Ex Parte Godwin

Patent Trial and Appeal Board

Nov 8, 2017

14086702 (P.T.A.B. Nov. 8, 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.
14/086,702 11/21/2013 Antony GODWIN GRT/37-114 1087
23117 7590 11/13/2017
NIXON & VANDERHYE, PC
901 NORTH GLEBE ROAD, 11TH FLOOR
ARLINGTON, VA 22203
EXAMINER
REYNOLDS, FRED H
ART UNIT PAPER NUMBER
1675
NOTIFICATION DATE DELIVERY MODE
11/13/2017 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):
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PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
BEFORE THE PATENT TRIAL AND APPEAL BOARD
Ex parte ANTONY GODWIN
Appeal 2017-001044
Application 14/086,702
Technology Center 1600
Before ERIC B. GRIMES, JEFFREY N. FREDMAN, and
DAVID COTTA, Administrative Patent Judges.
FREDMAN, Administrative Patent Judge.
DECISION ON APPEAL
This is an appeal1 under 35U.S.C. § 134 involving claims to a
chemical compound. The Examiner rejected the claims as obvious. We
have jurisdiction under 35 U.S.C. § 6(b). We reverse.
Statement of the Case
Background
“Many therapeutically active molecules, for example proteins, do not
possess the properties required to achieve efficacy in clinical medical use”
(Spec. 1:9—11). “When proteins clear from the blood circulation quickly
they typically have to be administered to the patient frequently. Frequent
administration further increases the risk of toxicity” (Spec. 1:20—23).
1 Appellant identifies PolyTherics Limited as the Real Party in Interest (see
App. Br. 3).
Appeal 2017-001044
Application 14/086,702
“Water soluble, synthetic polymers, particularly polyalkylene glycols, are
widely used to conjugate therapeutically active molecules such as proteins”
and “have been shown to alter pharmacokinetics favourably by prolonging
circulation time and decreasing clearance rates” (Spec. 1:26—31).
The Specification states that the inventors “have now found a class of
PEGylation reagents which can be used to conjugate molecules including
proteins and peptides to polymers via a single nucleophilic residue, for
example a thiol group, and which have advantages over such commercial
reagents” (Spec. 2:23—26).
The Claims
Claims 1—8 are on appeal. Independent claim 1 is representative and
reads as follows:
1. A compound of the general formula:
X-[NH-CO-Ar-W-(CH=CH)n-CH=CH2]m (Va)
in which X represents a polymer; W represents a keto group; n
represents 0 or an integer of from 1 to 4; m represents an
integer of from 1 to 8; and Ar represents an unsubstituted or
substituted aryl group.
We note that the Examiner entered a Restriction Requirement on June
27, 2014 and Appellant elected the following species of compound for
examination:
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Application 14/086,702
(see Resp. to Restriction Req. 07/15/2014 at 4). We therefore limit our
consideration of the merits of the appealed rejection to the elected species.
See Ex parte Ohsaka, 2 USPQ2d 1460, 1461 (BPAI 1987).
The Issue
The Examiner rejected claims 1—8 under 35 U.S.C. § 103(a) as
obvious over Hunter,2 Hubbell,3 and Balan4 (Final Act. 3—5).
The Examiner finds Hunter teaches:
reacting dyes to textiles (title). One of the two reactions
used is the Michael-type reaction, where a chromophore is
attached to an activating group, which is attached to a double
bond (pi, 1st paragraph). Almost any electron withdrawing
group can be used as an activating group to generate a Michael
acceptor (plO, 3d paragraph), with aromatic ketones being one
of the most reactive groups (pi 1, 4th paragraph), although cost
tends to restrict their use (pi2, 4th paragraph, referring to a
section dealing with costs) and presumably reactivity (p20, 2nd
paragraph). However, the reactive groups are small compared
to the rest of the material, and so are “averaged down” by the
cost of the cargo (pi 9, 4th paragraph), allowing for more
expensive reagents. Note that the only faster reacting electron
withdrawing group is the nitro group, and that does not have a
location to attach a cargo. This indicates that one of the fastest
reacting species would be R- phenyl-CO-CH=CH2, which is
applicant’s elected species if R=PEG-NH-CO.
