Jutta Amersdorffer et al.

Patent Trials and Appeals Board

Feb 4, 2020

14127217 - (D) (P.T.A.B. Feb. 4, 2020)

UNITED STATES PATENT AND TRADEMARK OFFICE
UNITED STATES DEPARTMENT OF COMMERCE
United States Patent and Trademark Office
Address: COMMISSIONER FOR PATENTS
P.O. Box 1450
Alexandria, Virginia 22313-1450
www.uspto.gov
APPLICATION NO. FILING DATE FIRST NAMED INVENTOR ATTORNEY DOCKET NO. CONFIRMATION NO.
14/127,217 12/18/2013 Jutta Amersdorffer MOR0006US.NP 9326
26259 7590 02/04/2020
LICATA & TYRRELL P.C.
66 E. MAIN STREET
MARLTON, NJ 08053
EXAMINER
DAHLE, CHUN WU
ART UNIT PAPER NUMBER
1644
NOTIFICATION DATE DELIVERY MODE
02/04/2020 ELECTRONIC
Please find below and/or attached an Office communication concerning this application or proceeding.
The time period for reply, if any, is set in the attached communication.
Notice of the Office communication was sent electronically on above-indicated "Notification Date" to the
following e-mail address(es):
PTOactions@licataandtyrrell.com
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
____________

BEFORE THE PATENT TRIAL AND APPEAL BOARD
____________

Ex parte JUTTA AMERSDORFFER, STEFAN STEIDL,
MARK WINDERLICH, SUSANNE KROHN, and LISA ROJKJAER
____________

Appeal 2018-008612
Application 14/127,217
Technology Center 1600
____________

Before ULRIKE W. JENKS, TIMOTHY G. MAJORS, and
MICHAEL A. VALEK Administrative Patent Judges.

JENKS, Administrative Patent Judge.

DECISION ON APPEAL
Pursuant to 35 U.S.C. § 134(a), Appellant1 appeals from Examiner’s
decision to reject the claims as obvious and provisionally on the ground of
nonstatutory obviousness-type double patenting. We have jurisdiction under
35 U.S.C. § 6(b).
We AFFIRM.

1 We use the word Appellant to refer to “applicant” as defined in 37 C.F.R.
§ 1.42(a). Appellant identifies the real party in interest as MorphoSys AG.
Appeal Br. 4.
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STATEMENT OF THE CASE
Claims 1, 4–6, and 9–12 are on appeal, and can be found in the
Claims Appendix of the Appeal Brief. Claim 1, reproduced below, is the
sole independent claim and is illustrative of the claimed subject matter:
1. A synergistic combination of an
(a) antibody specific for CD19 comprising an HCDRl
region of sequence SYVMH (SEQ ID NO:1), an HCDR2
region of sequence NPYNDG (SEQ ID NO: 2), an HCDR3
region of sequence GTYYYGTRVFDY (SEQ ID NO: 3), an
LCDRl region of sequence RSSKSLONVNGNTYLY (SEQ ID
NO: 4), an LCDR2 region of sequence RMSNLNS (SEQ ID
NO: 5), and an LCDR3 region of sequence MQHLEYPIT (SEQ
ID NO: 6) and wherein the heavy chain constant region
comprises amino acids 239D and 332E, wherein the Fc
numbering is according to the EU index as in Kabat and
(b) fludarabine for use in the treatment of non-Hodgkin’s
lymphoma, chronic lymphocytic leukemia and/or acute
lymphoblastic leukemia,
wherein said synergistic combination exhibits a
synergistic level with a combination index (CI) of less than or
equal to 0.3 in cell killing of MEC-1 leukemia cells, wherein
the CI is calculated according to the CI-isobol method of Chou-
Talalay.
Appeal Br. 21 (Claims Appendix).
REFERENCES
The prior art relied upon by Examiner is:
Name Reference Date
Bernett et al. (“Bernett”) US 8,524,867 B2 Sept. 3, 2013
Dreyling et al.
(“Dreyling”)
US 2011/0165152 Al July 7, 2011
Herting et al. (“Herting”) US 2011/0165151 Al July 7, 2011

