Ex Parte Schaebitz et al

Patent Trial and Appeal Board

Dec 11, 2012

11931326 (P.T.A.B. Dec. 11, 2012)

UNITED STATES PATENT AND TRADEMARK OFFICE
__________

BEFORE THE PATENT TRIAL AND APPEAL BOARD
__________

Ex parte WOLF-RUEDIGER SCHAEBITZ,
ARMIN SCHNEIDER, CAROLA KRUEGER, CLEMENS SOMMER,
STEFAN SCHWAB, RAINER KOLLMAR, MARTIN MAURER,
DANIELA WEBER, and NIKOLAUS GASSLER
__________

Appeal 2011-001820
Application 11/931,326
Technology Center 1600
__________

Before TONI R. SCHEINER, FRANCISCO C. PRATS, and
JACQUELINE WRIGHT BONILLA, Administrative Patent Judges.

PRATS, Administrative Patent Judge.

DECISION ON APPEAL
This appeal under 35 U.S.C. § 134 involves claims to treating
amyotrophic lateral sclerosis (ALS). The Examiner entered rejections for
anticipation and obviousness.
We have jurisdiction under 35 U.S.C. § 6(b). We affirm three of the
Examiner‟s four anticipation rejections. We also affirm the Examiner‟s
obviousness rejection.

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STATEMENT OF THE CASE
Claims 1, 20-22, and 59-75 stand rejected and appealed (App. Br. 2).
Claims 1 and 65, the independent claims, illustrate the appealed subject
matter and read as follows:
Claim 1. A method of treating amyotrophic lateral sclerosis
in a mammal, consisting of administering to the mammal in need
thereof, a hematopoietic factor selected from the group consisting of
mammalian granulocyte colony stimulating factor (G-CSF), human
G-CSF, a protein having at least 90% homology to SEQ ID NO:37
and G-CSF activity, a protein having at least 90% homology to SEQ
ID NO:38 and G-CSF activity, a protein having at least 90%
homology to SEQ ID NO:39 and GCSF activity, PEG-modified
G-CSF, or a combination thereof in an amount sufficient to treat the
amyotrophic lateral sclerosis.

Claim 65. A method of treating amyotrophic lateral sclerosis
caused by a SOD1 mutation in a mammal, comprising administering
to the mammal in need thereof, a hematopoietic factor selected from
the group consisting of mammalian granulocyte colony stimulating
factor (G-CSF), human G-CSF, a protein having at least 90%
homology to SEQ ID NO:37 and G-CSF activity, a protein having at
least 90% homology to SEQ ID NO:38 and G-CSF activity, a protein
having at least 90% homology to SEQ ID NO:39 and GCSF activity,
PEG-modified G-CSF, or a combination thereof in an amount
sufficient to treat the amyotrophic lateral sclerosis.

The following rejections are before us for review:
(1) Claims 1, 20-22, 60-68, and 70-75, under 35 U.S.C. § 102(b) as
anticipated Faustman „346
1
(Ans. 4-6);
(2) Claims 1, 20-22, 60-68, and 70-75, under 35 U.S.C. §§ 102(a) and
102(e) as anticipated by Faustman „689
2
(Ans. 6-8);

1
WO 99/43346 A1 (published September 2, 1999).
2
U.S. Patent App. Pub. No. 2002/0106689 A1 (published August 8, 2002).
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(3) Claims 1, 20-22, and 59-75, under 35 U.S.C. §§ 102(a) and 102(e)
as anticipated by Chajut
3
(Ans. 8-9);
(4) Claims 65-75, under 35 U.S.C. § 102(b) as anticipated by North
4

(Ans. 9-10); and
(5) Claims 59 and 69, under 35 U.S.C. § 103(a) as obvious over
Faustman „346 or Faustman „689 (Ans. 10-14).
ANTICIPATION – THE FAUSTMAN PUBLICATIONS
Appellants contend that “Faustman US „689 is the national stage filing
of Faustman WO „346” (App. Br. 6). While that fact is not apparent from
either publication, the relevant disclosures of Faustman „346 and Faustman
„689 do in fact appear to be substantially the same. We therefore consider
the Examiner‟s anticipation rejections over both Faustman publications
together.
As stated in In re Oetiker, 977 F.2d 1443, 1445 (Fed. Cir. 1992):
[T]he examiner bears the initial burden . . . of presenting a
prima facie case of unpatentability. . . .
After evidence or argument is submitted by the applicant
in response, patentability is determined on the totality of the
record, by a preponderance of evidence with due consideration
to persuasiveness of argument.

Appellants‟ arguments do not persuade us that a preponderance of the
evidence fails to support the Examiner‟s prima facie case that the Faustman
publications anticipate claim 1.

