Ex Parte Brown et al

Patent Trial and Appeal Board

Jun 27, 2016

11791498 (P.T.A.B. Jun. 27, 2016)

UNITED STA TES p A TENT AND TRADEMARK OFFICE
APPLICATION NO. FILING DATE FIRST NAMED INVENTOR
111791,498 0512412007 Derek Thomas Brown
20306 7590 06/28/2016
MCDONNELL BOEHNEN HULBERT & BERGHOFF LLP
300 S. WACKER DRIVE
32NDFLOOR
CHICAGO, IL 60606
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.
Cell-0327
(07-994-WO-US)
EXAMINER
GAMBEL, PHILLIP
3017
ART UNIT PAPER NUMBER
1644
MAILDATE DELIVERY MODE
06/28/2016 PAPER
Please find below and/or attached an Office communication concerning this application or proceeding.
The time period for reply, if any, is set in the attached communication.
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
BEFORE THE PATENT TRIAL AND APPEAL BOARD
Ex parte DEREK THOMAS BROWN, HISHANI KIRBY, HELENE
MARGARET FINNEY, and ALASTAIR DAVID GRIFFITHS LA WSON 1
Appeal2013-005641
Application 11/791,498
Technology Center 1600
Before ERIC B. GRIMES, RICHARD J. SMITH, and TA WEN CHANG,
Administrative Patent Judges.
CHANG, Administrative Patent Judge.
DECISION ON APPEAL
This is an appeal under 35 U.S.C. § 134 involving claims to an anti-
TNFa antibody, which have been rejected as anticipated and obvious. We
have jurisdiction under 35 U.S.C. § 6(b).
We reverse.
1 Appellants identify the Real Party in Interest as UCB Celltech. (Appeal
Br. 1.)
Appeal2013-005641
Application 11/791,498
STATEMENT OF THE CASE
"Tumor necrosis factor alpha (TNF a) is a pro-inflammatory cytokine
that is released by and interacts with cells of the immune system." (Spec. 1.)
"TNFa exerts its biological effects through interaction with two structurally
related but functionally distinct cell surface receptors, p55R and p75R[,] that
are co-expressed on most cell types." (Id.) According to the Specification,
the present invention provides an anti-TNFa antibody that "selectively
inhibits TNFa [signaling] through the p55R relative to the p75R." (Id. at 3.)
Claims 1-8 and 11-20 are on appeal. Claims 1 and 12 are illustrative
and read as follows:
1. An anti-TNFa antibody characterised in that the antibody
inhibits TNFa signalling through the p55R to a greater extent than it
inhibits TNFa signalling through the p75R.
12. An anti-TNFa antibody characterised in that the antibody
inhibits TNFa signalling through the p55R to a greater extent than it
inhibits TNFa signalling through the p75R, wherein the ICso for TNFa
signalling through p55R is at least 5 fold lower than the ICso for TNFa
signaling through p75R.
The claims stand rejected as follows:
Claims 1-8 and 11-20 are rejected as anticipated under 35 U.S.C.
§ 102(e) by Babcook,2 as evidenced by Mather3 and Brunner.4
Claims 1-7 and 11-20 are rejected as anticipated under 35 U.S.C.
§ 102( e) by Heavner, 5 as evidenced by Mather and Brunner.
2 Babcook et al., US 7,285,269 B2, issued Oct. 23, 2007.
3 Mather, US 7,148,038 B2, issued Dec. 12, 2006.
4 Brunner et al., US 7,303,885 Bl, issued Dec. 4, 2007.
5 Heavner et al., US 7,250,165 B2, issued Jul. 31, 2007.
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Application 11/791,498
Claims 1-8 and 11-20 are rejected as obvious under 35 U.S.C.
§ 103(a) over the combination of Babcook, Heavner, Peschon,6 Barbara,7
and Sheehan, 8 as further evidenced by Mather and Brunner.
I.
Issue
The Examiner rejected claims 1-8 and 11-20 as anticipated by
Babcook and claims 1-7 and 11-20 as anticipated by Heavner. (Ans. 3.)
Because the same issue is dispositive for both rejections, we address them
together.
With respect to independent claims 1 and 12, the Examiner finds that
Babcook and Heavner each teaches neutralizing TNFa-specific antibodies,
as well as exemplary functional properties and/or epitope mapping
associated with such antibodies. (Sept. 28, 2010 Office Act. 7-8.) The
Examiner further finds that Babcook and Heavner each teaches neutralizing
TNFa-specific antibodies capable of inhibiting binding to p55R. (Id.) The
Examiner concludes that, "[g]iven the epitope specificities and functional
properties of the prior art TNFa-specific antibodies, it would be reasonable
to conclude that the prior art antibodies have the claimed functional
6 Jacques J. Peschon et al., TNF Receptor-Deficient Mice Reveal Divergent
Roles for p55 and p75 in Several Models of Inflammation, 160 J.
IMMUNOLOGY 943 (1998).
