Ex Parte Chaddock et al

Patent Trial and Appeal Board

Sep 7, 2016

13202696 (P.T.A.B. Sep. 7, 2016)

UNITED STA TES p A TENT AND TRADEMARK OFFICE
APPLICATION NO. FILING DATE
13/202,696 11/07/2011
24728 7590 09/09/2016
MORRIS, MANNING & MARTIN, LLP
IP Department
3343 PEACHTREE ROAD, NE
1600 ATLANTA FINANCIAL CENTER
ATLANTA, GA 30326
FIRST NAMED INVENTOR
John Andrew Chaddock
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.
21027/81411 1887
EXAMINER
SWOPE, SHERIDAN
ART UNIT PAPER NUMBER
1652
NOTIFICATION DATE DELIVERY MODE
09/09/2016 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):
mmmipdocket@system.foundationip.com
tjones@mmmlaw.com
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
BEFORE THE PATENT TRIAL AND APPEAL BOARD
Ex parte JOHN ANDREW CHADDOCK and KEITH ALAN FOSTER
Appeal2016-003643
Application 13/202,696
Technology Center 1600
Before DONALD E. ADAMS, RICHARD J. SMITH, and
JOHN E. SCHNEIDER, Administrative Patent Judges.
ADAMS, Administrative Patent Judge.
DECISION ON APPEAL 1
This appeal under 35 U.S.C. § 134(a) involves claims 1-3, 5, 7-9, 15,
16, 21-23, 27, 28, and 30 (Ans. 2).2 Examiner denied Appellants' claim for
priority to PCT/GB2009/002892 as it relates to claims 9, 23, and 31, and
entered rejections under the judicially-created doctrine of constituting an
improper Markush group and 35 U.S.C. § 103(a).3
1 Appellants identify "[t]he real party in interest [as] Ipsen Bioinnovation
Limited (formerly Syntaxin Limited)" (App. Br. 1 ).
2 Claims 10, 11, 13, 17-20, and 24 stand withdrawn from consideration as
drawn to a non-elected invention (Ans. 2). Pending claims 29 and 31 stand
free from rejection.
3 Appellants withdrew the rejection under 35 U.S.C. § 112, second
paragraph and the provisional obviousness-type double patenting rejection
from this Appeal (see Oral Hearing Transcript 27: 14--20; cf Ans. 9 and 19).
Appeal2016-003643
Application 13/202,696
We have jurisdiction under 35 U.S.C. § 6(b).
We AFFIRM-IN-PART.
STATEMENT OF THE CASE
Appellants' disclosure "relates to non-cytotoxic proteases having
improved efficacy, and to the construction thereof' (Spec. 1 ). Claims 1, 9,
21, 27, and 28 are representative and reproduced in the Claims Appendix of
Appellants' Brief.
Examiner denied Appellants' claim for priority to Chaddock4 as it
relates to claims 9, 23, and 31.
Claims 9, 23, 27, and 28 stand rejected under the judicially-created
doctrine of constituting an improper Markush group.
Claims 1-3, 5, 7, 8, 15, 16, 22, 27, 28, and 30 stand rejected under 35
U.S.C. § 103(a) as unpatentable over Lin. 5
Claim 21 stands rejected under 35 U.S.C. § 103(a) as unpatentable
over the combination of Lin and Foster.6
Priority:
ISSUE
Are Appellants' claims 9, 23, and 31 entitled to claim priority to the
filing date of Chaddock?
ANALYSIS
Appellants' disclose an amino acid sequence having SEQ ID NO: 13
(Spec. 108). Chaddock discloses an amino acid sequence having SEQ ID
4 Chaddock et al., WO 2010/094905 Al (PCT/GB2009/002892), published
Aug. 26, 2010.