3
U.S. Patent App. Pub. No. 2002/0198150 A1 (published December 26,
2002).
4
Will A. North et al., Reversible Granulocytopenia in Association with
Riluzole Therapy, 34 Annals of Pharmacotherapy 322-32 (2000).
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Claim 1 recites a method of treating amyotrophic lateral sclerosis
(ALS) in a mammal. The method consists of administering a hematopoietic
factor, which may be mammalian granulocyte colony stimulating factor (G-
CSF), to the mammal in need of such treatment. The G-CSF must be
administered in an amount sufficient to treat the ALS.
Faustman „346 discloses “a method of treating an autoimmune disease
in a mammal, comprising administering to a mammal suspected of suffering
from an autoimmune disease an agent which restores NFκB activity in an
amount and for a time sufficient to result in normal NFκB activity in the
mammal” (Faustman „346 at p. 16; see also Faustman „689 at [0104]).
Faustman then discloses that, “[p]referably, the agent is selected from
the group that consists of a protein and a nucleic acid that encodes that
protein” and, further, that “[i]t is preferred that the protein is selected from
the group that includes . . . granulocyte colony-stimulating factor . . .”
(Faustman „346 at pp. 16-17; see also Faustman „689 at [0106]-[0107]).
Faustman then discloses that, “[i]n another preferred embodiment, the
autoimmune disease is selected from the group that includes those diseases
listed above” (Faustman „346 at p. 17), among which is ALS (see id. at p. 7;
see also Faustman „689 at [0112] and [0031]). Thus, as the Examiner
pointed out, Faustman describes treating the claimed disorder with the
claimed therapeutic agent.
We acknowledge, as Appellants argue, that in an anticipation rejection
“it is not enough that the prior art reference . . . includes multiple, distinct
teachings that [an ordinary] artisan might somehow combine to achieve the
claimed invention.” NetMoneyIN, Inc. v. VeriSign, Inc., 545 F.3d 1359,
1371 (Fed. Cir. 2008). Rather, the reference “must clearly and
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unequivocally disclose the claimed [invention] or direct those skilled in the
art to the [invention] without any need for picking, choosing, and combining
various disclosures not directly related to each other by the teachings of the
cited reference.” Id. (quoting In re Arkley, 455 F.2d 586, 587 (CCPA 1972).
We also acknowledge that Faustman lists ALS alongside about 56
other diseases that can be treated (see Faustman „346 at page 7), and that
G-CSF is listed alongside about 23 other agents that can be used to treat
those diseases (see id. at 17). However, because the specifically listed
diseases and specifically listed treating agents do not number in the
thousands, or multiple thousands, or more, we are not persuaded that
Faustman‟s description of which diseases to treat, and which agents to use,
amounts to a meaningless description of treating any of a “plethora” of
disorders, as Appellants argue (App. Br. 6).
To the contrary, because the Faustman publications lay out the
NFκB-related treatment methods in a sequential manner that evidences a
direct relationship between a list of specific “preferred” treatment agents
(see Faustman „346 at p. 16; Faustman „689 at [0107]), and a list of specific
“preferred” diseases to be treated with those agents (id. Faustman „346 at 17;
Faustman „689 at [0112]), we agree with the Examiner that improper picking
and choosing of unrelated disclosures is not required to “at once envisage”
claim 1‟s treatment of ALS with G-CSF. See In re Petering, 301 F.2d 676,
681 (CCPA 1962) (chemical compounds held anticipated where reference
disclosing generic formula also included preferences for claimed
substituents).
Further, we are not persuaded that Appellants have advanced evidence
adequately demonstrating that the Faustman publications did not enable an
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ordinary artisan to treat ALS with G-CSF. We note the disclosures in Silani
5

and Jackson
6
that the hypothesized link between autoimmunity and ALS is
waning in popularity, as well as the disclosures in Jackson and Jerusalem
7

that attempts at treating ALS with immunologically-based had been
unsuccessful (see Silani at p. 25 (abstract); Jackson at p. 34; Jerusalem at p.
S218).
As Appellants point out, however, “in the context of a claimed
method for treating a disease, a prior art reference need not disclose „proof
of efficacy‟ to anticipate the claim.” In re Gleave, 560 F.3d 1331, 1335
(Fed. Cir. 2009) (citing Impax Labs., Inc. v. Aventis Pharms. Inc., 545 F.3d
1312, 1314 (Fed. Cir. 2008); Rasmusson v. SmithKline Beecham Corp., 413
F.3d 1318, 1326 (Fed. Cir. 2005)).
Thus, the fact that autoimmunity might not be the most popular
causative hypothesis for ALS among those skilled in the art does not provide
sufficient clear or specific evidence to persuade us that an ordinary
practitioner, armed with Faustman‟s disclosure of treating ALS with G-CSF,
would have been able to practice Faustman‟s method only through undue
experimentation.
Therefore, as Appellants‟ arguments do not persuade us that the
Examiner erred in maintaining the anticipation rejection of claim 1 over the
Faustman publications, we affirm the Examiner‟s rejections of that claim

5
Vincenzo Silani et al., Patogeneza SLA: implikacje dla leczenia, NEUR.
NEUROCHIR. POL. Supp.I 25-39 (2001).
6
Carlayne E. Jackson and Wilson W. Bryan, Amyotrophic Lateral Sclerosis,
18 SEMINARS IN NEUROLOGY 27-39 (1998).
7
F. Jerusalem et al., ALS, 47 NEUROLOGY Suppl. 4 S218-S220 (1996).
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over those references. As they were not argued separately, claims 20-22 and
60-64 fall with claim 1. See 37 C.F.R. § 41.37(c)(1)(vii).
Appellants‟ arguments also fail to persuade us that the Examiner erred
in maintaining the anticipation rejections over the Faustman publications as
to claim 65. Claim 65, like claim 1, encompasses treating mammals having
ALS with G-CSF, but limits the treated subjects to those having ALS
“caused by a SOD1 mutation” (App. Br. 17).
We note Silani‟s disclosure that the SOD1 mutation in the superoxide
dismutase gene is observed in a subset of ALS sufferers:
Besides the free radical hypothesis raised by the identification
of Superoxide Dismutase 1 mutations in a subset of familiar
Amyotrophic Lateral Sclerosis (ALS) patients, three
etiopathogenic hypotheses for sporadic ALS, namely
autoimmune, neurofilament, and glutamate toxicity, have
attracted interest in the last few years. The role of
autoimmunity in ALS has been seriously questioned.