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Horton et al., Potent In vitro and In vivo Activity of an Fc-Engineered
Anti-CD19 Monoclonal Antibody against lymphoma and leukemia, 68
Cancer Research 8049–56 (2008) (“Horton”)
Polito et al., The conjugate Rituximab/saporin-S6 completely inhibits
clonogenic growth of CD20-expressing cells and produces a synergistic
toxic effect with Fludarabine, 18 Leukemia 1215–22 (2004)
(“Bolognesi”)2
Weidmann et al., Bendamustine is effective in relapsed or refractory
aggressive non-Hodgkin’s lymphoma, 13 Annals of Oncology 1285–89
(2002) (“Weidmann”)
Woyach et al., A phase 1 trial of the Fc-engineered CD19 antibody
XmAb5574 (MOR00208) demonstrates safety and preliminary efficacy in
relapsed CLL, 124 Blood 3553–60 (2014) (“Woyach”)
REJECTIONS
The following grounds of rejection are before us for review:
I. Claims 1, 4–6, and 9–12 under 35 U.S.C. § 103(a) as unpatentable
over Horton, Bernett, Bolognesi, Dreyling, as evidenced by Woyach.
II. Claims 1, 4–6, and 9–12 provisionally on the ground of nonstatutory
obviousness-type double patenting over U.S. Application Serial
No. 14/126,928 in view of Weidman and Herting.

I. Obviousness
The issue is whether the preponderance of evidence of record supports
Examiner’s conclusion that one of ordinary skill in the art based on the
teaching of the references would have arrived at a combination therapy
composition containing an anti-CD19 antibody and fludarabine.

2 The first author’s name of this reference is Polito, because both Examiner
and Appellant refer to this reference as “Bolognesi” for consistency we will
do the same in this opinion. See Ans. 3; Appeal Br. 8.
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1. Findings of Fact
We agree with and adopt Examiner’s findings of fact and reasoning
regarding the scope and content of the prior art. For emphasis only, we
highlight the following:
FF1. Horton teaches that “CD19 is a 95-kDa transmembrane glycoprotein
of the immunoglobulin superfamily containing two extracellular
immunoglobulin-like domains and an extensive cytoplasmic tail.”
Horton 8049. Horton teaches that “CD19 is an attractive alternative
target for the immunotherapy of lymphoproliferative disorders, due to
its expression on a wide range of lymphomas and leukemias,
including some early B-cell malignancies that do not express CD20.”
Id. 8055.
FF2. Horton teaches “[a] humanized anti-CD19 antibody with an
engineered Fc domain (XmAb5574).” Horton Abstract.
FF3. Woyach teaches that CD19 antibody XmAb5574 (a.k.a. MOR00208)
is a humanized CD19 monoclonal antibody with an engineered Fc
region to enhance Fcγ receptor binding affinity. Woyach Abstract.
FF4. The Specification describes “MOR208” and “XmAb5574” as
synonymous and encompassed by the claims. Spec. 9. Additionally,
the Specification explains that “MOR208 is [fully] described in US
patent application No. 12/377,251” now issued as US 8,524,867 B2
(Bernett). Id
FF5. Bernett teaches methods of treating diseases of B-cell origin such as,
for example, “non-Hodgkin’s lymphoma (NHL), acute lymphoblastic
leukemia (ALL), and autoimmune related diseases” using the
modified anti-CD19 antibodies. See e.g., Bernett 12:27–36.
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FF6. Bernett teaches using the modified anti-CD19 antibodies in
conjunction with chemotherapeutic agents including purine analogs
such as fludarabine among others. Bernett 66:26.
FF7. Bolognesi teaches that “Fludarabine (FLU) is one of the most widely
used drugs for the treatment of indolent NHL” (Non-Hodgkin’s
lymphoma). Bolognesi 1218. In a cell-based assay FLU was able to
reduce cell growth by 80% but not eliminate it completely. Id. at
1219.
FF8. Dreyling teaches “Fludarabine is [(2R,3R,4S,5R)-5-(6-amino-2-
fluoro-purin-9-yl)-3,4-dihydroxy-oxolan-2-yl] methoxyphos-
phonicacid. It is DNA precursors/antimetabolites and functions as
halogenated ribonucleotide reductase inhibitor.” Dreyling ¶ 8.
Dreyling teaches administering fludarabine at a dosage 0.01 mg/kg to
about 30 mg/kg depending on the species, gender, age, and weight.
Id. ¶ 73; see also id. ¶ 132 (administering fludarabine at 40 mg/kg).
Dreyling teaches that “[t]he co-administration [of anti-CD20 antibody
and FLU] can be simultaneous or sequential in either order, wherein
preferably there is a time period while both (or all) active agents
simultaneously exert their biological activities.” Id. ¶ 70.