5 Lin et al., WO 02/44199 A2, published June 6, 2002.
6 Foster et al., US 2007/0184048 Al, published Aug. 9, 2007.
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Application 13/202,696
NO: 13 (Chaddock 104--105). As Appellants explain, notwithstanding
Examiner's assertion to the contrary, Chaddock's SEQ ID NO: 13 is
"identical to SEQ ID NO: 13 of [Appellants'] application" before this panel
for review (Reply Br. 2; cf Ans. 2). Therefore, notwithstanding Examiner's
assertion to the contrary, Appellants' claims 9, 23, and 31 have an effective
filing date of "December 16, 2009, the filing date of [Chaddock], which
disclosed the recited subject matter" (see Ans. 2).
CONCLUSION OF LAW
Appellants' claims 9, 23, and 31 are entitled to claim priority to the
filing date of Chaddock.
Markush Grouping:
ISSUE
Has Examiner established that Appellants' claims include an improper
Markush grouping?
ANALYSIS
The test for whether a Markush group is proper is whether all of the
compounds in the group have in common a functional utility and a
substantial structural feature disclosed as being essential to that utility. See
In re Harnisch, 631 F.2d 716, 722 (CCPA 1980). As Appellants explain, the
Markush groupings set forth in Appellants' claims meet the criteria set forth
in Harnisch (App. Br. 6-11; Reply Br. 3-5; cf Ans. 11-19). If these criteria
are met, then the Markush group is proper.
CONCLUSION OF LAW
Examiner failed to establish that Appellants' claims include an
improper Markush grouping.
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Application 13/202,696
The rejection of claims 9, 23, 27, and 28 under the judicially-created
doctrine of constituting an improper Markush group is reversed.
Obviousness:
Does the preponderance of evidence relied upon by Examiner support
a conclusion of obviousness?
FACTUAL FINDINGS (FF) [7J
FF 1. Examiner's "diagrammatic comparison of [Appellants' claimed
polypeptide] constructs" and the polypeptide constructs Lin reduced to
practice is reproduced below:
Redted Cons1md ~Cfain1~; l-<1. S,. 7. S. !5. J.6, 22, 23. 27, 28, ;;ind 30)
'~-TQldn P'rotease Domain (LG} .. ,.Toxtn Trn.nslocation Dornain (HN) . .-.:r.;:;i.rgt~ting Domain (Herc
·''c!ea:v~so SNARE -~oteif1:\ ($1:n!loio:om~4i: "!~·s.ull rtiinds !~· !h~ nEil..lfOtl'f ·
Un's Construct
NToxin Protease Domain (LC}._,:ft"J>dn Translocation Domain CHN} .. ,, .. Targeting Dornain (Herc
Examiner's "diagrammatic comparison" illustrates that Appellants' claimed
"constructs comprise an inactivating protease cleavage site that is not in the
7 According to Examiner:
Abbreviations: BoTN; a toxin derived from a Clostridum
botulinum capable of cleaving a specific protein of the SNARE
complex thereby inhibiting exocytosis; Bo TN/ A, type A Bo TN
derived from a C. botulinum; HC, targeting domain; HN,
translocation domain (translocates from the endosome to the
cytosol); LC, catalytic domain; SNARE complex, a series of
proteins comprised within a vesicle- associated or plasma
membrane - associated complex, which are involved in the
exocytic process; factor Xa-thrombin cleaving enzyme.
(Ans. 2, n. 1.)
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Application 13/202,696
targeting domain," whereas "[t]he constructs that Lin ... reduced to practice
comprise an inactivating protease cleavage site in the targeting domain"
(Ans. 20).
FF 2. Examiner finds that Lin's "variants have Bo NT I A activity" until the
protease cleavage "motif is cleaved," which inactivates the variant "because
it cannot bind and be internalized by the target cell" (Ans. 20-21; see Lin 8:
9-10 ("[ w ]hile the presence of the cleavage site itself must permit the toxic
activity to be retained, actual cleavage at the site must result in
inactivation")).