(Silani at p. 25.) We also note Appellants‟ assertion that, in their hands,
G-CSF exhibited a trend toward increasing life expectancy in a transgenic
mouse model of ALS that includes an SOD1 mutation (see, e.g. Spec. 163
(Example 33)).
Appellants have not, however, advanced clear or specific evidence
suggesting that, despite the fact that they suffer from the same disorder, the
subset of ALS sufferers exhibiting the SOD1 mutation would have been
viewed sufficiently differently from ALS sufferers generally, such that an
ordinary artisan viewing Faustman‟s disclosure of treating ALS with G-CSF
would have failed to envisage treating the SOD1-carrying patients with that
agent. Thus, as Appellants‟ arguments do not persuade us that the Examiner
erred in maintaining the anticipation rejections of claim 65 over the
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Faustman publications we affirm those rejections as well. Claims 66-68 and
70-75 fall with claim 65. See 37 C.F.R. § 41.37(c)(1)(vii).
OBVIOUSNESS – THE FAUSTMAN PUBLICATIONS
Claims 59 and 69 depend, respectively, from claims 1 and 65, and
both require the hematopoietic factor, which may be G-CSF, to be
administered daily (see App. Br. 16 (claim 59); see also id. at 18 (claim 69)).
While the Examiner conceded that the Faustman publications did not
describe daily administration of G-CSF, the Examiner reasoned that an
ordinary artisan practicing Faustman‟s ALS treatment would have
considered it obvious to “modify the teachings of Faustman by formulating a
daily dosage regimen, because both Faustman disclosures clearly provide
guidance to one of ordinary skill in the art as to how to formulate treatment
regimens for proteins” (Ans. 13).
In traversing this rejection, Appellants rely solely on their previous
arguments directed to the anticipation rejection (see App. Br. 11 (“[A]s
discussed above, Faustman does not actually disclose the treatment of ALS
in the manner that is claimed and as such Faustman cannot render Claim 59
obvious.”)).
Thus, as Appellants point to no specific deficiency as to the
Examiner‟s prima facie case of obviousness, and as we are not persuaded,
for the reasons discussed above, that the Examiner erred in maintaining the
anticipation rejection, we affirm the Examiner‟s obviousness rejections over
the Faustman publications.

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ANTICIPATION – CHAJUT
The Examiner rejected claims 1, 20-22, and 59-75, all of the pending
claims, as anticipated by Chajut under 35 U.S.C. §§ 102(a) and 102(e) (see
Ans. 8-9).
Appellants do not argue any of the claims subject to this ground of
rejection separately (see App. Br. 11-13). We select claim 1 as
representative of the rejected claims. See 37 C.F.R. § 41.37(c)(1)(vii).
Appellants‟ arguments do not persuade us that a preponderance of the
evidence fails to support the Examiner‟s prima facie case that Chajut
anticipates claim 1.
Chajut discloses the use of “growth factors that stimulate migration
and differentiation of stem cells, particularly colony stimulating factors
(CSFs), in order to promote and enhance recovery from tissue trauma and
ischemic events, including ischemia of the central nervous system, as well as
for use in preventing or diminishing chronic degenerative changes” (Chajut
[0024]).
Chajut then states:
The compositions of the present invention may also be
effective in treating certain chronic degenerative diseases that
are characterized by gradual selective neuronal loss. In this
connection, the compositions of the present invention are
contemplated as therapeutically effective in the treatment of
Parkinson‟s disease, Alzheimer‟s disease, epilepsy, depression,
ALS (Amyotrophic lateral sclerosis), Huntington‟s disease and
any other disease-induced dementia (such as HIV-induced
dementia, for example).
These effects will be achieved by administering an agent
that stimulates the mobilization of bone marrow-derived stem
cells into the bloodstream. Representative agents useful in the
methods of the invention include, for example, granulocyte-
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colony stimulating factor (G-CSF), granulocyte-macrophage-
colony stimulating factor (GM-CSF), stem cell factor (SCF),
interleukin-3 (IL-3) and interleukin-6 (IL-6). These factors have
all been shown to be capable of mobilizing bone marrow-
derived stem cells . . . .

(Chajut [0027]-[0028] (emphases added, citations omitted).)
We acknowledge that, in addition to ALS, Chajut lists additional
disorders that may be treated according to its methods. We also
acknowledge that, in addition to G-CSF, Chajut lists a number of other
therapeutic agents that may be used to treat those disorders. However, given
the sequential and related manner in which Chajut presents the treated
disorders and the treating agents, as well as the limited number of choices of
both, Appellants‟ arguments do not persuade us that Chajut fails to
adequately describe, in the manner required under § 102, claim 1‟s process
of treating ALS with G-CSF.
Appellants argue that Chajut does not demonstrate, by presentation of
a working example, infiltration of stem cells activated by G-CSF into the
central nervous system (see App. Br. 11-12). Appellants argue that the
disclosures of Chen
8
and Smith
9
similarly cast doubt on whether an ordinary
artisan would have reasonably expected that the mechanism of action
proposed by Chajut would provide an effective treatment of ALS (see id. at
13).

