Ex Parte Goldenberg et al

Patent Trial and Appeal Board

Oct 5, 2017

13617059 (P.T.A.B. Oct. 5, 2017)

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.
13/617,059 09/14/2012 David M. Goldenberg IMMU-0022US2A 1011
37013 7590 10/10/2017
Rossi, Kimms & McDowell LLP
20609 Gordon Park Square
Suite 150
Ashburn, VA 20147
EXAMINER
SCHWADRON, RONALD B
ART UNIT PAPER NUMBER
1644
NOTIFICATION DATE DELIVERY MODE
10/10/2017 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):
mail@rkmllp.com
EOfficeAction@rkmllp.com
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
BEFORE THE PATENT TRIAL AND APPEAL BOARD
Ex parte DAVID M. GOLDENBERG, CHIEN-HSING CHANG, and
HANS J. HANSEN
Appeal 2017-002095
Application 13/617,0591
Technology Center 1600
Before JOHN G. NEW, ELIZABETH A. LaVIER, and DAVID COTTA,
Administrative Patent Judges.
LaVIER, Administrative Patent Judge.
DECISION ON APPEAL
Pursuant to 35 U.S.C. § 134(a), Appellants seek review of the
Examiner’s rejections of claims 1,2, 4—14, 16—19, 21—25, and 28. We have
jurisdiction under 35 U.S.C. § 6(b). For the reasons of record and those set
forth below, we AFFIRM.
BACKGROUND
The Specification relates to “structural variants of anti-CD20
antibodies and/or antigen binding fragments thereof, preferably involving
1 Appellants state the real party in interest is Immunomedics, Inc. Appeal Br.
2.
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the amino acid sequences of complementarity-determining regions (CDRs),
with improved therapeutic characteristics.” Spec. 12. Claim 1 is
illustrative:
1. A method of treating a disease in a subject comprising:
a) obtaining a bispecific antibody or antibody fusion protein
comprising
(i) a first antibody or fragment thereof which binds to
human CD20 and which is a substituted chimeric,
humanized or human anti-CD20 antibody or antigen
binding fragment thereof made by a method comprising
making one amino acid substitution in the third
complementarity determining region (CDR) sequence of
the heavy chain of a chimeric, humanized or human anti-
CD20 antibody or antigen binding fragment thereof to
make a substituted antibody or antigen binding fragment
thereof, wherein the antibody is substituted at Rabat
position 101 of CDR3 and the substituted antibody or
antigen binding fragment thereof has at least one
improved characteristic selected from the group
consisting of a slower off-rate, slower antigen
dissociation rate, higher CDC activity, higher ADCC
activity, higher apoptotic activity, greater ability to
induce cell death in vitro in the absence of cross-linking
and greater ability to kill or inhibit the growth of CD20-
positive cells in vivo when administered to a subject with
CD20-positive cells and
(ii) a second antibody or fragment thereof:
b) administering the bispecific antibody or antibody fusion
protein to a subject; and
c) treating the disease in the subject, wherein the disease is
selected from the group consisting of B-cell mediated immune
disease, autoimmune disease, B-cell lymphoma and leukemia,
graft-versus-host disease, organ transplant rejection, immune
hemolytic anemia, allosensitization, and cryoglobulinemia.
Appeal Br. 18 (Claims Appendix) (some formatting added).
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REJECTIONS MAINTAINED ON APPEAL
1. Claims 1, 2, 4—14, 16—19, 21—25, and 28 stand rejected under
the judicially-created doctrine of nonstatutory double patenting as
unpatentable over claims 1—15 of the ’864 patent.2 Ans. 2.
2. Claims 1, 2, 4—12, 14, 16—18, 21—25, and 28 stand rejected
under 35 U.S.C. § 112(a) as failing to comply with the written
description requirement. Ans. 2.
3. Claims 1, 2, 4, 12, 14, 16—19, 21, and 28 stand rejected under
35 U.S.C. § 102(b) as anticipated by Hansen ’433.3 Ans. 5.
4. Claims 1, 2, 4—12, 14, 16—18, and 21—25 stand rejected under
35 U.S.C. § 102(b) as anticipated by Smith.4 Ans. 6.
5. Claims 1, 2, 4, 12—14, 16—19, and 21 stand rejected under 35
U.S.C. § 103(a) as unpatentable over Hansen ’433. Ans. 6.
DISCUSSION
As explained herein and for the reasons of record, we affirm the
Examiner’s rejections, except that as to Rejection 2 (written description), we
reverse the rejection of claim 28.