2. Analysis
We have reviewed Appellant’s contentions that Examiner erred in
rejecting claims 1, 4–6, and 9–12 as obvious over the cited art. Appeal
Br. 8–17; Reply Br. 2–4. We disagree with Appellant’s contentions, and
find that Examiner presented sufficient evidence to a support a conclusion of
obviousness.
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A. Claim interpretation
We begin with claim interpretation so we can properly compare the
scope of the claims to the prior art. “During examination, ‘claims . . . are to
be given their broadest reasonable interpretation consistent with the
specification, and . . . claim language should be read in light of the
specification as it would be interpreted by one of ordinary skill in the art.”‘
In re Am. Acad. of Sci. Tech. Ctr., 367 F.3d 1359, 1364 (Fed. Cir. 2004)
(quoting In re Bond, 910 F. 2d. 831, 833 (Fed. Cir. 1990)).
(i) Preamble: A synergistic combination of an
“If the preamble adds no limitations to those in the body of the claim,
the preamble is not itself a claim limitation and is irrelevant to proper
construction of the claim.” IMS Technology, Inc. v. Haas Automation, Inc.,
206 F.3d 1422, 1434 (Fed. Cir. 2000). The preamble in context with the
relevant portion of the body of claim 1 reads as follows:
1. A synergistic combination of an
. . .
wherein said synergistic combination exhibits a
synergistic level with a combination index (CI) of less than or
equal to 0.3 in cell killing of MEC-1 leukemia cells, wherein
the CI is calculated according to the CI-isobol method of Chou-
Talalay.
Appeal Br. 21 (Claims Appendix). Here, the preamble informs us that we
are considering a product. The question is does the preamble recitation of
“synergistic” by itself limit the claim structurally? See Catalina Mktg. Int’l,
Inc. v. Coolsavings.com, Inc., 289 F.3d 801, 809 (Fed. Cir. 2002). (“[T]he
patentability of apparatus or composition claims depends on the claimed
structure, not on the use or purpose of that structure.”). On this point, we do
not find evidence (see below I.2.A.iv) that the “synergistic” recitation in the
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preamble provides structural information with respect to the product. In
other words, the recitation of “synergistic” in the preamble does not limit
claim 1 beyond those structural requirements recited in the body of the
claim.
(ii) Claim body: antibody specific for CD19 comprising an
HCDRl region of sequence SYVMH (SEQ ID NO:1), an
HCDR2 region of sequence NPYNDG (SEQ ID NO: 2), an
HCDR3 region of sequence GTYYYGTRVFDY (SEQ ID NO: 3),
an LCDRl region of sequence RSSKSLONVNGNTYLY (SEQ ID
NO: 4), an LCDR2 region of sequence RMSNLNS (SEQ ID NO:
5), and an LCDR3 region of sequence MQHLEYPIT (SEQ ID
NO: 6) and wherein the heavy chain constant region comprises
amino acids 239D and 332E, wherein the Fc numbering is
according to the EU index as in Kabat
This element recites an antibody that recognizes a particular protein
structure and contains structural limitations pertaining to the antibody itself.
(iii) fludarabine for use in the treatment of non-Hodgkin’s
lymphoma, chronic lymphocytic leukemia and/or acute
lymphoblastic leukemia,
The element recites a chemotherapeutic agent.
Therefore, claim 1 is directed to a combination product containing
two active ingredients: (1) anti-CD19 antibody and (2) fludarabine.
(iv) wherein said synergistic combination exhibits a
synergistic level with a combination index (CI) of less than or
equal to 0.3 in cell killing of MEC-1 leukemia cells, wherein the
CI is calculated according to the CI-isobol method of Chou-
Talalay.
The wherein clause of the claim describes that the combination
exhibits a particular level of activity – a synergistic level– in a particular
assay system using a particular cell line while applying a particular statistical
analysis. The Specification provides that “synergistic” means “more than
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the expected additive effect of a combination.” Spec. 7. The claim,
however, does not recite a particular concentration level for each
component. In other words, the wherein clause describes a result achieved
by the combination product namely a particular level of activity for “the
treatment of non-Hodgkin’s lymphoma, chronic lymphocytic leukemia
and/or acute lymphoblastic leukemia” but does not recite the amount of each
component that achieves this result.
Thus, the dispute resolves on whether the “synergistic level”
limitation recited in the claim imparts a structural limitation on the
combination product itself or whether this limitation simply recites a
property that is necessarily present anytime the components are combined
and thereby inherent.
According to the Specification, all combinations of anti-CD19
antibody with fludarabine produce a synergistic level of response. For
example, the Specification recites the use of the combination product in an
in vitro a cell-killing assay using MEC-1 leukemia cells and applying the
recited statistical analysis. See Spec. 15–20 (Example 1). The Specification
provides two additional in vivo assays using the recited combination product
in a treatment application in mice. The first in vivo assay system uses a
“subcutaneously (SC)-implanted human Ramos Burkitt’s B-cell lymphoma
tumor growth model.” Id. at 19–22 (Example 2). The second in vivo model
injects Ramos human Burkitt’s lymphoma cells into the tail vain of a mouse
and measures survival. Id. at 22–25 (Example 3). The Specification,