8
Jieli Chen et al., Therapeutic Benefit of Intravenous Administration of Bone
Marrow Stromal Cells After Cerebral Ischemia in Rats, 32 STROKE 1005-
1011 (2001).
9
Richard A. Smith et al., Pharmacokinetics and tolerability of ventricularly
administered superoxide dismutase in monkeys and preliminary clinical
observations in familial ALS, 129 J. NEUR. SCI. (Suppl.) 13-18 (1995).
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We are not persuaded. We note, in an experiment which assessed the
therapeutic effect of intravenously administered stem cells, that Chen
posited that “[d]isruption of the blood-brain barrier may facilitate selective
entry of [stem cells] into ischemic brain compared with nonischemic
contralateral cerebral tissue” (Chen at p. 1010). We also note that, because
of the presence of the blood-brain barrier, Smith evaluated direct central
nervous system administration of the superoxide dismutase protein as a
potential treatment for ALS (see Smith at p. 14).
Appellants do not, however, point to any clear or specific teaching in
Chen or Smith that directly discusses the methods described in Chajut.
Moreover, as noted above, “in the context of a claimed method for treating a
disease, a prior art reference need not disclose proof of efficacy to anticipate
the claim.” In re Gleave, 560 F.3d at 1335 (internal quotations removed).
Consistently, in Rasmusson v. SmithKline Beecham, for example, the
Federal Circuit reversed the BPAI‟s conclusion that a reference describing a
cancer treatment was not enabled for anticipation purposes, despite the fact
that the Board had based its non-enablement conclusion upon findings
supporting the premise that an ordinary artisan would not have believed that
the method described in the reference would be effective, as well as the fact
that the reference itself lacked proof of efficacy. See Rasmusson, 413 F.3d
at 1326.
We are therefore not persuaded that Appellants have advanced
evidence adequately demonstrating that the method of treating ALS with
G-CSF described in Chajut is not enabled for anticipation purposes.
Accordingly, as Appellants‟ arguments do not persuade us that the Examiner
erred in maintaining the anticipation rejection of claim 1 over Chajut, we
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affirm that rejection. Claims 20-22 and 59-75 fall with claim 1. See 37
C.F.R. § 41.37(c)(1)(vii).
ANTICIPATION – NORTH
The Examiner also rejected claims 65-75 under 35 U.S.C. § 102(b) as
anticipated by North (Ans. 9-10).
As Appellants point out, and as pointed out above, claim 65
encompasses treating mammals having ALS with G-CSF, but limits the
treated subjects to those having ALS “caused by a SOD1 mutation” (App.
Br. 17).
In this instance, we agree with Appellants that a preponderance of the
evidence does not support the Examiner‟s prima facie case of anticipation.
In particular, we are not persuaded that the Examiner has advanced
sufficient evidence to support a finding that the patient treated in North
inherently suffered from ALS caused by an SOD1 mutation, as claim 65
requires.
It is well settled in the law of anticipation that the “very essence of
inherency is that one of ordinary skill in the art would recognize that a
reference unavoidably teaches the property in question.” Agilent
Technologies, Inc. v. Affymetrix, Inc., 567 F.3d 1366, 1383 (Fed. Cir. 2009)
(emphasis added); see also In re Oelrich, 666 F.2d 578, 581 (CCPA 1981)
(“Inherency, however, may not be established by probabilities or
possibilities. The mere fact that a certain thing may result from a given set
of circumstances is not sufficient.”).
Thus, if “the disclosure is sufficient to show that the natural result
flowing from the operation as taught would result in the performance of the
questioned function, it seems to be well settled that the disclosure should be
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regarded as sufficient.” Oelrich, 666 F. 2d at 581 (quoting Hansgirg v.
Kemmer, 102 F.2d 212, 214 (CCPA 1939)).
Here, North describes treating a single ALS patient with filgramstim
(North 322, abstract), which is undisputed on this record to be a
“pharmaceutical version of G-CSF” (Ans. 3). North explains that the ALS
patient experienced granulocytopenia as an apparent side effect of the
riluzole that was being administered to treat the ALS (North 322, abstract).
North reported that “[b]lood counts returned to normal with discontinuation
of riluzole and administration of filgramstim” (id.).
However, as pointed out in Silani, only a subset of ALS sufferers has
the SOD1 mutation (see Silani 25 (abstract)). Thus, because the Examiner
has pointed to no evidence supporting a finding that North‟s patient
necessarily had the SOD1 mutation, the evidence of record at best shows
that there was a possibility that North‟s patient had the SOD1 mutation.
As noted above, however, inherency may not be established by
probabilities or possibilities. In re Oelrich, 666 F.2d at 581.
The Examiner argues that “[w]hether a person develops ALS because
of a SOD1 mutation or glutamate toxicity is a distinction without a
difference. The person of ordinary skill in the art, as evidenced by Smith et
al. above, would not differentiate in his or her treatment between a patient
with FALS [familial ALS] or ALS (Ans. 41).
We acknowledge the statement in Smith (a different reference) cited
by the Examiner: “[T]he similar clinical course and histopathology of
sporadic ALS and FALS, whether or not there is an SOD gene mutation,
suggest that common molecular mechanisms, and hence a common approach
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to treatment, may apply to all forms of this devastating disease” (Smith 13
(citation omitted).
We also acknowledge that this statement supports a finding that an
ordinary artisan would have understood that a generic description of treating
ALS would not differentiate between patients exhibiting different
hypothetical causative factors, such as SOD1 mutation.
Unlike the Faustman and Chajut rejections discussed above, however,
the Examiner points to no disclosure in North that describes treating ALS
sufferers, as a generic class of patients, with G-CSF. Rather, as also noted
above, North describes treating a single patient, and the Examiner points to
no evidence suggesting that patient was necessarily a member of the subset
of ALS sufferers having the SOD1 mutation.
Accordingly, as we are not persuaded that the Examiner has advanced
adequate evidence to support a finding that the sole patient treated in North
necessarily had ALS caused by an SOD1 mutation as required by claim 65,
we reverse the Examiner‟s rejection of that claim, and its dependents over
North.
SUMMARY
We affirm the Examiner‟s rejection of claims 1, 20-22, 60-68, and 70-
75, under 35 U.S.C. § 102(b) as anticipated Faustman „346.
We also affirm the Examiner‟s rejection of claims 1, 20-22, 60-68,
and 70-75, under 35 U.S.C. §§ 102(a) and 102(e) as anticipated by Faustman
„689.
We also affirm the Examiner‟s rejection of claims 1, 20-22, and 59-
75, under 35 U.S.C. §§ 102(a) and 102(e) as anticipated by Chajut.
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We also affirm the Examiner‟s rejection of claims 59 and 69, under 35
U.S.C. § 103(a) as obvious over Faustman „346 or Faustman „689.
However, we reverse the Examiner‟s rejection of claims 65-75, under
35 U.S.C. § 102(b) as anticipated by North.