A. Rejection 1: Obviousness-type Double Patenting
Claim 1 of the ’864 patent generally recites a method of treating
disease using an “anti-CD20 antibody or antigen binding fragment thereof,”
2 Goldenberg et al., US 8,287,864 B2, issued Oct. 16, 2012.
3 Hansen et al., US 2003/0219433 Al, published Nov. 27, 2003.
4 Smith et al., US 2008/0089885 Al, published Apr. 17, 2008.
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with the same substitution as the present claims, i.e., at “Kabat position 101
of CDR3.” Appellants argue, without further analysis, that tc[b]ispecific
antibodies and antibody fusion proteins are patentably distinct from
antibodies and fragments thereof.” Appeal Br. 14. Without more, this
assertion is not persuasive. Nor is it fully responsive to the Examiner’s
position. As the Examiner points out, claim 10 of the ’864 patent depends
on claim 1, and recites that the antibody can be conjugated to at least one
therapeutic agent; claim 11 further recites that the agent can be an antibody.
Final Action 3. Accordingly, we agree with the Examiner’s finding that
“both sets of claims encompass the use of bispecific antibody fusion proteins
(including fusion proteins containing an interferon) to treat the diseases
recited” {id.), and thus are not patentably distinct.
Therefore, we affirm the rejection of claims 1, 2, 4—14, 16—19, 21—25,
and 28 on the ground of nonstatutory double patenting as unpatentable over
claims 1—15 of the ’864 patent.
B. Rejection 2: Written Description5
The test for written description “requires an objective inquiry into the
four comers of the specification from the perspective of a person of ordinary
5 Appellants also argue we should reverse this rejection because the parent
application issued (as the ’864 patent) “with claims in which the anti-CD20
antibody was defined with the same language as in in the present case.”
Appeal Br. 14. Appellants note that the examiner of the parent application
“never questioned” the adequacy of the written description in that case (Reply
6), and so neither should we. This procedural argument is not persuasive.
“[Ejxaminers are not bound to follow other examiners’ interpretations,”
Dayco Products Inc. v. Total Containment Inc., 329 F.3d 1358, 1368 (Fed.
Cir. 2003), and neither are we. Nonetheless, “knowledge of a potentially
different interpretation is clearly information that an examiner could consider
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skill in the art. Based on that inquiry, the specification must describe an
invention understandable to that skilled artisan and show that the inventor
actually invented the invention claimed.” Ariad Pharms., Inc. v. Eli Lilly &
Co., 598 F.3d 1336, 1351 (Fed. Cir. 2010) (enbanc). Although it is possible
for a single species to adequately support a genus, see MPEP § 2163
(II)(A)(3)(a)(ii) (collecting cases), “a patentee of a biotechnological
invention cannot necessarily claim a genus after only describing a limited
number of species because there may be unpredictability in the results
obtained from species other than those specifically enumerated,” Noelle v.
Lederman, 355 F.3d 1343, 1350 (Fed. Cir. 2004).
1. Claim 1
The Examiner finds that although the rejected claims “encompass a
mutant antibody with the particular functional attributes recited[,] ... the
specification only describes a single example of such an antibody with a
single defined mutation.” Final Action 4. The Examiner finds this single
example to be inadequate to support the scope of claim 1, because “[t]he
identity of other antiCD20 antibodies with differing CDR regions that
contain the claimed mutation or different amino acid substitutions that have
the functional properties recited in the claims is unknown and
unpredictable.” Id.
Appellants argue that the Specification describes not one example, but
several. See Appeal Br. 14—15 (citing Spec. 1148, Examples 1, 2, & 25).
important.” Id. We do not ignore that the examiner in the related case did not
reject similar claims for inadequate written description. However, this non­
rejection does not persuade us that the Examiner in the present application
erred in rejecting claims 1, 2, 4—12, 14, 16—18, and 21—25 as inadequately
described, for the reasons described herein.
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According to Appellants, the results of the studies described in the
Specification “surprisingly determined that especially substitution at position
101 was of major importance” in the antibody’s improved characteristics as
recited in the claims. Id. at 15. As the Examiner points out, however, the
variants described in the cited Examples either have aspartate (e.g.,
veltuzumab) or asparagine (e.g., D101N) at position 101 in the heavy chain
of CDR3. See Ans. 11; Spec. Table 1. Further, the Examiner finds that “the
D101N substitution represents the original residue found in Rituximab
wherein said antibody does not have the properties recited in claim 1 (aka
see Example 25 wherein said antibody has a faster off-rate, not slower off-
rate).” Ans. 11. As asparagine is the original residue at Rabat position 101,
it is not a “substitution] at Rabat position 101 of CDR3” as required by
claim 1.
