Ex Parte Gelmont et al

Patent Trials and Appeals Board

Apr 30, 2019

14270192 - (D) (P.T.A.B. Apr. 30, 2019)

UNITED STA TES p A TENT AND TRADEMARK OFFICE
APPLICATION NO. FILING DATE
14/270,192 05/05/2014
12139 7590 05/02/2019
Morgan, Lewis & Bockius LLP (SF)(Baxter)
ONE MARKET, SPEAR STREET TOWER
SAN FRANCISCO, CA 94105
FIRST NAMED INVENTOR
David M. Gelmont
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
ATTORNEY DOCKET NO. CONFIRMATION NO.
008073-5091-US 3005
EXAMINER
FONTAINHAS, AURORAM
ART UNIT PAPER NUMBER
1649
NOTIFICATION DATE DELIVERY MODE
05/02/2019 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):
SFIPDOCKETING@MORGANLEWIS.COM
donald.mixon@morganlewis.com
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
BEFORE THE PATENT TRIAL AND APPEAL BOARD
Ex parte DAVID M. GELMONT, WLIA SINGER, SANDOR FRITSCH,
and HANS-PETER SCHWARZ
Appeal2018-002497
Application 14/270, 192 1
Technology Center 1600
Before ERICA A. FRANKLIN, ELIZABETH A. LA VIER, and
RACHEL H. TOWNSEND, Administrative Patent Judges.
TOWNSEND, Administrative Patent Judge.
DECISION ON APPEAL
This is an appeal under 35 U.S.C. § 134 involving claims to a method
for treating Alzheimer's disease, which have been rejected as anticipated and
obvious. We have jurisdiction under 35 U.S.C. § 6(b).
We reverse the Examiner's anticipation rejection but affirm that the
claims are rendered obvious by the cited prior art.
1 Appellants, which are the Applicants Baxter International Inc., and Baxter
Healthcare SA, identify the real parties in interest as Baxalta GMBH and
Baxalta Inc., both of which are described as wholly-owned subsidiaries of
Shire plc. (Appeal Br. 4.)
Appeal2018-002497
Application 14/270, 192
STATEMENT OF THE CASE
"Alzheimer's disease (AD) is a progressive neurodegenerative
disorder." (Spec. ,r 2.) "[S]everal studies have suggested that pooled
intravenous immunoglobulin (IVIG) is effective in slowing the progression
of symptoms in Alzheimer's patients." (Id. ,r 8.) Appellants' invention is
directed at a method of treating AD patients with high dose IVIG. (Id.
,r,r 17-18.)
Claims 79, 82, 83, 105, 111, 114, 115, 117-119, and 121-123 are on
appeal. Claim 79 is representative and reads as follows:
79. A method for treating Alzheimer's disease in a subject in
need of treatment thereof, the method comprising:
(a) diagnosing the severity of Alzheimer's disease in the
subject as mildly severe, moderately severe, or severe, wherein
a diagnosis of moderately severe Alzheimer's disease
corresponds to a Mini-Mental Status Examination (MMSE)
score of from 14 to 22;
(b) determining if the subject carries an APOE4 allele;
and
( c) in response to the diagnosing in step (a) and
determining in step (b ):
in accordance with a diagnosis of moderately severe
Alzheimer's disease and a determination that the subject carries
an APOE4 allele, administering a therapeutically effective
amount of a composition comprising pooled human
immunoglobulin G (IgG) to the subject, wherein the amount of
pooled human IgG is from 300 mg/kg to 800 mg/kg body
weight of the subject per two week period, and wherein the
amount is administered in one or more doses during the two
week period after initiation of a therapeutic regimen; and
in accordance with either a diagnosis that is not
moderately severe Alzheimer's disease or a determination that
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the subject does not carry at least one APOE4 allele, forgo
administering a composition comprising pooled human
immunoglobulin G (IgG) to the subject.
(Appeal Br. 40.)
The following grounds of rejection by the Examiner are before us on
review:
Claims 79,105,111,114,115, 117-119,and 12I-123under35
U.S.C. § I02(a)(l) as anticipated by Relkin2 as evidenced by Alz.org3 and
Lovell. 4
Claims 79, 82, 83, 105, 111, 114, 115, 117-119, and 121-123 under
35 U.S.C. § 103 as unpatentable over Relkin as evidenced by Alz.org and
Lovell.