7 Jeffrey A.J. Barbara et al., Dissociation of TNF-a cytotoxic and
proinjlammatory activities by p55 receptor- and p75 receptor-selective
TNF-a mutants, 13 THE EMBO J. 843 (1994).
8 Kathleen C. F. Sheehan et al., Monoclonal Antibodies Specific for Murine
p55 and p75 Tumor Necrosis Factor Receptors: Identification of a Novel In
Vivo Role for p75, 181 J. EXPERIMENTAL MED. 607 (1995).
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Application 11/791,498
properties of selective[ly] inhibiting TNFa signaling through p55R relative
to p75R, including the recited degrees of reduction." (Id.)
Appellants contend that neither the Babcook nor the Heavner
disclosures permit a skilled artisan to conclude that the antibodies disclosed
in those references necessarily possess the claimed property regarding
relative inhibition of TNFa signaling vis-a-vis p55R and p75R. (Appeal Br.
3.) Appellants argue that, while the Examiner asserts it is reasonable to
conclude at least some of the prior art antibodies shown to inhibit p55R
signaling would inhibit such signaling to a greater extent than p75R
signaling, inherency requires a showing that the claim elements are
necessarily present in the prior art. (Id. at 2-3.)
The issue with respect to this rejection is whether the evidence of
record supports the Examiner's finding that Babcook and/ or Heavner
inherently discloses an anti-TNFa antibody that inhibits TNFa signaling
through p55R to a greater extent than the signaling through p75R.
Analysis
We agree with Appellants that the Examiner has not established that
either Babcook or Heavner inherently discloses an anti-TNFa antibody that
inhibits signaling through p55R to a greater extent than signaling through
p75R, as required by claims 1 and 12.
The Examiner does not point to any specific antibody disclosed in the
prior art as anticipating. Rather, the Examiner asserts that "it is reasonable
to conclude []at least some of the prior art anti-TNFa antibodies selectively
inhibit at some measurable level [] TNFa signaling through p55R relative to
p75R," because (1) the prior art teaches a number of different anti-TNFa
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Application 11/791,498
antibodies that inhibit p55R signaling by specifically binding to epitopes on
TNFa; (2) specifically binding to an epitope has the meaning of "reacting or
associating more frequently, more rapidly, with greater duration and/or with
greater affinity" with that epitope than others; and (3) the prior art did not
teach that these antibodies also inhibited binding to p75R. (Ans. 9-12.)
In essence, the Examiner asserts that it is probable that the prior art
has disclosed anti-TNFa antibodies with the claimed functional properties.
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." MEHL/Biophile Int'l. Corp. v.
Milgraum, 192 F.3d 1362, 1365 (Fed. Cir. 1999) (quoting In re Oelrich, 666
F.2d 578, 581(CCPA1981)).
The Examiner maintains that products of identical chemical
composition cannot have mutually exclusive properties and that "[ w ]here the
Patent Office has reason to believe that a functional limitation ... may be an
inherent characteristic of the prior art, it has the authority to require the
applicant to prove that the subject matter shown in the prior art does not
possess the characteristics relied on." (Sept. 28, 2010 Office Act. 7; see also
Ans. 12.)
We agree with Appellants, however, that the Examiner has not
provided sufficient basis in evidence or technical reasoning to shift the
burden to Appellants to show a difference between the claimed and prior art
products. The Examiner has not shown that Babcook or Heavner discloses
any particular antibody that is substantially identical (e.g., in variable chain
amino acid sequence) to a claimed antibody. Likewise, while the Examiner
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Application 11/791,498
points out that both the Specification and the prior art disclose obtaining
antibodies through routine immunization with human TNFa and subsequent
screening for desired characteristics (Ans. 7-8), the Examiner provides no
evidence suggesting that antibodies produced through immunization with
human TNFa or those obtained through screening for p55R signaling
inhibition will be substantially identical. Indeed, the evidence of record is to
the contrary, as the Specification shows that not all of the anti-TNFa
antibodies that inhibit p55R signaling inhibit p75R signaling to the same
degree. (Spec. Figs. 4, 6.)
The Examiner also argues that the evidence submitted by Appellants,
including the Brown Declaration,9 do not suffice to rebut a finding of
inherency because the evidence focuses on, e.g., the difficulty of generating
an antibody that inhibits TNFa signaling through p55R without inhibiting
signaling through p75R. The Examiner argues that, in contrast, claims 1 and
12 do not require an antibody that does not inhibit TNFa signaling through
p75R, only one that inhibits such signaling to a lesser degree than it inhibits
signaling through p55R. (Ans. 5-7.) As discussed above, however, in this
case the Examiner has not satisfied the minimum requirements necessary to
shift the inherency burden to Appellants.
In summary, the Examiner has not provided adequate evidence to
support the finding that Babcook or Heavner discloses an antibody meeting
all the limitations of claims 1 and 12. We therefore reverse the anticipation
rejections of claims 1 and 12. Claims 2-8, 11, and 13-20 depend from claim
9 Declaration under 37 C.F.R. § 1.132 of Dr. Derek Brown (Feb. 1, 2012).
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1 or claim 12. Accordingly, we also reverse the rejections of these claims
for the same reasons already discussed.