Here, supported by a review of the state of the relevant art, the
Examiner finds that “[t]he identity of other antiCD20 antibodies with
differing CDR regions that contain the claimed mutation or different amino
acid substitutions that have the functional properties recited in the claims is
unknown and unpredictable.” Final Action 5. Because the Specification
provides data for only one substitution at position 101, it is unclear whether
the claimed improved characteristics are the result of the aspartate
substitution in particular, or of substitution at this position generally. As
claim 1 does not identify or limit the substitution at position 101, we agree
with the Examiner that the Specification does not adequately describe the
claimed genus. Accordingly, we affirm the rejection of claim 1 for lacking
sufficient written description. Claims 2, 4—12, 14, 16—18, and 21—25, which
are not argued separately, fall with claim 1.
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2. Claim 28
Appellants argue separately claim 28, which depends from claim 1,
and further recites “replacing the asparagine residue at Kabat position 101 of
the heavy chain CDR3 of the antibody with an aspartate residue.” Appeal
Br. 21 (Claims Appendix). This is the very substitution exemplified in the
Specification, i.e., the one that is “made when producing veltuzumab.” Id. at
15. Appellants suggest that claim 28 was improperly included in the ground
of rejection because claims 13 and 19, which recite veltuzumab, were not
rejected under this ground. Id. at 15—16. We agree. We reverse this
rejection of claim 28.6
C. Rejection 3: Anticipation (Hansen ’433)
The Examiner finds, with respect to claim 1, that Hansen ’433 teaches
the use of veltuzumab “in a bispecific antibody with multiple copies of the
same or another antiCD20 antibody for the treatment of multiple sclerosis.”
Final Action 6 (citing Hansen ’433 Tflf 85, 162, 108, 184, 185, claims 11—17).
6 Our reversal of the written description rejection of claim 28 renders moot
Appellants’ argument in the Reply Brief that if the Specification does not
show possession of the claimed invention, neither can Hansen ’433 (which
shares some inventors with the present application), because Hansen ’433’s
“priority is the same as the earliest priority of the present invention.” Reply
Br. 5. There is a “subtle distinction between a written description adequate
to supports claim under § 112 and a written description sufficient
to anticipate its subject matter under § 102(b).” Vas-Cath Inc. v. Mahurkar,
935 F.2d 1555, 1562 (Fed. Cir. 1991). To wit, “the description of a single
embodiment of broadly claimed subject matter constitutes a description of the
invention for anticipation purposes” even if “the same information in a
specification might not alone be enough to provide a description of that
invention for purposes of adequate disclosure.” Id. (quoting In reLukach, 442
F.2d 967, 970 (CCPA 1971)).
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The Examiner finds that veltuzumab “inherently has the functional attributes
recited in the claims because it is the antibody recited in claim 1.” Id. at 7.
Appellants begin by noting that the rejected claims are drawn to a
method, not a product or composition (see Appeal Br. 3—5), and rely on this
distinction to argue that:
A method as recited in claim 1 is not disclosed in Hansen ’433.
Therefore, the subject matter of claim 1 is novel over Hansen
’433. It does not matter whether a possible product of such
method, namely veltuzumab, is already known in the art. The
mere existence of a product which can be obtained by the
claimed method does not disclose or suggest such method claim
if the method as such is novel and based on an inventive step.
Id. at 7; see also Reply Br. 1—2.
Appellants are correct that a known product can be the subject of a
patentable method claim. However, as the Examiner points out (see Ans.
13), the inherency doctrine applies to method claims as well as product
claims. In affirming a district court’s judgment that a method claim was
invalid, the Federal Circuit explained inherency thusly:
a prior art reference may anticipate when the claim limitation or
limitations not expressly found in that reference are nonetheless
inherent in it. See In re Oelrich, 666 F.2d [578, 581 (CCPA
1981)]; Verdegaal Bros., Inc. v. Union Oil Co. of Cal., 814 F.2d
628, 630, 2 USPQ2d 1051, 1053 (Fed. Cir. 1987). Under the
principles of inherency, if the prior art necessarily functions in
accordance with, or includes, the claimed limitations, it
anticipates. See In re King, 801 F.2d 1324, 1326, 231 USPQ
136, 138 (Fed. Cir. 1986). Inherency is not necessarily
coterminous with the knowledge of those of ordinary skill in
the art. Artisans of ordinary skill may not recognize the
inherent characteristics or functioning of the prior art. See id.,
801 F.2d at 1326.
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MEHL/Biophile Int’l Corp. v. Milgraum, 192 F.3d 1362, 1365 (Fed. Cir.
