49-hTNFα, a pNO2Phe87-hTNFα, a pNO2Phe105-
hTNFα, and a pNO2Phe114-hTNFα;
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and
wherein the pNO2Phe unnatural amino acid residues are
numbered relative to the mature mTNFα and hTNFα
polypeptides.

43. The method of claim 34 or 35, wherein the disease state is
an autoimmune disorder, a cancer, a bacterial infection, a viral
infection, a fungal infection, a Mycoplasma infection, a prion
infection, a protozoan infection, or a helminth infection.

I
The Examiner has rejected all of the claims on appeal under 35 U.S.C.
§ 112, first paragraph, as nonenabled. (Final Rej.2 4.) The Examiner finds
that the Specification “exemplifies a model for one possible disease
currently within the scope of the claims, endotoxemia. Specifically, the
specification discloses that vaccination of mice with the pNO2Phe86 TNFα
protected mice against an LPS challenge in a severe endotoxemia mouse
model.” (Id. at 5.)
However, the Examiner finds that “it is not clear that reliance on the
limited in vivo data of a mouse model for endotoxemia reflects the relative
mammal efficacy of the claim therapeutic strategy for treating any type of
disease or an autoimmune disorder (elected species) as is currently within
the scope of claims.” (Id.) The Examiner cites Buras3 as evidence that
clinical studies of sepsis have proven difficult to perform and that animal

2 Office Action mailed July 24, 2012.
3 Buras et al., Animal Models of Sepsis: Setting the Stage, 4 Nature
Reviews/Drug Discovery 854–65 (2005).
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models have not been shown to be predictive of results that were achieved in
human clinical trials. (Id.)
The Examiner also finds that “the unpredictability in the art with
respect to amino acid substitutions and induction of an immunological
response against a natural self-target moiety is high.” (Id. at 6, citing
Thomas.4) With regard to autoimmune diseases, the Examiner cites
Mackay5 as evidence that “overexpression or under expression of particular
cytokines/proteins depend upon the particular type of autoimmune disease
and the difficulty in predicting cytokine/protein functions when they are
overexpressed or under expressed.” (Id. at 8.)
The Examiner concludes that “[i]n view on the quantity of
experimentation necessary the limited working examples, the nature of the
invention, the state of the prior art, the unpredictability of the art and the
breadth of the claims, it would take undue trials and errors to practice the
claimed invention.” (Id.)
Appellants contend that “the vast bulk of the teaching, examples, and
discussion in the cited articles strongly support a finding of enablement for
the present claims.” (Br. 4.) Appellants argue that Buras discloses that anti-
TNFα treatment successfully treats sepsis (id. at 4–5) and Mackay states that
“anti-TNF-α treatments have been found effective when administered to

4 Thomas et al., Nature of T Lymphocyte Recognition of Macrophage-
Associated Antigens. V. Contribution of Individual Peptide Residues of
Human Fibrinopeptide B to T Lymphocyte Responses., 152 J. Exp. Med.
620–32 (1980).
5 Mackay et al. (eds.), Autoimmune Diseases, 345 New England Journal of
Medicine 340–50 (2001).
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humans for treatment of rheumatoid arthritis, Crohn’s disease, systemic
lupus erythematosus, refractory psoriatic arthritis, ankylosing spondylitis,
and refractory psoriasis.” (Id. at 7.) Appellants argue that the “Thomas
reference is all but immaterial,” because it addresses a different protein and
its effect on T-cell response in guinea pigs. (Id.) Appellants also argue that
the factors set out in In re Wands, 858 F.2d 731, 737 (Fed. Cir. 1988),
support a conclusion of enablement. (Br. 9–12.)
We conclude that a preponderance of the evidence of record supports
the Examiner’s conclusion that undue experimentation would be required to
practice the full scope of claims 34 and 35. As the Examiner has pointed
out, although the Specification provides a working example of treating
endotoxemia in a mouse model, that does not “reflect[ ] the relative mammal
efficacy of the claim[ed] therapeutic strategy for treating any type of disease
or an autoimmune disorder (elected species) as is currently within the scope
of claims.” (Final Rej. 5.)
The Examiner points specifically to dependent claim 43 (Ans. 8),
which encompasses treating “an autoimmune disorder, a cancer, a bacterial
infection, a viral infection, a fungal infection, a Mycoplasma infection, a
prion infection, a protozoan infection, or a helminth infection.” Appellants
have pointed to evidence showing that some autoimmune disorders can be
treated with anti-TNFα agents, but have not pointed to any evidence
showing that anti-TNFα agents can effectively treat cancer, bacterial
infections, viral infections, fungal infections, Mycoplasma infections, prion
infections, protozoan infections, or helminth infections.
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We note that claim 43 is an original claim and depends from either
claim 34 or claim 35. However, as originally written, claims 34 and 35 were
not limited to TNFα-based immunogens, but recited an unnatural
immunogen generically. Both of the independent claims on appeal are now
limited to an unnatural immunogen that is based on TNFα, but they
encompass treatment of cancer or infections for which there is no evidence
of record showing that anti-TNFα treatment is effective. We therefore agree
with the Examiner that practicing the full scope of the claimed methods
would require undue experimentation.
Claims 36, 37, 39, 41–47, 54–61, 65–67, 116–118, and 120 have not
been argued separately and therefore fall with claims 34 and 35. 37 C.F.R.
§ 41.37(c)(1)(iv).
II
The Examiner has rejected all of the claims on appeal for
obviousness-type double patenting based on claims 1–3, 8, 10, 11, 20–25,
29, 30, 71, 121–123, 125, and 126 of U.S. Patent 8,318,172. (Ans. 3–4.)
Appellants did not provide arguments disputing this rejection in the Appeal
Brief. Therefore, we affirm it. See Hyatt v. Dudas, 551 F.3d 1307, 1314
(Fed. Cir. 2008) (“When the appellant fails to contest a ground of rejection
to the Board, . . . the Board may treat any argument with respect to that
ground of rejection as waived. In the event of such a waiver, the PTO may
affirm the rejection of the group of claims that the examiner rejected on that
ground without considering the merits of those rejections.”).
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SUMMARY
We affirm both of the rejections on appeal.
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).

AFFIRMED