(Final Act. 3.) The Examiner acknowledges Hunter “does not disclose PEG
attached to the aromatic ring by an amide” (id.).
2 A. Hunter and M. Renfrew, Reactive Dyes for Textile Fibres, 1—209
(Society of Dyers and Colourists 1999) (“Hunter”).
3 Hubbell et al., US 6,958,212 Bl, issued Oct. 25, 2005 (“Hubbell”).
4 Balan et al., Site-Specific PEGylation of Protein Disulfide Bonds Using a
Three-Carbon Bridge, 18 Bioconjugate Chem. 61—76 (2007) (“Balan”).
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Application 14/086,702
The Examiner finds Hubbell teaches “PEG or polysaccharides can be
attached to proteins via Michael-type reaction with amino or mercapto
groups using a vinyl sulfone linker” (id.). The Examiner finds Hubbell
teaches a “wide variety of unsaturated compounds can substitute for the
vinyl sulfone” and “using Michael acceptors to attach PEG to biomolecules,
using a compound with the geometry of the elected species” (id.).
The Examiner finds Balan teaches “similar chemistry as described by
Hunter et al. to attach a PEG to a disulfide bond” (Final Act. 4). The
Examiner finds “PEGylation minimized protein aggregation and increases
protein stability” (id.). The Examiner finds Balan teaches “the reaction of a
sulfhydryl with a Michael’s acceptor where the electron withdrawing group
is an aromatic ketone attached via an amide bond to a PEG” (id.).
The Examiner finds it obvious
to use an aryl ketone as an electron withdrawing group for a
Michael’s type acceptor to attach PEG to a biomolecule, as
described by Hunter et al and Hubbell et al, as this is
exchanging one known element for another yielding expected
results. As Balan et al show the same electron withdrawing
group to attach a PEG to a protein using the same chemistry, an
artisan in this field would use such a group with a reasonable
expectation of success.
(Final Act. 4.)
The issue with respect to this rejection is: Does the evidence of record
support the Examiner’s conclusion that Hunter is analogous art, and in
combination with Hubbell and Balan, renders the elected species obvious?
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Application 14/086,702
Findings of Fact
1. Hunter teaches: “Nucleophilic addition to an activated double
bond is one of the two principal covalent bond formation reactions employed
in commercial reactive dyeing” (Hunter 1).
2. Hunter teaches the “term Michael reaction specifically refers to
the addition of a carbanion to an activated alkene or alkyne.
Heteronucleophilic addition (Scheme 1.1) is called a Michael-type reaction”
(Hunter 6).
3. Hunter teaches that “almost any electron-withdrawing group
can activate an adjacent double or triple bond and generate a Michael
acceptor with the potential of bond formation with the heteronucleophiles
found in natural and synthetic fibres” (Hunter 10).
4. Hunter teaches:
Divalent activating groups are necessary for simple dye
attachment and this eliminates monovalent activators ....
Aromatic esters are more activating than sulphones but
are susceptible to chemical attack in both acid and alkaline
media. Aromatic and aliphatic ketones are highly activating
groups .... [Although ketone is an attractive activating group
from a reactivity point of view, other factors weigh against it.
(Hunter 12.)
5. Hunter teaches the “high reactivities of some Michael acceptors
can lead to storage and handling difficulties for the synthetic organic chemist
working in this field” (Hunter 20).
6. Hubbell teaches: “Nucleophilic addition reactions are used for
the conjugation of the pharmaceutically active compounds to the polymers
to achieve the desirable release rates” (Hubbell 1:17—20).
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Application 14/086,702
7. Hubbell teaches: “Conjugated unsaturated groups, such as vinyl
sulfones (Pathak, supra), have been used to link PEG or polysaccharides to
proteins through Michael-type reactions with amino- or mercaptogroups”
(Hubbell 29:54—58).