therefore, establishes that a synergistic level of activity is achieved in three
different experimental settings, applying different concentrations of the
products, and applying different statistical analysis.
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Based on these disclosures in the Specification, we find that the
“synergistic level” limitation is not structural. This is because the
Specification does not provide evidence that shows that the “synergistic
level” response is achieved with some combinations, but not with others,
when the components are used within their known therapeutic range. A
showing that some combination of components produces a synergistic level
response, while other combinations do not, might support a conclusion that
recited effect is due to the particular manner in which the components are
combined together and, therefore, that claim is limited to that particular
structure. Because we find the recited “synergistic level” of activity in the
wherein clause of the claim does not impart any additional structural
requirement, we determine on this record that the recited “synergistic level”
is a property that is necessarily present anytime the two components are used
together.
B. Combining two components each known to treat lymphoma
such as non-Hodgkin’s lymphoma
We agree with and adopt Examiner’s rationale that it would have been
obvious to arrive at the combination product as claimed based on the
disclosed references because “both compounds (the anti-CD19 antibody
with S239D and I332E amino acid substitutions in the Fc region and
fludarabine) are known to be therapeutically effective in treating lymphomas
such as non-Hodgkin’s lymphoma.” Ans. 6, see id. at 7 (citing In re
Kerkhoven, 626 F.2d 846, 850 (CCPA 1980), MPEP 2144.06); see FF1–
FF3, FF5, FF6.
Appellant contends that Bernett’s teaching of coadministration of
anti-CD19 antibodies in conjunction with a chemotherapeutic agent selected
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from a list including at least 150 possible agents “is in no way predictive of
the synergistic combination” as claimed. Reply Br. 3; Appeal Br. 9.
We are not persuaded by Appellant’s contention that Bernett does not
suggest the combination product as recited in the claims. Bernett teaches the
use of the anti-CD19 antibody, the same antibody as recited in the instant
claims (see FF4–FF6), and instructs that the antibody be administered in
conjunction with a chemotherapeutic agent such as fludarabine (FF6).
“Disclos[ing] a multitude of effective combinations does not render any
particular formulation less obvious. This is especially true because the
claimed composition is used for the identical purpose taught by the prior
art.” Merck & Co. v. Biocraft Laboratories Inc., 874 F.2d 804, 807 (Fed.
Cir. 1989). Thus, Appellant’s argument that fludarabine is one of numerous
potential chemotherapeutics is unavailing.
C. Inherency
Appellant contends that obviousness cannot be predicated on what is
not known at the time of the invention. Appeal Br. 14 (citing In re
Rijckaert, 9 F.3d 1531, 1534 (Fed. Cir. 1993); MPEP 2141.02). It is
Appellant’s position that unless the prior art has done the experiments there
is no way to predict that the composition has the recited effect on cell killing
based on the CI-Isobel analysis. We are not persuaded by Appellant’s
contention. The anti-CD19 antibody and fludarabine composition “cannot
become nonobvious simply by . . . claiming the [synergistic level property]
. . . . To hold otherwise would allow any formulation—no matter how
obvious—to become patentable merely by testing and claiming an inherent
property.” Santarus, Inc. v. Par Pharm., Inc., 694 F.3d 1344, 1354 (Fed.
Cir. 2012).
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The prior art cited by Examiner provides a reasonable expectation of
success that the coadministration of anti-CD19 antibody and fludarabine
results in the reduction of diseases of B-cell origin such as non-Hodgkin’s
lymphoma (NHL), acute lymphoblastic leukemia (ALL), and autoimmune
related diseases. FF1–FF6; see In re O’Farrell, 853 F.3d 894, 903–04 (Fed.
Cir. 1988) (“Obviousness does not require absolute predictability of success
. . . all that is required is a reasonable expectation of success.”). Our
reviewing court has held that when the prior art does not expressly disclose a
claim limitation, inherency may supply the missing element. See Persion
Pharm. LLC v. Alvogen Malta Operations Ltd., Case No. 18-2361 (Fed. Cir.
Dec. 27, 2019) and Hospira, Inc. v. Fresenius Kabi USA, LLC., Case No.
19-1329, 19-1367 (Fed. Cir. Jan. 9, 2020). “Inherency is established in the
context of obviousness when ‘the limitation at issue necessarily must be
present, or the natural result of the combination of elements explicitly
disclosed by the prior art.’” Hospira, slip op. at 10 (Fed. Cir. Jan. 9, 2020)
(citing Par Pharm. v. TWI Pharm., Inc., 773 F.3d 1186, 1195–96 (Fed. Cir.
2014)). Here, we agree with Examiner’s finding that the function recited in
the wherein clause flows naturally from the teachings of the prior art.
Ans. 16 (citing Ex parte Obiaya, 227 USPQ 58, 60 (Bd. Pat. App. & Inter.
1985 (“The fact that appellant has recognized another advantage which
would flow naturally from following the suggestion of the prior art cannot
be the basis for patentability when the differences would otherwise be
obvious.”), and Atlas Powder Co. v. Ireco Inc., 190 F.3d 1342, 1347 (Fed.