TIME PERIOD
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

alw
UNITED STATES PATENT AND TRADEMARK OFFICE
__________

BEFORE THE PATENT TRIAL AND APPEAL BOARD
__________

Ex parte WOLF-RUEDIGER SCHAEBITZ,
ARMIN SCHNEIDER, CAROLA KRUEGER, CLEMENS SOMMER,
STEFAN SCHWAB, RAINER KOLLMAR, MARTIN MAURER,
DANIELA WEBER, and NIKOLAUS GASSLER
__________

Appeal 2011-001820
Application 11/931,326
Technology Center 1600
__________

Before TONI R. SCHEINER, FRANCISCO C. PRATS, and
JACQUELINE WRIGHT BONILLA, Administrative Patent Judges.

PRATS, Administrative Patent Judge.

DECISION ON APPEAL
This appeal under 35 U.S.C. § 134 involves claims to treating
amyotrophic lateral sclerosis (ALS). The Examiner entered rejections for
anticipation and obviousness.
We have jurisdiction under 35 U.S.C. § 6(b). We affirm three of the
Examiner‟s four anticipation rejections. We also affirm the Examiner‟s
obviousness rejection.

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STATEMENT OF THE CASE
Claims 1, 20-22, and 59-75 stand rejected and appealed (App. Br. 2).
Claims 1 and 65, the independent claims, illustrate the appealed subject
matter and read as follows:
Claim 1. A method of treating amyotrophic lateral sclerosis
in a mammal, consisting of administering to the mammal in need
thereof, a hematopoietic factor selected from the group consisting of
mammalian granulocyte colony stimulating factor (G-CSF), human
G-CSF, a protein having at least 90% homology to SEQ ID NO:37
and G-CSF activity, a protein having at least 90% homology to SEQ
ID NO:38 and G-CSF activity, a protein having at least 90%
homology to SEQ ID NO:39 and GCSF activity, PEG-modified
G-CSF, or a combination thereof in an amount sufficient to treat the
amyotrophic lateral sclerosis.

Claim 65. A method of treating amyotrophic lateral sclerosis
caused by a SOD1 mutation in a mammal, comprising administering
to the mammal in need thereof, a hematopoietic factor selected from
the group consisting of mammalian granulocyte colony stimulating
factor (G-CSF), human G-CSF, a protein having at least 90%
homology to SEQ ID NO:37 and G-CSF activity, a protein having at
least 90% homology to SEQ ID NO:38 and G-CSF activity, a protein
having at least 90% homology to SEQ ID NO:39 and GCSF activity,
PEG-modified G-CSF, or a combination thereof in an amount
sufficient to treat the amyotrophic lateral sclerosis.

The following rejections are before us for review:
(1) Claims 1, 20-22, 60-68, and 70-75, under 35 U.S.C. § 102(b) as
anticipated Faustman „346
1
(Ans. 4-6);
(2) Claims 1, 20-22, 60-68, and 70-75, under 35 U.S.C. §§ 102(a) and
102(e) as anticipated by Faustman „689
2
(Ans. 6-8);

1
WO 99/43346 A1 (published September 2, 1999).
2
U.S. Patent App. Pub. No. 2002/0106689 A1 (published August 8, 2002).
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(3) Claims 1, 20-22, and 59-75, under 35 U.S.C. §§ 102(a) and 102(e)
as anticipated by Chajut
3
(Ans. 8-9);
(4) Claims 65-75, under 35 U.S.C. § 102(b) as anticipated by North
4

(Ans. 9-10); and
(5) Claims 59 and 69, under 35 U.S.C. § 103(a) as obvious over
Faustman „346 or Faustman „689 (Ans. 10-14).
ANTICIPATION – THE FAUSTMAN PUBLICATIONS
Appellants contend that “Faustman US „689 is the national stage filing
of Faustman WO „346” (App. Br. 6). While that fact is not apparent from
either publication, the relevant disclosures of Faustman „346 and Faustman
„689 do in fact appear to be substantially the same. We therefore consider
the Examiner‟s anticipation rejections over both Faustman publications
together.
As stated in In re Oetiker, 977 F.2d 1443, 1445 (Fed. Cir. 1992):
[T]he examiner bears the initial burden . . . of presenting a
prima facie case of unpatentability. . . .
After evidence or argument is submitted by the applicant
in response, patentability is determined on the totality of the
record, by a preponderance of evidence with due consideration
to persuasiveness of argument.

Appellants‟ arguments do not persuade us that a preponderance of the
evidence fails to support the Examiner‟s prima facie case that the Faustman
publications anticipate claim 1.