II.
Issue
The Examiner has rejected claims 1-8 and 11-20 as obvious under
35 U.S.C. § 103(a) over the combination of Babcook, Heavner, Peschon,
Barbara, and Sheehan. (Ans. 3.)
The Examiner finds that, in addition to the teachings set forth in
Babcook and Heavner, Peschon, Barbara, and Sheehan "all provide
additional teachings ... and motivation to make and use neutralizing TNFa-
specific antibodies that distinguish or differentiate between favoring the
neutralization of p55 or p75." (Sept. 28, 2010 Office Act. 9.) The Examiner
concludes that, "[g]iven the clear teachings of the prior art to make and use
neutralizing TNF a-specific antibodies, including [teachings] distinguishing
their effects on p55- /p75-mediated activities [and] the advantages and
utilities associated with ... antibodies that favor blocking p55 over p75; one
of ordinary skill in the art would have been motivated to make and use ...
antibodies that favor blocking p55 over p75 in certain circumstances at the
time the invention was made." (Id.)
The Examiner further concludes that, "[g]iven that the prior art goal
was to make and use neutralizing TNF a-specific antibodies, incorporating
neutralizing TNFa-specific antibodies that favor blocking either p55- or
p75-mediated activities would have been routine ... and therefore obvious
in designing neutralizing TNFa-specific antibodies for various diagnostic
and ... therapeutic utilities." (Id.) Finally, the Examiner concludes that,
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"[f]rom the teachings of the references, it was apparent that one of ordinary
skill in the art would have had a reasonable expectation of success in
producing the claimed invention." (Id.)
Appellants contend that neither Babcook nor Heavner teaches an
antibody with the functional properties recited in the instant claims and that
"one of skill in the art would have no reasonable expectation of success in
creating the claimed antibodies through combination of any of the cited
references or through general knowledge in the art." (Appeal Br. 6-7.) In
particular, Appellants contend that it was understood by those in the field
that the binding interactions of TNFa to p55R and p75R were virtually
identical; thus, there was no basis for hypothesizing that an anti-TNF a
antibody could selectively block one of these receptors relative to the other.
(Id. at 7.)
The issue with respect to this rejection is whether the evidence of
record supports a reasonable expectation of success in creating an antibody
that inhibits TNFa signaling through the p55R to a greater extent than it
inhibits TNFa signaling through the p75R.
Analysis
We agree with Appellants that the evidence of record does not support
a finding of reasonable expectation of success in making the claimed
antibody. As discussed above, the Examiner has not shown that the prior art
disclosed an anti-TNFa antibody that preferentially inhibits TNFa signaling
through p55R relative to p75R.
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Application 11/791,498
To the extent the Examiner relies on Loetscher, 10 which discloses
TNFa mutants that preferentially bind to p55R or p75R, as evidence of
reasonable expectation of success, we are also not persuaded. As we
understand the argument, the Examiner reasons that the existence of TNF a
mutants that preferentially bind to p55R or p75R suggests the presence of
receptor-specific contacts on the TNFa protein and thus, the possibility of
generating anti-TNFa antibodies that preferentially inhibit p55R signaling
by binding to p55R-specific contacts on the TNFa protein. (Ans. 10-11.)
The Brown Declaration explains, however, that a skilled artisan would not
readily expect to be able to create antibodies that selectively inhibit the
binding of TNFa to p55R despite the existence of receptor-specific TNFa
mutants, because the mutations that results in receptor selectivity involve
subtle changes of a few amino acids whereas the surface area where an
antibody binds to a protein is relatively large in comparison. (Brown Deel.
iii! 15-16.)
We recognize that obviousness requires only a reasonable expectation
of success rather than an absolute predictability of success. In re 0 'Farrell,
853 F.2d 894, 903-904 (Fed. Cir. 1988). However, the Examiner has not
explained why, in light of the Brown Declaration, there would have been a
reasonable expectation of success in making an anti-TNFa antibody that
10 Hansruedi Loetscher et al., Human Tumor Necrosis Factor a (TNFa)
Mutants with Exclusive Specificity for the 55-kDa TNF Receptors, 268 THE
J. OF BIOLOGICAL CHEMISTRY 26350-26357 (Dec. 1993). We note that
Loetscher is cited in the Brown Declaration and did not form part of the
obviousness rejection. (Brown Deel. iii! 2-3.) Nevertheless, we address the
Examiner's apparent argument herein for reasons of completeness,
particularly because Barbara also discloses receptor selective TNFa mutants.
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preferentially inhibits p55R signaling, as required by the claims. We are
therefore constrained to reverse the obviousness rejection of claims 1-8 and
11-20.
SUMMARY
We reverse the rejection of claims 1-8 and 11-20 as anticipated by
Babcook and the rejection of claims 1-7 and 11-20 as anticipated by
Heavner. We further reverse the rejection of claims 1-8 and 11-20 as
obvious over the combination of Babcook, Heavner, Peschon, Barbara, and
Sheehan.
REVERSED
10