DISCUSSION
Relkin Teaches Treating Patients Within the Claimed Class But Does Not
Anticipate the Claimed Method
The Examiner finds that "[t]he claimed method requires only the
administration of a therapeutically effective amount of pooled human lgG to
a subject diagnosed as having AD ( defined as corresponding to a MMSE
score of 14--22) and carrying at least one APOE4[5J allele." (Ans. 3.) Thus,
2 Relkin, US 2011/0251479 Al, published Oct. 13, 2011.
3 Tests for Alzheimer's Disease and Dementia, Alz.org,
https :// alz. org/ alzheimers-dementia/ diagnosis/medical_tests (last visited:
Apr. 29, 2019).
4 Lovell et al., WO 2011/142778 Al, published Nov. 17, 2011.
5 APOE is apolipoprotein E. (Spec. ,i 4.) The amyloid beta (AB) peptide "is
known to spontaneously form soluble aggregates called oligomers and
insoluble fibrils that can form deposits in the brain." (Id. ,i 6.) Different
APOE isoforms can modulate AB levels. (Id. ,i 14)
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Application 14/270, 192
according to the Examiner, "so long as at least one subject having these
criteria (AD, MMSE score of 14--22, APOE4 carrier) has been treated
according to the active step of administering IgG in one or more doses at
300 mg/kg to 800 mg/kg body weight during a two week treatment period,
then the presently recited method has been performed and therefore
anticipated." (Id.) The Examiner finds Relkin teaches such an
administration in Example 1, where pooled human IgG at doses of 400 or
800 mg/kg body weight once per two weeks was administered to patients.
(Id.; Final Action 3--4.) The Examiner notes that "the patient population
[treated with pooled human IgG] was previously diagnosed with
Alzheimer's disease and [was] already being treated with AChE inhibitors
and N amenda," their diagnosis of mild to moderate AD was determined by
MMSE score of 14--26, and 79% of the treatment group "were diagnosed as
APOE E4 carriers." (Final Action 3--4.)
The Examiner notes that the language in the final phrase of claim 79
stating that the decision not to give IVIG is made "'in accordance with either
a diagnosis that is not moderately severe Alzheimer's disease or a
determination that the subject does not carry at least one APOE4 allele'
( emphasis added) means that only one of these considerations must be taken
into account to exclude administration of the composition to such a subject."
(Ans. 4--5; Final Action 6.) The Examiner finds that Relkin excludes
treating subjects that fall within the MMSE 0-13 range, as well as those
without a cognitive deficit, i.e. the MMSE range of 27-30. (Ans. 4; Final
Action 5-6 ("Relkin clearly teaches all the required limitations of
identifying the instantly claimed patient population since Relkin's MMSE
scores does exclude the treatment of certain Alzheimer's patients with a
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MMSE score ranging from 0-13 (severe deficit) and subjects without a
cognitive deficit (27-30).").) The Examiner explains that "Relkin does not
administer IVIG to patients who do not have moderately severe AD, and
therefore implicitly teaches the limitations of the presently claimed
methods." (Id.)
We disagree with the Examiner's claim interpretation and factual
finding that led to the Examiner's conclusion that Relkin anticipates claim
79.
In particular, as Appellants note (Appeal Br. 12, Reply Br. 3--4), the
method of claim 79 requires three distinct steps, the third of which builds on
the first two, and is not a method of simply administering IgG to a patient
that happens to fall in the population claimed, as contended by the Examiner
(Ans. 3 ("so long as at least one subject having these criteria (AD, MMSE
score of 14--22, APOE4 carrier) has been treated according to the active step
of administering IgG in one or more doses at 300 mg/kg to 800 mg/kg body
weight during a two week treatment period, then the presently recited
method has been performed and therefore anticipated").)
First, a diagnosis of the severity of AD in a patient must be made
using the MMSE and a determination of whether the subject carries an
APOE4 allele is made. Based on the diagnosing step and determining step
made ("in response to"), a person carrying out the method must determine
what particular administration regime is carried out ("in accordance with").
If a subject has been determined to have moderately severe AD and carries
an APOE4 allele, then IVIG is administered from 300 to 800 mg/kg body
weight per two week period. If the subject is determined to only have one of
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the foregoing conditions, then no IVIG is administered. This is not what is
taught by Relkin.