Cir. 1999) (“[T]he discovery of . . . a scientific explanation for the prior art’s
functioning, does not render the old composition patentably new to the
discoverer.”)).
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As discussed above, the Specification does not provide any indication
from which to conclude that the “synergistic level” limitation as recited in
the wherein clause of claim 1 imparts a structural limitation onto the claimed
combination. We, therefore, agree with Examiner that based on at least the
teaching of Bernett that it would have been reasonable to conclude that the
combination anti-CD19 antibody and fludarabine would be effective for the
purpose of treating diseases of B-cell origin such as non-Hodgkin’s
lymphoma (NHL), acute lymphoblastic leukemia (ALL), and autoimmune
related diseases. FF5–FF6; see Ans. 3–8. An obvious formulation cannot
become nonobvious simply by measuring and claiming an activity of the
formulation in a particular context, “because ‘[t]o hold otherwise would
allow any formulation—no matter how obvious—to become patentable
merely by testing and claiming an inherent property.’” Persion Pharm., slip
op. at 13 (Fed. Cir. Dec. 27, 2019) (citing Santarus, Inc. v. Par Pharm., Inc.,
694 F.3d 1344, 1354 (Fed. Cir. 2012)); see also Gen. Elec. Co. v. Jewel
Incandescent Lamp Co., 326 U.S. 242, 249 (1945) (“It is not invention to
perceive that the product which others had discovered had qualities they
failed to detect.”).
D. Unexpected results
Although, as discussed above, we interpret that the wherein clause
does not provide any structural limitation on the combination product, the
limitation is still part of the claim and can reasonably be interpreted to
encompass an allegedly unexpected property of the claimed combination.
We have reviewed Appellant’s unexpected result arguments (see Appeal Br.
16), but do not find them persuasive. As Examiner explains, secondary
considerations, when present, must be taken into account but do not control
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the obviousness conclusion. See Ans. 16. “[W]e attribute no magic status to
synergism per se since it may be expected or unexpected.” In re
Huellmantel, 324 F.2d 998, 1003 (CCPA 1963).
As explained above, Bernett and Horton teaches all of the elements of
claim 1 and provide an express motivation to combine those teachings as
articulated in Examiner’s rejection for the treatment of diseases such as non-
Hodgkin’s lymphoma. See Ans. 6 (“One of ordinary skill in the art would
have been motivated to do so, and have a reasonable expectation of success,
because both compounds (the anti-CD19 antibody with S239D and I332E
amino acid substitutions in the Fc region and fludarabine) are known to be
therapeutic[ally] effective in treating lymphomas such as non-Hodgkin’s
lymphoma.”); FF1–FF3, FF5, FF6. Weighing that evidence together with
Appellant’s evidence of a purportedly unexpected result as incorporated into
the claim, which on balance is weak, we determine that the preponderance of
the evidence supports Examiner’s obviousness rejection. See, e.g., Bayer
Pharma AG v. Watson Labs., Inc., 874 F.3d 1316, 1329 (Fed. Cir. 2017)
(weighing evidence of unexpected results and copying together with other
evidence, including “strong evidence of a motivation to make the claimed
combination” in the cited prior art, to conclude that combination was
obvious); Bayer Healthcare Pharm., Inc. v. Watson Pharm., Inc., 713 F.3d
1369, 1377 (Fed. Cir. 2013) (finding that secondary indicia evidence did not
“overcome[] the plain disclosures and express motivation to combine those
disclosures in the prior art”).
E. Summary
For the reasons discussed, we are not persuaded that Examiner failed
to make out a prima facie case of obviousness. We are also not persuaded
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that the evidence advanced by Appellant to show an unexpected result
outweighs the evidence supporting a conclusion of obviousness.
Accordingly, we affirm the rejection of claim 1.
F. Alternative argument based on substitution of antibodies
Lastly, Examiner presents an alternative theory that “the substitution
of the known afucosylated anti-CD20 antibody for the Fc modified anti-
CD19 antibody XmAb5574 would have yielded predictable result of
synergistic effect in killing lymphoma cells.” Ans. 7.
Appellant contends that Examiner’s reliance on the “common
mechanism of action based upon enhanced ADCC function alone” is
misplaced because it does not take into account “that fludarabine upregulates
the expression of CD20, not CD19.” Reply Br. 3–4; see Steidl Dec. ¶¶ 4, 9;3
Appeal Br. 11. “[T]he number of target molecules on the cell surface has an
influence on the cytotoxicity of ADCC inducing antibodies.” Steidl Dec. ¶ 4;
see Appeal Br. 11. “ADCC-mediating antibodies require stable cell surface
expression of the target antigen to enable Fc-receptor engagement by ADCC
effector cells like NK cells.” Appeal Br. 13 (citing Steidl Dec. ¶ 8).
Examiner responds that the claimed Fc engineered anti-CD19
antibody (with enhanced ADCC effect) was known. See Ans. 7, 13; FF1–
FF3, FF5, FF6. Examiner concludes that based on the teachings in the art “it
would have been obvious to one of ordinary skill in the art to replace the
anti-CD20 antibody [disclosed in Dreyling] in the synergistic combination
with fludarabine” with the anti-CD19 antibody disclosed in Horton or
Bernett. Non-Final Act. 7. As discussed above (see I.2.B–I.2.E), we agree