FF 3. Examiner finds that "the only difference between [Appellants'
claimed] polypeptide constructs ... and the polypeptide constructs [] Lin ...
reduced to practice is the location of the inactivating cleavage site" (Ans. 20;
see id. at 21 (Lin "does not reduce to practice a BoNT I A variant having a
secondary protease cleavage motif at a location other than the HC targeting
domain")).
FF 4. Lin discloses that
[i]n designing a thrombin or coagulation factor Xa site into a
botulism toxin, the location of the inserted site is ... such that
the presence of the site will not interfere with activity of the
toxin, but cleavage at the site will destroy or vastly inhibit the
activity of the toxin.
(Lin 9: 6-9; Ans. 21; see also Lin 8: 14--15 ("while the position of the
[cleavage] site should be in a non-critical region with respect to the site
itself, cleavage at that site must have a substantial effect"); Ans. 21 ("Thus,
the functional requirements taught by Lin ... are the same as recited in
[Appellants'] claims"); Ans. 40-41.)
FF 5. Examiner finds that Lin "does not teach a BoNT/A variant
comprising only the catalytic light chain LC and the HN translocation
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domain, wherein the HC binding domain has been replaced with an
exogenous targeting moiety that binds a receptor on the motor neuron" (Ans.
22).
FF 6. Examiner finds that Foster discloses "a polypeptide construct
comprising a non-cytotoxic protease consisting of a BoNT I A variant
comprising the Le catalytic domain and the HN translocation domain ... ,
wherein the HC binding domain has been replaced with a growth factor
targeting moiety, including EGF, that binds a target cell and cleaves a
SNARE protein" (Ans. 22, citing Foster i-fi-f 102, 153, 155, 167-169, and
365-366 (Example 2) and FIGs 4--8).
FF 7. Foster declares that, because Lin does not exemplify a polypeptide
construct with a cleavage site outside of the HC or binding domain (i.e.
Targeting Moiety), Lin "teaches that the only practical site for locating a
secondary protease cleavage site is in the binding domain (i.e. Targeting
Moiety)" (Foster Declaration i-f 10; see id. i-fi-17-11, 14, and 17).
FF 8. Foster declares that "[t]he effect of inserting a cleavage site into the
L chain or the HN translocation domain of Clostridial neurotoxin on the
activity of the neurotoxin could not have been reliably predicted based on
the disclosure in Lin of suitable insertion sites only in the He region" (Foster
Declaration i-f 13).
ANALYSIS
The rejection over Lin:
Based on Lin, Examiner concludes that, at the time Appellants'
invention was made, it would have been prima facie obvious "to make a
panel of BoNT I A variants having a secondary protease cleavage motif in
various positions, including positions not in the HC targeting domain, and
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Application 13/202,696
test said panel for catalytic activity to cleave SNARE protein(s) in target
cells and inactivation by the secondary protease" (Ans. 21 ). In this regard,
Examiner reasons that a person of ordinary skill in this art would have been
motivated to modify Lin's construct in order "to optimize cleavage of
SNARE protein(s) and inactivation by the secondary protease" using known
methods to achieve predictable results (id. at 21-22; see FF 1--4). KSR Int'!
Co. v. Teleflex Inc., 550 U.S. 398, 416 (2007) ("The combination of familiar
elements according to known methods is likely to be obvious when it does
no more than yield predictable results").
Claim 1:
Appellants contend that, notwithstanding Examiner's assertion to the
contrary, "a person of ordinary skill in th[is] art would not have had any
reasonable expectation that a protease cleavage site could be successfully
located in any location other than within the He region or targeting domain"
(App. Br. 18, citing the Foster Declaration8; see FF 7-8). We are not
persuaded. Notwithstanding Appellants' intimation to the contrary, Lin is
not limited to its exemplified disclosure (see Ans. 40 ("[ n ]ow here in Lin ...
is it stated that the only practical site for locating a secondary protease
cleavage site is in the HC targeting domain"); see also Ans. 43--44). In re
Lamberti, 545 F.2d 747, 750 (CCPA 1976) (a reference disclosure is not
limited only to its preferred embodiments, but is available for all that it
discloses and suggests to one of ordinary skill in the art).