We agree with the Examiner that Relkin teaches administering the
claimed therapeutically effective amount of IgG to a patient population that
meets the claimed criteria. (Relkin ,r,r 45--48 (Example describing the IVIG
Phase 2 clinical trial "testing safety and utility/futility of IVIG treatment" for
AD in 24 patients).) In the Phase 2 study described, 24 patients that had an
MMSE score of 14--26 were given IVIG. (Id. ,r 46.) We note that an
MMSE score between 14--26 encompasses the claimed range of an MMSE
score of 14--22.
As the Examiner pointed out, Lovell Table 1 shows that it was well
known that certain MMSE score ranges were generally understood to
represent degrees of cognitive function. (Ans. 3--4.) In particular, MMSE
scores between 21-26 represent mild cognitive impairment, whereas 11-20
represents moderate cognitive impairment, and 0-10 represent severe
cognitive impairment, while 27-30 represent normal cognitive function.
(Lovell ,r 162.) While Appellants' claim contends the patient to be treated
with IVIG has moderately severe AD, the MMSE score of between 14--22
indicates the cognitive impairment could be mild or moderate. Likewise, the
subjects that were treated in Relkin's Phase 2 study had an MMSE between
mild to moderate cognitive impairment.
Moreover, in Relkin's described Phase 2 study, 79% of the patients
that were diagnosed with AD and had mild to moderate cognitive
impairment based on an MMSE scored between 14--26, and were treated
with IVIG, also were determined to carry the APOE4 allele. (Relkin ,r 48,
Table 1.)
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However, we agree with Appellants that Relkin does not teach the
claimed method was carried out, i.e., administration of, or foregoing the
administration of IVIG, in response to the MMSE assessment determination
and whether the subject was an APOE4 carrier. That this is true is borne out
by the fact that 21 % of the subjects that received IVIG in Relkin's described
Phase 2 study were not an APOE4 carrier. (Relkin ,r 48, Table 1.) Thus,
while Relkin teaches a population of subjects that had the claimed
characteristics were treated with IVIG within the claimed dosage amount, it
does not teach the diagnosing and determining steps of the claim were
performed and, in response to those steps and in accordance with the results,
only those meeting the diagnostic requirements set forth in steps a and b
were treated with IVIG. Accordingly, we reverse the Examiner's rejection
of claim 79, and claims dependent thereon, as being anticipated by Relkin.
Relkin Renders Obvious the Claimed Method
It is apparent that Appellants consider the Examiner to have rejected
claims 79, 105, 111, 114, 115, 117-119, and 121-123 as being obvious over
Relkin, as reflected by their arguments. (Appeal Br. 18-37.) We, therefore,
consider the rejection and the arguments from the same perspective, i.e., that
the Examiner rejected all of claims 79, 82, 83, 105, 111, 114, 115, 117-119,
and 121-123 as being obvious over Relkin.
Having considered the evidence and arguments, including the asserted
evidence of unexpected results, we conclude that Relkin renders claim 79
obvious. As discussed above, Relkin teaches treating patients with IVIG
who have been determined to have an MMSE of 14--26 and to carry the
APOE4 allele.
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Relkin concludes, based on the Phase 2 study discussed above in
which patients that had AD and an MMSE score between 14--26, with or
without APOE E4, had positive results with IVIG treatment. (Relkin ,r,r 49-
52, 55.) In particular, Relkin states that "[u]ninterrupted IVIG treatment of
AD patients for 18 months resulted in significantly better outcomes on the
CGIC, ADAS-Cog, ADL and NPI scales6 compared to initial placebo
treatment." (Relkin ,r 55.) Relkin also teaches that patients who should
receive IVIG according to the method of the invention should typically be
"in the relatively early stages of the disease progression with mild to
moderate symptoms." (Relkin ,r 36.) As Relkin explains, in such patients,
"their improvement from the therapeutic agent will be easier to determine
and thus their future treatment plan can be properly adjusted." (Id.)
Given the positive results identified in the Phase 2 study described by
Relkin with patients who were both APOE E4 positive and had an MMSE
score between 14--26, we conclude that it would have been obvious to
determine an AD patient's MMSE score and APOE E4 status ab initio to
determine whether they would be a good candidate for IVIG treatment at the
dosage range described by Relkin's Phase 2 study to provide improvement.