3 Declaration under 37 C.F.R. § 1.132 by Stefan Steidl signed April 12, 2017
(“Steidl Dec.”).
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with Examiner that there is clear teaching in Bernett to combine the anti-
CD19 and fludarabine for the purpose of treating non-Hodgkin’s lymphoma
arriving at a reasonable expectation of success.
We do not, however, agree with Examiner’s position that just because
CD19 and CD20 are both cell surface molecules expressed on B-cells is
sufficient commonality to say they are functional equivalents. See Ans. 14–
15; see Steidl Dec. ¶¶ 4, 9; see Appeal Br. 10–11. “CD19 is a 95-kDa
transmembrane glycoprotein of the immunoglobulin superfamily containing
two extracellular immunoglobulin-like domains and an extensive
cytoplasmic tail.” FF1. CD19 “is B-lineage-specific and functions as a
positive regulator of B-cell receptor signaling in conjunction with CD21 and
CD81.” Horton, 8049. On the other hand, “[t]he CD20 antigen, [is] a 33- to
37-kDa membrane protein of unknown function, is an excellent
immunotherapy target as it is expressed only on mature B cells and not on
B-cell precursors.” Bolognesi 1215. Here, the record supports Appellant’s
position that CD19 and CD20 are different molecules with different, yet
overlapping, cellular expression patterns. Because of these different
structural and cellular expression patterns we do not agree with Examiner’s
alternative theory, which is based on a simple substitution of anti-CD20
antibody in Bolognesi or Dreyling for anti-CD19 taught in Horton or Bernett
to arrive at the claimed combination product.
3. Conclusion
We conclude, considering the totality of the cited evidence and
arguments, that the preponderance of the evidence supports Examiner’s
conclusion of obviousness with respect to claim 1 (see above I.2.B–I.2.E),
and Appellant has not provided sufficient rebuttal evidence or evidence of
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secondary considerations that outweighs the evidence supporting Examiner’s
conclusion. As Appellant does not argue the claims separately, claims 4–6
and 9–12 fall with claim 1. 37 C.F.R. § 41.37 (c)(1)(iv).