1999).
Here, the Examiner finds that Hansen ’433 teaches the use of a
substituted antibody within the scope of claim 1 (i.e., veltuzumab) to treat a
disease within the scope of claim 1 (i.e., multiple sclerosis, an autoimmune
disorder). The “at least one improved characteristic” recited in claim 1
would have flowed necessarily from the claimed substitution; it is
immaterial whether one of ordinary skill in the art at the time of the
invention would have recognized the improvement. Appellants’ assertion
that Hansen ’433 lacks a “suggestion or reasonable expectation” that the
substitution would result in the claimed functional changes (Appeal Br. 6) is
not germane to a § 102 rejection.
Having considered Appellants’ arguments, we are unpersuaded that
the Examiner erred in rejecting claim 1 as anticipated by Hansen ’433.
Claims 2, 4, 12, 14, 16—19, 21, and 28, which are not argued separately, fall
with claim 1.
D. Rejection 4: Anticipation (Smith)
With respect to exemplary claim 1, the Examiner finds:
Smith et al. teach a CDR3 substituted anti CD20 antibody
recited in the claims (see [0123] wherein the substituted Asn in
CDR3 is at position 101 of said antibody (aka the same position
in CDR3)). The antibody has the properties recited in the
claims (see [0106]) and would therefore have the various
functional attributes recited in the claims. Smith et al. teach use
of said antibody to treat multiple sclerosis at a dosage
encompassed by those recited in the claims (see [0286],[0269]).
Smith et al. teach sc administration of said antibody (see
[0273]). The antibody can be bispecific and contain antibodies
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which bind different epitopes on CD20 (see
[0064],[0080],[0081]).
Final Action 7—8.7
Appellants compare SEQ ID NO:4 of Smith with the amino acid
sequence for veltuzumab. See Appeal Br. 10. According to Appellants, the
number and nature of the differences between SEQ ID NO:4 and veltuzumab
mean that Smith does not anticipate because (1) there are too many
differences (Smith 1124 discloses sequences with “at least 85% sequence
identity” with SEQ ID NO:4) and (2) bridging the differences would require
non-conservative substitutions (contrary to the conservative amino acid
substitutions discussed in Smith 1124). See id. at 9-12; see also Reply Br.
3-5.
The Examiner responds that the claims subject to Rejection 4 do not
specifically recite veltuzumab, rendering Appellants’ veltuzumab-specific
arguments beside the point, and further notes that the claims do not “define
the nature of the substituted amino acid.” Ans. 16. We agree. As the
Examiner further explains, “section [0124] states ‘at least 85% sequence
identity’ wherein the sequence minimally has one of the substitutions recited
in section [0124], A single substitution in the sequence would result in a
sequence that has ‘at least 85% sequence identity’.” Id. (emphasis omitted).
We are not persuaded by Appellants’ arguments and we consequently
affirm the Examiner’s rejection of claim 1 as anticipated by Smith. Claims
2, 4—12, 14, 16—18, and 21—25, which are not argued separately, fall with
claim 1.
7 The Examiner also notes that “the disclosure of [0123] continues on to the
next paragraph wherein the substitution recited in the claims is disclosed.”
Final Action 8. Paragraph 124 of Smith discusses SEQ ID NON.
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E. Rejection 5: Obviousness (Hansen ’433)
1. Claims 1, 2, 4, 12, 14, 16—19, and 21
For claims 1,2, 4, 12, 14, 16—19, and 21, Appellants argue solely by
reference to their arguments presented for the § 102 rejection over Hansen
’433. See Appeal Br. 13. We have already dispensed with these arguments
in the context of Rejection 3, as discussed above. Accordingly, we need not
recite the particulars of the § 103 rejection generally, except to state that we
adopt the Examiner’s findings and analysis as set forth on pages 8—9 of the
Final Action and as further explained in pages 12—13 of the Answer.