As the Examiner noted (e.g., Final Action 6), claim 79 provides for a non-
treatment decision to be made where a patient "either" is not determined to
have moderately severe AD, i.e., is outside of the 14--26 MMSE range, "or"
does not carry at least one APOEE4 allele. We conclude that after
6 ADAS-Cog is the Alzheimer's Disease Assessment Scale-Cognitive
Subscale; ADL is Activities of Daily Living; NPI is Neuropsychiatric
Inventory (Relkin ,r 48 Table 2.) CGIC stands for Clinical Global
Impression of Change. (See, e.g., Spec. ,r 152.)
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undertaking the analysis of a patient's MMSE score and APOE E4 status, a
person of ordinary skill in the art would have been motivated by Relkin to
treat those patients whose MMSE score fell in the range of 14--26, and had
an APOE E4, with IVIG 0.8 g/kg once per 4 weeks and 0.4 g/kg with a
reasonable expectation of achieving a therapeutic result but choose not to
treat those patients determined to have an MMSE score above 26 or below
14. While it is true that the MMSE range for which treatment would be
made is broader in Relkin (14--26) than what is claimed (14--22), we note
that "[a] primafacie case of obviousness typically exists when the ranges of
a claimed composition overlap the ranges disclosed in the prior art .... In
fact, when ... the claimed ranges are completely encompassed by the prior
art, the conclusion is even more compelling than in cases of mere overlap.
The normal desire of scientists or artisans to improve upon what is already
generally known provides the motivation to determine where in a disclosed
set of percentage ranges is the optimum combination of percentages." In re
Peterson, 315 F.3d 1325, 1329-30 (Fed. Cir. 2003).
Appellants argue that a skilled artisan would not have been motivated
to treat patients with an MMSE score of from 14--22 based upon the
teachings of Relkin because "Relkin contemplates treating any Alzheimer's
patient, regardless of disease severity or APOE4 status, with IVIG."
(Appeal Br. 19; see also id. 21-22 ("Any selection of a particular subset of
Alzheimer's patients for IVIG therapy in Relkin is solely a consequence of
Relkin's monitoring and adjustment methodology, which requires easy
detection of improvements in the subject's symptoms.").) We disagree with
Appellants' premise.
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Relkin teaches selecting patients with moderate to moderately severe
symptoms as the improvement will be easier to determine and to properly
adjust their future treatment plan (Relkin ,r 36) and demonstrates positive
outcomes result with respect to patients that have mild to moderate cognitive
impairment (MMSE 14--26) and APOE E4. Relkin explains the "[ s ]ubjects
who responded to IVIG at 18 months performed significantly better than
nonresponders in language functioning and construction and on tests of
executive function, including attention, working memory, conceptualization,
and verbal fluency tasks." (Relkin ,r 55.) Thus, Relkin reasonably suggests
treatment of a particular subset of Alzheimer patients, patients that have
mild to moderate cognitive impairment (MMSE 14--26). While this range
includes four more MMSE scores of mild cognitive impairment than
claimed (23-26), as discussed above the range claimed is fully embraced
and rendered obvious by the treatment group in Relkin. While Relkin did
not seem to take into consideration, in the phase 2 study, the APOE4 status
prior to treatment ( as noted above), the results achieved in that
subpopulation would have suggested to one of ordinary skill in the art to
treat patients that had that characteristic along with having an MMSE score
between 14--26 with IVIG, and that they would have had a reasonable
expectation of success in such a treatment.
Appellants further contend that "because Relkin fails to single out any
particular subset of Alzheimer's patients for which pooled human IgG
therapy would be more or less effective .... there would have been no
reason for the person having ordinary skill in the art to limit pooled human
IgG administration exclusively to the subset of Alzheimer's patients recited
in Appellants' claim 79." (Appeal Br. 24.) We do not find this argument
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persuasive because Relkin suggests the desirability of treating a
subpopulation of AD patients that have an MMSE score between 14--26
( which includes those AD patients that have an MMSE score between 14--
22), and are APOE4 carriers with IVIG because "[ u ]ninterrupted IVIG
treatment of [those] AD patients for 18 months resulted in significantly
better outcomes on the CGIC, ADAS-Cog, ADL and NPI scales compared
to initial placebo treatment." (Relkin ,r 55.) Whether treatment of the AD
patients with MMSE scores between 14--22 is suggested by Relkin to be
more efficacious than in the broader 14--26 population or whether Relkin
suggests the treatment is more efficacious for those who are APOE4 carrier
compare to those who are not an APOE4 carrier is not determinative as to
the propriety of the obviousness of the claimed invention. That is because
"the question is whether there is something in the prior art as a whole to
suggest the desirability, and thus the obviousness, of making the
combination, not whether there is something in the prior art as a whole to
suggest that the combination is the most desirable combination available."