II. Provisional Nonstatutory Obviousness-Type Double Patenting
The issue is whether the preponderance of evidence of record supports
Examiner’s conclusion that claims of the copending U.S. Application No.
14/126,928 are not patentably distinct.
1. Findings of Fact
FF9. Claim 1 of co-pending U.S. Application No. 14/126,928 reads as
follows:
Claim 1 A synergistic combination of an
antibody specific for CD19 comprising an HCDRl region
of sequence SYVMH (SEQ ID NO: 1), an HCDR2 region of
sequence NPYNDG (SEQ ID NO: 2), an HCDR3 region of
sequence GTYYYGTRVFDY (SEQ ID NO: 3), an LCDRl
region of sequence RSSKSLONVNGNTYL Y (SEQ ID NO:
4), an LCDR2 region of sequence RMSNLNS (SEQ ID NO: 5),
and an LCDR3 region of sequence MQHLEYPIT (SEQ ID NO:
6) and wherein a constant region comprises amino acids 239D
and 332E, wherein the Fc numbering is according to the EU
index as in Kabat and
bendamustine for use in the treatment of non-Hodgkin’s
lymphoma, chronic lymphocytic leukemia and/or acute
lymphoblastic leukemia
wherein said synergistic combination exhibits a
synergistic level of cell killing in a chronic B-cell leukemia cell
line in comparison to antibody or bendamustine alone and a
combination index (CI) of less than 0.75 in cell killing of MEC-
1 leukemia cells, wherein the CI is calculated according to the
CI-isobol method of Chou-Talalay.
U.S. Application No. 14/126,928 (Amendment of November 7, 2017.)
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FF10. Weidmann teaches “bendamustine as a single agent in aggressive non-
Hodgkin’s lymphoma.” Weidmann 1285.
FF11. Herting teaches that “[b]endamustine is a nitrogen mustard used in the
treatment of chronic lymphocytic leukemia (CLL) . . . non-Hodgkin’s
lymphoma (NHL).” Herting ¶ 34. Bendamustine “belongs to the
family of drugs called alkylating agents.” Id.
2. Analysis
According to Examiner, “the conflicting claims are not identical, they
are not patentably distinct from each other because like the instantly recited
fludarabine, bendamustine is known to be an effective agent for lymphoma
therapy.” Ans. 9.
Appellant contends that the CD19 antibody “is used in combination
with a completely different therapeutic agent than claimed, specifically
bendamustine versus fludarabine.” Appeal Br. 18. Furthermore, Appellant
contends that “fludarabine and bendamustine are different chemotherapeutic
agents with different chemical structures.” Reply Br. 5. Fludarabine is a
purine analog (see FF6) while bendamustine is an alkylating agent (see
FF11). Although Examiner identified that these two compounds are used for
treating lymphomas, they do not share a common mechanism of action, nor
has Examiner demonstrated that one of skill in the art would consider them
to be within the same class of chemotherapeutic agents. Therefore, we agree
with Appellant that Examiner has not provided a sufficient rationale to
establish that fludarabine and bendamustine are functional equivalents, such
that it would have been obvious to replace one for the other, to support the
conclusion that the present claims and those in copending U.S. Application
No. 14/126,928 are not patentably distinct.
Appeal 2018-008612
Application 14/127,217

18
3. Conclusion
We conclude that the evidence cited by Examiner does not support a
conclusion that the copending claims renders the present claims obvious.
Accordingly, we reverse the provisional nonstatutory obviousness-type
double patenting rejection.

DECISION SUMMARY
In summary:
Claims
Rejected
35 U.S.C. § Reference(s)/Basis Affirmed Reversed
1, 4–6, 9–12 103 Horton, Bernettm
Bolognesi,
Dreyling, Woyach
1, 4–6, 9–
12

1, 4–6, 9–12 Provisional
nonstatutory
obviousness-type
double patenting
1, 4–6, 9–
12
Overall
Outcome
1, 4–6, 9–
12

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). See 37 C.F.R.
§ 1.136(a)(1)(iv).

AFFIRMED