3
U.S. Patent App. Pub. No. 2002/0198150 A1 (published December 26,
2002).
4
Will A. North et al., Reversible Granulocytopenia in Association with
Riluzole Therapy, 34 Annals of Pharmacotherapy 322-32 (2000).
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Claim 1 recites a method of treating amyotrophic lateral sclerosis
(ALS) in a mammal. The method consists of administering a hematopoietic
factor, which may be mammalian granulocyte colony stimulating factor (G-
CSF), to the mammal in need of such treatment. The G-CSF must be
administered in an amount sufficient to treat the ALS.
Faustman „346 discloses “a method of treating an autoimmune disease
in a mammal, comprising administering to a mammal suspected of suffering
from an autoimmune disease an agent which restores NFκB activity in an
amount and for a time sufficient to result in normal NFκB activity in the
mammal” (Faustman „346 at p. 16; see also Faustman „689 at [0104]).
Faustman then discloses that, “[p]referably, the agent is selected from
the group that consists of a protein and a nucleic acid that encodes that
protein” and, further, that “[i]t is preferred that the protein is selected from
the group that includes . . . granulocyte colony-stimulating factor . . .”
(Faustman „346 at pp. 16-17; see also Faustman „689 at [0106]-[0107]).
Faustman then discloses that, “[i]n another preferred embodiment, the
autoimmune disease is selected from the group that includes those diseases
listed above” (Faustman „346 at p. 17), among which is ALS (see id. at p. 7;
see also Faustman „689 at [0112] and [0031]). Thus, as the Examiner
pointed out, Faustman describes treating the claimed disorder with the
claimed therapeutic agent.
We acknowledge, as Appellants argue, that in an anticipation rejection
“it is not enough that the prior art reference . . . includes multiple, distinct
teachings that [an ordinary] artisan might somehow combine to achieve the
claimed invention.” NetMoneyIN, Inc. v. VeriSign, Inc., 545 F.3d 1359,
1371 (Fed. Cir. 2008). Rather, the reference “must clearly and
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5
unequivocally disclose the claimed [invention] or direct those skilled in the
art to the [invention] without any need for picking, choosing, and combining
various disclosures not directly related to each other by the teachings of the
cited reference.” Id. (quoting In re Arkley, 455 F.2d 586, 587 (CCPA 1972).
We also acknowledge that Faustman lists ALS alongside about 56
other diseases that can be treated (see Faustman „346 at page 7), and that
G-CSF is listed alongside about 23 other agents that can be used to treat
those diseases (see id. at 17). However, because the specifically listed
diseases and specifically listed treating agents do not number in the
thousands, or multiple thousands, or more, we are not persuaded that
Faustman‟s description of which diseases to treat, and which agents to use,
amounts to a meaningless description of treating any of a “plethora” of
disorders, as Appellants argue (App. Br. 6).
To the contrary, because the Faustman publications lay out the
NFκB-related treatment methods in a sequential manner that evidences a
direct relationship between a list of specific “preferred” treatment agents
(see Faustman „346 at p. 16; Faustman „689 at [0107]), and a list of specific
“preferred” diseases to be treated with those agents (id. Faustman „346 at 17;
Faustman „689 at [0112]), we agree with the Examiner that improper picking
and choosing of unrelated disclosures is not required to “at once envisage”
claim 1‟s treatment of ALS with G-CSF. See In re Petering, 301 F.2d 676,
681 (CCPA 1962) (chemical compounds held anticipated where reference
disclosing generic formula also included preferences for claimed
substituents).
Further, we are not persuaded that Appellants have advanced evidence
adequately demonstrating that the Faustman publications did not enable an
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6
ordinary artisan to treat ALS with G-CSF. We note the disclosures in Silani
5

and Jackson
6
that the hypothesized link between autoimmunity and ALS is
waning in popularity, as well as the disclosures in Jackson and Jerusalem
7

that attempts at treating ALS with immunologically-based had been
unsuccessful (see Silani at p. 25 (abstract); Jackson at p. 34; Jerusalem at p.
S218).
As Appellants point out, however, “in the context of a claimed
method for treating a disease, a prior art reference need not disclose „proof
of efficacy‟ to anticipate the claim.” In re Gleave, 560 F.3d 1331, 1335
(Fed. Cir. 2009) (citing Impax Labs., Inc. v. Aventis Pharms. Inc., 545 F.3d
1312, 1314 (Fed. Cir. 2008); Rasmusson v. SmithKline Beecham Corp., 413
F.3d 1318, 1326 (Fed. Cir. 2005)).
Thus, the fact that autoimmunity might not be the most popular
causative hypothesis for ALS among those skilled in the art does not provide
sufficient clear or specific evidence to persuade us that an ordinary
practitioner, armed with Faustman‟s disclosure of treating ALS with G-CSF,
would have been able to practice Faustman‟s method only through undue
experimentation.
Therefore, as Appellants‟ arguments do not persuade us that the
Examiner erred in maintaining the anticipation rejection of claim 1 over the
Faustman publications, we affirm the Examiner‟s rejections of that claim

5
Vincenzo Silani et al., Patogeneza SLA: implikacje dla leczenia, NEUR.
NEUROCHIR. POL. Supp.I 25-39 (2001).
6
Carlayne E. Jackson and Wilson W. Bryan, Amyotrophic Lateral Sclerosis,
18 SEMINARS IN NEUROLOGY 27-39 (1998).
7
F. Jerusalem et al., ALS, 47 NEUROLOGY Suppl. 4 S218-S220 (1996).
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over those references. As they were not argued separately, claims 20-22 and
60-64 fall with claim 1. See 37 C.F.R. § 41.37(c)(1)(vii).
Appellants‟ arguments also fail to persuade us that the Examiner erred
in maintaining the anticipation rejections over the Faustman publications as
to claim 65. Claim 65, like claim 1, encompasses treating mammals having
ALS with G-CSF, but limits the treated subjects to those having ALS
“caused by a SOD1 mutation” (App. Br. 17).
We note Silani‟s disclosure that the SOD1 mutation in the superoxide
dismutase gene is observed in a subset of ALS sufferers:
Besides the free radical hypothesis raised by the identification
of Superoxide Dismutase 1 mutations in a subset of familiar
Amyotrophic Lateral Sclerosis (ALS) patients, three
etiopathogenic hypotheses for sporadic ALS, namely
autoimmune, neurofilament, and glutamate toxicity, have
attracted interest in the last few years. The role of
autoimmunity in ALS has been seriously questioned.