In re Fulton, 391 F.3d 1195, 1200 (Fed. Cir. 2004) (citation omitted).
That Appellants found the treatment to be "an effective therapy for
subjects diagnosed with moderately severe Alzheimer's disease who also
carry an[] APOE4 allele" (Appeal Br. 28), which is a particular
subpopulation that was also treated in Relkin does not establish non-
obviousness. "Scientific confirmation of what was already believed to be
true may be a valuable contribution, but it does not give rise to a patentable
invention." PharmaStem Therapeutics, Inc. v. ViaCell, Inc., 491 F.3d 1342,
1363---64 (Fed. Cir. 2007). Relkin established more than a belief of
effectiveness in the claimed population, it in fact established treatment
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effectiveness within the claimed population, even if that was not the aim of
the study (Appeal Br. 20-21 ("Relkin is not concerned with the selection of
a subset of Alzheimer's patients for which IVIG therapy will be particularly
effective but, rather, on how Alzheimer's therapy can be tailored to improve
the benefits of an ongoing therapeutic regime."); Appeal Br. 22 ("Relkin's
focus [is] on monitoring and adjusting therapy for Alzheimer's disease")).
The only difference being that Relkin did not make its decision to treat in the
first place in the Phase 2 study described because the patient population had
all of the claimed characteristics. But given the study outcome, there can be
no doubt that Relkin provides a significant reason to treat a patient
determined to fit within the population identified as having benefitted, e.g.,
MMSE 14--26, APOE E4 positive (as well as APOE E4 negative).
Appellants argue that Relkin includes patients specifically excluded
by claim 79, i.e., patients with MMSE score from 23 to 26. (Appeal Br. 23.)
We agree. However, that fact does not avoid a finding of prima facie
obviousness in light of the overlap of the claimed range. "Selecting a
narrow range from within a somewhat broader range disclosed in a prior art
reference is no less obvious than identifying a range that simply overlaps a
disclosed range." In re Peterson, 315 F.3d at 1329-30.
Appellants also argue that the broad genus disclosed in Relkin does
not obviate the specific claimed species. (Appeal Br. 33-34.) This
argument is not found persuasive as it does not take into account the very
specific teaching of the phase 2 study described in Relkin where the
population treated had both an MMSE within the range claimed and was at
least in large part APOE E4 positive, as discussed above. Thus, contrary to
Appellants' assertion (Appeal Br. 34), there is very specific guidance as to a
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subset of patients that would clearly benefit from the IVIG treatment
disclosed, which subset falls squarely within the characteristics set forth in
claim 79.
Contrary to Appellants' arguments (Appeal Br. 36-37), we do not find
the facts here to be so different from Prometheus Laboratories v. Roxane
Laboratories, 805 F.3d, 1092 (Fed. Cir. 2015), to warrant a different
outcome than in that case. Relkin teaches treating AD patients that would be
classified as having moderate to mild cognitive deficit using the MMSE,
e.g., 14--26 is within the 11-26 MMSE range for moderate to mild cognitive
deficit. (See Lovell ,r 162 (Table 1 ).) Moreover, Relkin teaches that those
patients within that range and also being APOE E4 positive had positive
cognitive results at 18 months particularly when treated with IVIG at 0.4
g/kg/2 W. (See e.g., Relkin ,r 55.) The only difference between that
showing and what is claimed is a narrower MMSE treatment group, i.e., an
MMSE score of between 14--22, which, like Relkin's treatment group, is a
range that includes both those with moderate and mild cognitive impairment.
Thus, it would have been obvious from the teachings of Relkin to treat this
somewhat narrower group of patients and expect to obtain the same positive
cognitive results.
Thus, for the foregoing reasons, we find that a prima facie case of
obviousness based on Relkin exists as to claim 79.