On this record, Examiner established that the only limitation Lin
places on the location of the polypeptide construct's cleavage domain is that
8 Declaration of Keith Alan Foster, executed Oct. 16, 2014.
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Application 13/202,696
it is: (a) located at a site that will not interfere with the activity of the toxin
and (b) "will destroy or vastly inhibit the activity of the toxin" when cleaved
(FF 4; see also App. Br. 19; cf Appellants' claim 1). Thus, while Lin
exemplifies polypeptide constructs with cleavage sites within the targeting
domain, Lin does not exclude a cleavage site located at any, non-critical,
location so long as the foregoing requirements are met (see e.g., FF 1--4; see
Ans. 40, citing Lin 6-7, (Lin "teaches how to make and use BoTN variants
having aprotease cleavage motif in a region other than the HC binding
domain")). Therefore, we find no error in Examiner's conclusion that a
person of ordinary skill in this art following Lin's disclosure would have
sought to optimize the location of the cleavage site among a range of regions
across the length of a polypeptide construct (see Ans. 21-22). In re Geisler,
116 F.3d 1465, 1470, (Fed. Cir. 1997) ("'[I]t is not inventive to discover the
optimum or workable ranges by routine experimentation.'") (quoting In re
Aller, 220 F.2d 454, 456 (CCPA 1955)).
In this regard, we agree with Examiner's conclusion that a person of
ordinary skill in this art would have had a reasonable expectation of
successfully identifying cleavage site locations, within the scope of Lin's
disclosure, across the full range of Lin's polypeptide (Ans. 21-22; cf App.
Br. 18-20). "Obviousness does not require absolute predictability of success
... all that is required is a reasonable expectation of success." In re
O'Farrell, 853 F.2d 894, 903 (Fed. Cir. 1988). Therefore, we are not
persuaded by Appellants' contentions to the contrary (see e.g., App. Br. 19
("The effect of inserting a cleavage site into the L chain or the HN
translocation domain [of] a Clostridial neurotoxin on the activity of the
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Application 13/202,696
neurotoxin could not have been reliably predicted based on the disclosure in
Lin of suitable insertion sites only in the He region").
Notwithstanding Appellants' contention to the contrary, a person of
ordinary skill in this art would have recognized that changes in a
polypeptides primary structure may result in secondary and tertiary changes
in the polypeptides structure and that the partial cleavage of a targeting
moiety may not completely inhibit the targeting moiety's ability to bind a
receptor (see generally Ans. 42--45; cf App. Br. 21-22, citing Foster
Declaration 15-16). See In re Jacoby, 309 F.2d 513, 516 (CCPA 1962) (one
skilled in the art must be presumed to know something about the art apart
from what the references disclose); In re Bozek, 416 F.2d 1385, 1390 (CCPA
1969) (conclusion of obviousness may be made "from common knowledge
and common sense of the person of ordinary skill in the art without any
specific hint or suggestion in a particular reference").
Further, it is proper to "take account of the inferences and creative
steps that a person of ordinary skill in the art would employ." KSR, 550 U.S.
at 418. See also id. at 421 ("A person of ordinary skill is also a person of
ordinary creativity, not an automaton."). Thus, as Examiner explains, a
person of ordinary skill in this art would have been motivated to optimize
the location of the cleavage domain, including locating the cleavage domain
outside of the targeting domain, to allow for proper polypeptide folding and
alleviate the concern for latent receptor binding of a partially cleaved
targeting domain (Ans. 21-22). See DyStar Textilfarben GmbH & Co.
Deutschland KG v. C.H. Patrick Co., 464 F.3d 1356, 1367 (Fed. Cir. 2006)
(the "suggestion test is in actuality quite flexible and not only permits, but
requires, consideration of common knowledge and common sense"). For
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the foregoing reasons, we are not persuaded by Appellants' contention that
the "advantages of locating the cleavage site in the L chain or the HN
translocation domain [of] a Clostridial neurotoxin" would not have been
recognized by those of ordinary skill in this art (App. Br. 22; cf Ans. 42,
citing Lin 6-7).