(Silani at p. 25.) We also note Appellants‟ assertion that, in their hands,
G-CSF exhibited a trend toward increasing life expectancy in a transgenic
mouse model of ALS that includes an SOD1 mutation (see, e.g. Spec. 163
(Example 33)).
Appellants have not, however, advanced clear or specific evidence
suggesting that, despite the fact that they suffer from the same disorder, the
subset of ALS sufferers exhibiting the SOD1 mutation would have been
viewed sufficiently differently from ALS sufferers generally, such that an
ordinary artisan viewing Faustman‟s disclosure of treating ALS with G-CSF
would have failed to envisage treating the SOD1-carrying patients with that
agent. Thus, as Appellants‟ arguments do not persuade us that the Examiner
erred in maintaining the anticipation rejections of claim 65 over the
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Faustman publications we affirm those rejections as well. Claims 66-68 and
70-75 fall with claim 65. See 37 C.F.R. § 41.37(c)(1)(vii).
OBVIOUSNESS – THE FAUSTMAN PUBLICATIONS
Claims 59 and 69 depend, respectively, from claims 1 and 65, and
both require the hematopoietic factor, which may be G-CSF, to be
administered daily (see App. Br. 16 (claim 59); see also id. at 18 (claim 69)).
While the Examiner conceded that the Faustman publications did not
describe daily administration of G-CSF, the Examiner reasoned that an
ordinary artisan practicing Faustman‟s ALS treatment would have
considered it obvious to “modify the teachings of Faustman by formulating a
daily dosage regimen, because both Faustman disclosures clearly provide
guidance to one of ordinary skill in the art as to how to formulate treatment
regimens for proteins” (Ans. 13).
In traversing this rejection, Appellants rely solely on their previous
arguments directed to the anticipation rejection (see App. Br. 11 (“[A]s
discussed above, Faustman does not actually disclose the treatment of ALS
in the manner that is claimed and as such Faustman cannot render Claim 59
obvious.”)).
Thus, as Appellants point to no specific deficiency as to the
Examiner‟s prima facie case of obviousness, and as we are not persuaded,
for the reasons discussed above, that the Examiner erred in maintaining the
anticipation rejection, we affirm the Examiner‟s obviousness rejections over
the Faustman publications.

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ANTICIPATION – CHAJUT
The Examiner rejected claims 1, 20-22, and 59-75, all of the pending
claims, as anticipated by Chajut under 35 U.S.C. §§ 102(a) and 102(e) (see
Ans. 8-9).
Appellants do not argue any of the claims subject to this ground of
rejection separately (see App. Br. 11-13). We select claim 1 as
representative of the rejected claims. See 37 C.F.R. § 41.37(c)(1)(vii).
Appellants‟ arguments do not persuade us that a preponderance of the
evidence fails to support the Examiner‟s prima facie case that Chajut
anticipates claim 1.
Chajut discloses the use of “growth factors that stimulate migration
and differentiation of stem cells, particularly colony stimulating factors
(CSFs), in order to promote and enhance recovery from tissue trauma and
ischemic events, including ischemia of the central nervous system, as well as
for use in preventing or diminishing chronic degenerative changes” (Chajut
[0024]).
Chajut then states:
The compositions of the present invention may also be
effective in treating certain chronic degenerative diseases that
are characterized by gradual selective neuronal loss. In this
connection, the compositions of the present invention are
contemplated as therapeutically effective in the treatment of
Parkinson‟s disease, Alzheimer‟s disease, epilepsy, depression,
ALS (Amyotrophic lateral sclerosis), Huntington‟s disease and
any other disease-induced dementia (such as HIV-induced
dementia, for example).
These effects will be achieved by administering an agent
that stimulates the mobilization of bone marrow-derived stem
cells into the bloodstream. Representative agents useful in the
methods of the invention include, for example, granulocyte-
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colony stimulating factor (G-CSF), granulocyte-macrophage-
colony stimulating factor (GM-CSF), stem cell factor (SCF),
interleukin-3 (IL-3) and interleukin-6 (IL-6). These factors have
all been shown to be capable of mobilizing bone marrow-
derived stem cells . . . .

(Chajut [0027]-[0028] (emphases added, citations omitted).)
We acknowledge that, in addition to ALS, Chajut lists additional
disorders that may be treated according to its methods. We also
acknowledge that, in addition to G-CSF, Chajut lists a number of other
therapeutic agents that may be used to treat those disorders. However, given
the sequential and related manner in which Chajut presents the treated
disorders and the treating agents, as well as the limited number of choices of
both, Appellants‟ arguments do not persuade us that Chajut fails to
adequately describe, in the manner required under § 102, claim 1‟s process
of treating ALS with G-CSF.
Appellants argue that Chajut does not demonstrate, by presentation of
a working example, infiltration of stem cells activated by G-CSF into the
central nervous system (see App. Br. 11-12). Appellants argue that the
disclosures of Chen
8
and Smith
9
similarly cast doubt on whether an ordinary
artisan would have reasonably expected that the mechanism of action
proposed by Chajut would provide an effective treatment of ALS (see id. at
13).