The Data Presented in the Specification Do Not Establish Nonobviousness
Relkin demonstrates a change in 3MS, ADAS-cog, CGIC, ADL, and
NPI for its infusions of at least 0.8 g/kg once per 4 weeks and 0.4 g/kg once
per 4 weeks compared to placebo in patients that were both MMSE 14--26
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and APOE E4 positive (as well as negative). (Relkin Figures 12, 7, 5, 9, 10,
respectively; see also id. ,r,r 49-52.) In short, Relkin's phase 2 study
demonstrated patients with an MMSE score between 14--26 and who carry
APOE4 benefit in relevant cognitive measures of dementia from IVIG at 400
mg/kg/2 week. (Relkin ,r,r 50-52, 55.) Relkin's phase 2 study results are
consistent with what Appellants' Specification reports. In particular,
Appellants note that:
Overall, treatment of Alzheimer's patients by administration of
400 mg/kg/2 week IVIG resulted in reduced progression of
dementia, measured by modified mini-mental state examination
(3MS) analysis, as compared to administration of placebo
(p 1 =0.206) and administration of 200 mg/kg/2 week IVIG
(Figure 4).
(Spec. ,r 231.) The patients that were evaluated according to the
specification had AD with MMSE "mild ( defined as MMES 21-26) to
moderate (defined as MMSE 16-20)." (Id. ,r 224.)
Appellants contend that they "unexpectedly discovered that therapy
with pooled human IgG is effective to reduce progression of Alzheimer's
disease in patients diagnosed with moderately severe Alzheimer's disease
who carry an APOE4 allele, but not in the general Alzheimer's population,
in Alzheimer's patients diagnosed with mild Alzheimer's disease, or in
Alzheimer's patients who do not carry an APOE4 allele." (Appeal Br. 25.)
While it may be true that Appellants discovered the subpopulation of
Alzheimer patients with an MMSE score of 16-20 who carry APOE E4 had
a slowdown of dementia progression after administration of IVIG at 400
mg/kg/2 week, Appellants have not explained persuasively how that
discovery demonstrates unexpected results as compared to what is
demonstrated in Relkin. In other words, Appellants have not established that
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its results would not have been expected from what was known in the art, as
such results are consistent. Expected beneficial results are not evidence of
nonobviousness. See In re Skoner, 517 F.2d 947,950 (CCPA 1975).
Moreover, even Appellants' Specification indicates that progression
of AD was reduced in a broader range of AD patients, than what is claimed,
i.e., reduced progression was observed in treatment of AD patients with
MMSE scores between 16-26. (Spec. ,r,r 224, 231.) As discussed above, it
is understood in this art that AD patients with an MMSE score of 21-26
have mild cognitive impairment, where those with an MMSE score of 11-20
have moderate cognitive impairment. (Lovell ,II 62 (Table 1 ). ) Thus,
Appellants' Specification belies the assertion (Appeal Br. 25) that it is
"unexpected" that therapy with pooled human IgG is effective to reduce
progression of Alzheimer's disease in patients diagnosed with moderately
severe Alzheimer's disease who carry an APOE E4 allele, but does not
reduce progression in Alzheimer's patients diagnosed with mild AD.
Appellants' Specification also indicates that the "data indicate that all
individuals with moderate Alzheimer's disease[, redefined for Table 1
analysis as MMSE of 14 to 22, which includes two scores that Lovell
indicates show mild cognitive impairment, (i.e., 21 and 22)], regardless of
ApoE4 status, may benefit from high dose IVIG treatment." (Id. ,r 245.)
Thus, Appellants' Specification also belies that it was unexpected to find
that IVIG treats moderately severe AD who carry an APOE E4 allele. The
data just noted demonstrate a benefit regardless of APOE E4 status in
patients with an MMSE score between 14--22. And, that data demonstrate a
benefit to patients that would be considered by those of ordinary skill to
have mild AD.
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Furthermore, Appellants' argument that the reduction is significantly
reduced in the group with MMSE scores of 16-20 as compared to MMSE
scores 16-26 (Appeal Br. at 26) is not persuasive. A reduction is expected
in the narrow group of MMSE scores of 16-20 based on Relkin' s disclosure
and thus does not undercut the obviousness determination. Appellants'
argument seems to tum on the degree of the reduction, but superiority does
not undercut a reasonable expectation of success. See Hoffmann-La Roche
Inc. v. Apotex Inc., 748 F.3d 1326, 1333-34 (Fed. Cir. 2014) ("The evidence
of superior efficacy does nothing to undercut the showing that there was a
reasonable expectation of success with the 150 mg monthly dose, even if the
level of success may have turned out to be somewhat greater than would
have been expected.")
Moreover, "it is well settled that unexpected results must be
established by factual evidence." In re Geisler, 116 F.3d 1465, 1470 (Fed.