However, within Appellants’ discussion of the § 102 rejection, we
discern one argument relevant primarily to the § 103 rejection (though
Appellants do not flag it as such or expressly reiterate it in discussing
Rejection 5). Specifically, Appellants assert that Hansen ’433 “provides no
suggestion or reasonable expectation” to the skilled artisan that the residue
substitution at position 101 “would result in the functional changes recited in
the claimed method.” Appeal Br. 6. Although inherency is more
circumscribed in the context of obviousness than anticipation, a disclosure is
inherent for obviousness purposes if it is “sufficient to show that the natural
result flowing from the operation as taught would result in the performance
of the questioned function.” PAR Pharm., Inc. v. TWI Pharms., Inc., 773
F. 3d 1186, 1195 (Fed. Cir. 2014) (quoting In re Oelrich, 666 F.2d 578, 581
(CCPA 1981)). As discussed above, here the “at least one improved
characteristic” recited in claim 1 would have flowed necessarily from the use
of veltuzumab to treat multiple sclerosis described in Hansen ’433, whether
the ordinarily skilled artisan would have appreciated it or not.
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Accordingly, we affirm the Examiner’s § 103 rejection of claim 1.
Claims 2, 4, 12, 14, 16—19, and 21, which are not argued separately, fall with
claim 1.
2. Claim 13
Claim 13 depends from claim 1, and further recites “wherein the first
antibody is veltuzumab and administration is to a subject who is refractory
to rituximab.” Appeal Br. 20 (Claims Appendix). The Examiner finds that
claim 13 would have been obvious over Hansen ’433 in light of its teaching
of rituximab as a conventional, but inadequate, therapy, and its further
teaching of the effectiveness of veltuzumab in treating a cancer for which
chemotherapy had failed. See Final Action 9 (citing Hansen ’433 1 8,
Example 5).
Appellants argue that, at the time Hansen ’433 was filed (in 2002),
rituximab was not a conventional therapy, as it was not approved for treating
any autoimmune disease until 2006, and Phase 2 trials were only begun in
2014. Appeal Br. 13. This argument is not persuasive both because it is
unsupported by evidence and because it misses the point.8 As cited by the
8 To the extent that Appellants imply that a therapy must achieve regulatory
approval before serving as a motivation for further improvement in the field,
we reject this argument. Appellants offer no legal authority in support of such
a proposition, which would leave the ordinarily skilled artisan unaware of, or
at least uninspired by, early-stage advances in their field. To the contrary, an
obviousness analysis “need not seek out precise teachings directed to the
specific subject matter of the challenged claim,” as a tribunal “can take
account of the inferences and creative steps that a person of ordinary skill in
the art would employ.” KSR Int’l Co. v. Teleflex Inc., 550 U.S. 398, 418
(2007).
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Examiner (see Final Action 9), rituximab9 is described as a prior art
antibody that “has activity against B-cell lymphomas,” but that does not
have a high response rate that is for patients with the more prevalent, lethal
forms (Hansen ’433 1 8). Accordingly, “a need exists to develop an
immunotherapy for B-cell malignancies that achieves a therapeutic response
of significant duration.” Id.
As further evidence that rituximab was known in the prior art as a
treatment for autoimmune disease, the Examiner refers to Curd,10 previously
of record in this prosecution. See Ans. 16—17. Appellants reply that this
reliance on Curd is improper, as Curd “is not cited in a new ground of
rejection.” Reply Br. 2. This is not persuasive, as the Examiner cites Curd
as additional support for the state of prior art knowledge, not as part of the
rejection itself. Cf. Randall Mfg. v. Rea, 733 F.3d 1355, 1362—63 (Fed. Cir.
2013) (prior art references not cited in an obviousness rejection relevant as
evidence of background knowledge to “explain why a skilled artisan would
have been motivated to combine or modify the cited references to arrive at
the claimed inventions”). In contrast, Appellants offer no factual support for
their assertion that “[o]ne skilled in the art would find it particularly
surprising that veltuzumab is effective in treating a patient refractory to
rituximab,” based on sequence similarity. Appeal Br. 13. This is not
persuasive, as “[ajttomey argument is not evidence.” Icon Health & Fitness,
Inc. v. Strava, Inc., 849 F.3d 1034, 1043 (Fed. Cir. 2017).
9 In paragraph 8 of Hansen ’433, the designation “IDEC-C2B8” is used for
rituximab.
10 Curd et al., US 7,820,161, issued Oct. 26, 2010.
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Having considered Appellants’ separate arguments in support of claim
13, we are not persuaded of any reversible error by the Examiner. We affirm
the rejection.
CONCLUSION
Rejections 1 and 3—5 are affirmed. Rejection 2 is affirmed as to
claims 1, 2, 4—12, 14, 16—18, and 21—25, but reversed as to claim 28.
No time period for taking any subsequent action in connection with
this appeal may be extended under 37 C.F.R. § 1.136(a)(l)(iv).
AFFIRMED
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