8
Jieli Chen et al., Therapeutic Benefit of Intravenous Administration of Bone
Marrow Stromal Cells After Cerebral Ischemia in Rats, 32 STROKE 1005-
1011 (2001).
9
Richard A. Smith et al., Pharmacokinetics and tolerability of ventricularly
administered superoxide dismutase in monkeys and preliminary clinical
observations in familial ALS, 129 J. NEUR. SCI. (Suppl.) 13-18 (1995).
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We are not persuaded. We note, in an experiment which assessed the
therapeutic effect of intravenously administered stem cells, that Chen
posited that “[d]isruption of the blood-brain barrier may facilitate selective
entry of [stem cells] into ischemic brain compared with nonischemic
contralateral cerebral tissue” (Chen at p. 1010). We also note that, because
of the presence of the blood-brain barrier, Smith evaluated direct central
nervous system administration of the superoxide dismutase protein as a
potential treatment for ALS (see Smith at p. 14).
Appellants do not, however, point to any clear or specific teaching in
Chen or Smith that directly discusses the methods described in Chajut.
Moreover, as noted above, “in the context of a claimed method for treating a
disease, a prior art reference need not disclose proof of efficacy to anticipate
the claim.” In re Gleave, 560 F.3d at 1335 (internal quotations removed).
Consistently, in Rasmusson v. SmithKline Beecham, for example, the
Federal Circuit reversed the BPAI‟s conclusion that a reference describing a
cancer treatment was not enabled for anticipation purposes, despite the fact
that the Board had based its non-enablement conclusion upon findings
supporting the premise that an ordinary artisan would not have believed that
the method described in the reference would be effective, as well as the fact
that the reference itself lacked proof of efficacy. See Rasmusson, 413 F.3d
at 1326.
We are therefore not persuaded that Appellants have advanced
evidence adequately demonstrating that the method of treating ALS with
G-CSF described in Chajut is not enabled for anticipation purposes.
Accordingly, as Appellants‟ arguments do not persuade us that the Examiner
erred in maintaining the anticipation rejection of claim 1 over Chajut, we
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affirm that rejection. Claims 20-22 and 59-75 fall with claim 1. See 37
C.F.R. § 41.37(c)(1)(vii).
ANTICIPATION – NORTH
The Examiner also rejected claims 65-75 under 35 U.S.C. § 102(b) as
anticipated by North (Ans. 9-10).
As Appellants point out, and as pointed out above, claim 65
encompasses treating mammals having ALS with G-CSF, but limits the
treated subjects to those having ALS “caused by a SOD1 mutation” (App.
Br. 17).
In this instance, we agree with Appellants that a preponderance of the
evidence does not support the Examiner‟s prima facie case of anticipation.
In particular, we are not persuaded that the Examiner has advanced
sufficient evidence to support a finding that the patient treated in North
inherently suffered from ALS caused by an SOD1 mutation, as claim 65
requires.
It is well settled in the law of anticipation that the “very essence of
inherency is that one of ordinary skill in the art would recognize that a
reference unavoidably teaches the property in question.” Agilent
Technologies, Inc. v. Affymetrix, Inc., 567 F.3d 1366, 1383 (Fed. Cir. 2009)
(emphasis added); see also In re Oelrich, 666 F.2d 578, 581 (CCPA 1981)
(“Inherency, however, may not be established by probabilities or
possibilities. The mere fact that a certain thing may result from a given set
of circumstances is not sufficient.”).
Thus, if “the disclosure is sufficient to show that the natural result
flowing from the operation as taught would result in the performance of the
questioned function, it seems to be well settled that the disclosure should be
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regarded as sufficient.” Oelrich, 666 F. 2d at 581 (quoting Hansgirg v.
Kemmer, 102 F.2d 212, 214 (CCPA 1939)).
Here, North describes treating a single ALS patient with filgramstim
(North 322, abstract), which is undisputed on this record to be a
“pharmaceutical version of G-CSF” (Ans. 3). North explains that the ALS
patient experienced granulocytopenia as an apparent side effect of the
riluzole that was being administered to treat the ALS (North 322, abstract).
North reported that “[b]lood counts returned to normal with discontinuation
of riluzole and administration of filgramstim” (id.).
However, as pointed out in Silani, only a subset of ALS sufferers has
the SOD1 mutation (see Silani 25 (abstract)). Thus, because the Examiner
has pointed to no evidence supporting a finding that North‟s patient
necessarily had the SOD1 mutation, the evidence of record at best shows
that there was a possibility that North‟s patient had the SOD1 mutation.
As noted above, however, inherency may not be established by
probabilities or possibilities. In re Oelrich, 666 F.2d at 581.
The Examiner argues that “[w]hether a person develops ALS because
of a SOD1 mutation or glutamate toxicity is a distinction without a
difference. The person of ordinary skill in the art, as evidenced by Smith et
al. above, would not differentiate in his or her treatment between a patient
with FALS [familial ALS] or ALS (Ans. 41).
We acknowledge the statement in Smith (a different reference) cited
by the Examiner: “[T]he similar clinical course and histopathology of
sporadic ALS and FALS, whether or not there is an SOD gene mutation,
suggest that common molecular mechanisms, and hence a common approach
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to treatment, may apply to all forms of this devastating disease” (Smith 13
(citation omitted).
We also acknowledge that this statement supports a finding that an
ordinary artisan would have understood that a generic description of treating
ALS would not differentiate between patients exhibiting different
hypothetical causative factors, such as SOD1 mutation.
Unlike the Faustman and Chajut rejections discussed above, however,
the Examiner points to no disclosure in North that describes treating ALS
sufferers, as a generic class of patients, with G-CSF. Rather, as also noted
above, North describes treating a single patient, and the Examiner points to
no evidence suggesting that patient was necessarily a member of the subset
of ALS sufferers having the SOD1 mutation.
Accordingly, as we are not persuaded that the Examiner has advanced
adequate evidence to support a finding that the sole patient treated in North
necessarily had ALS caused by an SOD1 mutation as required by claim 65,
we reverse the Examiner‟s rejection of that claim, and its dependents over
North.
SUMMARY
We affirm the Examiner‟s rejection of claims 1, 20-22, 60-68, and 70-
75, under 35 U.S.C. § 102(b) as anticipated Faustman „346.
We also affirm the Examiner‟s rejection of claims 1, 20-22, 60-68,
and 70-75, under 35 U.S.C. §§ 102(a) and 102(e) as anticipated by Faustman
„689.
We also affirm the Examiner‟s rejection of claims 1, 20-22, and 59-
75, under 35 U.S.C. §§ 102(a) and 102(e) as anticipated by Chajut.
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We also affirm the Examiner‟s rejection of claims 59 and 69, under 35
U.S.C. § 103(a) as obvious over Faustman „346 or Faustman „689.
However, we reverse the Examiner‟s rejection of claims 65-75, under
35 U.S.C. § 102(b) as anticipated by North.

TIME PERIOD
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

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