Cir. 1997). Appellants do not provide any factual evidence to establish the
difference observed in the reduced progression of AD in the group having
MMSE 16-20 as compared to MMSE 14--26 is a difference in kind rather
than merely a difference in degree. This is especially significant given that
Appellants' Specification also indicates "as shown in Table 1, analysis of the
data using redefined moderate disease cohorts, including subjects with
MMSE scores of 21 and 22, shows that subjects with moderate Alzheimer's
disease (e.g., MMSE of 14 to 22, inclusive) significantly benefit from high
dose IVIG treatment," and regardless of APOE E4 status. (Spec. ,r 245.)
Differences that only amount to a difference in degree do not establish
unexpected results. Bristol-Myers Squibb Co. v. Teva Pharms. USA, Inc.,
752 F.3d 967, 977 (Fed. Cir. 2014) (citing In re Papesch, 315 F.2d 381,392
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(CCPA 1963); In re Hoch, 428 F.2d 1341, 1344 n. 5 (CCPA 1970)); In re
Merck & Co., 800 F.2d 1091, 1099 (Fed. Cir. 1986) ("In the absence of
evidence to show that the properties of the compounds differed in such an
appreciable degree that the difference was really unexpected, we do not
think that the Board erred in its determination that appellant's evidence was
insufficient to rebut the prima facie case.").
While there is evidence in the Specification indicating that those with
MMSE of 21-26 or that were APOE E4 negative, when administered 400
mg/kg/2 week IVIG did not show slow down of progression of dementia as
measured by 3MS, compared to placebo (Figures 6 and7) (Appeal Br. 26-
28), Appellants' evidence and arguments do not establish that those who are
both APOE E4 positive and also have an MMSE score of 21-26 (data points
within Relkin' s teaching) did not have reduced progression. Indeed, it
would be surprising to see such data, in light of the Specification's teaching
that "[ o ]verall, treatment of Alzheimer's patients by administration of 400
mg/kg/2 week IVIG resulted in reduced progression," (Spec. ,r 231) and
where Relkin suggests reduction of progression would be expected in such a
group, just like those with MMSE of 14--20.
Finally, Appellants' evidence and arguments also do not establish an
unexpected result in patients within the claimed MMSE range of 14--22 or a
cohort that is MMSE 14--22 and APOE E4 positive. Nor does Appellants'
evidence demonstrate a significant difference over different measures, e.g.,
ADAS-Cog or CGIC. (See Spec. ,r,r 110-112, 239, Figure 32 (ADAS-Cog
mean and 95% confidence intervals), and Figure 33 (CGIC mean and 95%
confidence intervals).) It only demonstrated evidence with 95% confidence
intervals as to 3MS, but not for ADAS-Cog and CGIC, which are other
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Appeal2018-002497
Application 14/270, 192
assessments of cognitive measures in AD. (See, e.g., Spec. ,r,r 222, 238-239,
242.) "The evidence presented to rebut a primafacie case of obviousness
must be commensurate in scope with the claims to which it pertains." In re
Dill, 604 F.2d 1356, 1361 (CCPA 1979). We do not find the evidence
sufficiently commensurate in scope to rebut the prima facie case.
Claims 82, 83, 105, 111, 114, 115, 117-119, 121 and 122 have not
been argued separately and therefore fall with claim 79. 37 C.F.R.
§ 4I.37(c)(l)(iv).
Appellants argue claim 123 separately, but the arguments are directed
to why Relkin does not suggest treating a subset of patients that have both an
MMSE score of from 16-20 and who carry an APOE E4 allele. (Appeal Br.
38.) All of the reasons discussed above regarding why we do not find
Appellants' subset argument persuasive as to the Examiner's prima facie
case regarding patients with an MMSE score of from 14--22 and who carry
an APOE E4 allele apply equally to this slightly narrower subgroup.
Moreover, Appellants' evidence and arguments do not establish an
unexpected result in patients of this subgroup for the reasons discussed
regarding claim 79.
SUMMARY
We reverse the rejection claims 79, 105, 111, 114, 115, 117-119, and
121-123 under 35 U.S.C. § 102(a)(l) as anticipated by Relkin as evidenced
by Alz.org and Lovell.
We affirm the rejection of claims 79, 82, 83, 105, 111, 114, 115, 117-
119, and 121-123 under 35 U.S.C. § 103 as unpatentable over Relkin as
evidenced by Alz.org and Lovell.
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Appeal2018-002497
Application 14/270, 192
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
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