We recognize, but are not persuaded by, Appellants' contentions
regarding Turton,9 which fails to account for Lin's disclosure of the
BoNT/A's structure (see App. Br. 20-21; cf Ans. 42, citing Lin 6-7; see
generally Ans. 43--46).
Claims 27 and 28:
As Appellants explain, Appellants' "Claim 27 [] is directed to
polypeptides as set forth in Claim 1 wherein the cleavage site is located at
specific locations in the protease or translocation domains" (App. Br. 23).
Similarly, Appellants explain that Appellants' "Claim 28 depends from
Claim 1 and recites that the cleavage site is located at specific locations in
the protease or translocation domains" (id. at 24). While, as discussed
above, Lin makes obvious the location of a cleavage site outside of the
targeting domain, Examiner fails to identify an evidentiary basis on this
record to support a conclusion that Lin suggests placing the cleavage site at
any of the specific locations required by Appellants' claims 27 and 28 (see
App. Br. 23-25; see generally Reply Br. 5-9). At best, Examiner simply
concludes that "one or more constructs obvious over Lin ... would, more
likely than not, be encompassed by [Appellants'] Claim 27" and "Claim 28"
9 Turton et al., Botulinum and tetanus neurotoxins: structure, function and
therapeutic utility, 27 TRENDS in Biochemical Sciences 552-58 (2002).
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(Ans. 50 and 51 ). We are not persuaded. Jn re Kahn, 441 F .3d 977, 988
(Fed. Cir. 2006) ("rejections on obviousness grounds cannot be sustained by
mere conclusory statements; instead, there must be some articulated
reasoning with some rational underpinning to support the legal conclusion of
obviousness").
The rejection over the combination of Lin and Foster:
Based on the combination of Lin and Foster, Examiner concludes that,
at the time Appellants' invention was made, it would have been prima facie
obvious
to modify the BoNT I A-derived polypeptide constructs rendered
obvious by Lin ... to incorporate the teachings of Foster ...
wherein polypeptide constructs comprising the LC protease
domain and the HN translocation domain of BoNT I A, an EGF
targeting moiety, and a secondary proterase [sic] cleavage motif
are made.
(Ans. 23.) In this regard; Examiner reasons that a person of ordinary skill in
this art would have been "[m]otivated to [modify Lin's construct as
suggested by Foster] to cleave the SNAP-25 substrate ofBoNT/A at the
motor neuron, as well as in other cells having EGF receptors, and having the
polypeptide construct inactivated upon entry into the blood stream" using
known methods to achieve predictable results (id.; see FF 1-6). See KSR
Int'! Co. v. Teleflex Inc., 550 U.S. at 416.
Appellants' claim 21 depends ultimately from claim 1. Having found
no deficiency in Examiner's reliance on Lin, as it relates to Appellants'
claim 1, we are not persuaded by Appellants' contention that Foster fails to
make up for Appellants' alleged deficiency in Lin (see App. Br. 25).
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CONCLUSION OF LAW
The preponderance of evidence relied upon by Examiner supports a
conclusion of obviousness with respect to the rejection of claim 1 over Lin
and claim 21 over the combination of Lin and Foster.
The rejection of claim 1 under 35 U.S.C. § 103(a) as unpatentable
over Lin is affirmed. Claims 2, 3, 5, 7, 8, 15, 16, 22, and 30 are not
separately argued and fall with claim 1.
The rejection of claim 21under35 U.S.C. § 103(a) as unpatentable
over the combination of Lin and Foster is affirmed.
The preponderance of evidence relied upon by Examiner fails to
support a conclusion of obviousness with respect to the rejection of claims
27 and 28 over Lin. The rejection of claims 27 and 28 under 35 U.S.C.
§ 103(a) as unpatentable over Lin is reversed
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-IN-PART
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