8. Hubbell teaches: “It is possible to perform Michael-type
addition reactions on a wide variety of conjugated unsaturated compounds”
(Hubbell 30:15-16).
9. Balan teaches “IFN [Interferon] was then conjugated with 2
equiv of PEG monosulfone 4 to give the three-carbon disulfide double-
bridged PEG-IFN” (Balan 69, col. 2).
10. Figure 1 of Balan is reproduced below:
Sfehctiie t, PrttpstriUKift of PEG Moaosulfane- 4*‘
* f):iO >.>iIPCr NHS: /h) tvmfbvVty -EEC .Ntf -. (oi 5f> nVM jAb^phah: kiAffc-f, pf t '738..
OP5N ^SULFIDE ADDITION - gUMlftATgON SECOND ADDITION BRiOOED
Figure 1. Site-specific PEGylation of a protein disulfide bond.
The disulfide was reduced, and this was followed by reaction
with a monofimctionalized PEG that was capable of sequential,
interactive bis-alkylation. Mechanistically, PEGylation involves
a first thiol addition to a PEG monosulfone followed by sulfmic
acid elimination to generate a second double bond, which then
undergoes a second thiol addition to complete the conjugation.
(Balan 65.)
11. Balan teaches: “the PEGylated molecules intermolecularly
block the attachment of neighboring molecules, causing an apparent
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Application 14/086,702
reduction in the number of binding sites, minimizing protein aggregation,
and increasing protein stability” (Balan 74, col. 2).
Principles of Law
The “analogous art test” governs the question of whether a skilled
artisan would have looked to an unrelated prior art reference. To qualify as
“analogous art” under this test, a reference must be “either in the field of the
applicant’s endeavor or . . . reasonably pertinent to the problem with which
the inventor was concerned in order to rely on [that] reference as a basis for
rejection.” In re Kahn, 441 F.3d 977, 986—87 (Fed. Cir. 2006) {quoted with
approval in KSR Int’l Co. v. Teleflex, Inc., 550 U.S. 398, 418 (2007)).
Analysis
Appellant contends:
Reactive dyes (Hunter) and conjugating agents (Appellant’s
invention) are clearly not in the same field of endeavor. The
cited document is also not reasonably pertinent to Appellant’s
particular problem. In reacting a dye to a textile through an
activating group, Hunter addressed the problem of improving
color fastness by forming a covalent bond between the dye and
the textile’s fibers. Specificity in Hunter’s reaction is not
important, and Hunter contains no significant discussion of the
atoms to which his reagents bind during the dyeing process. In
contrast, the present invention improves the pharmacokinetics
of a drug by conjugating it to a polymer.
(App. Br. 9.)
The Examiner acknowledges “that Hunter et al is from a different
field of endeavor than appellant’s invention,” but contends Hunter
is pertinent to the problem that appellant is attempting to solve.
Hunter et al discusses attaching compounds to molecules using
Michaels acceptors. As shown by Hubbell et al and Balan et al,
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Application 14/086,702
Michaels acceptors are widely used in appellant's field for a
very similar purpose (attaching compounds to biomolecules or
drugs). Logically, a discussion of the chemistry used for these
reactions used for a similar purpose, such as that given by
Hunter et al, would be considered relevant by an individual in
this field.
(Ans. 6.)
We find that Appellant has the better position. Because there is no
dispute that Hunter is not within Appellant’s field of endeavor, the
determinative issue is whether the teachings of Hunter are reasonably
pertinent to the problem sought to be solved.
The Specification identifies the problem to be solved as “many PEG-
maleimides are hydrolytically unstable during storage and conjugation to a
drug candidate. Specifically, a substantial degree of hydrolysis of the
maleimide ring occurs, both prior to and after conjugation” (Spec. 2:17—20).
The Specification identifies the solution as “a class of PEGylation reagents
which can be used to conjugate molecules including proteins and peptides to
polymers via a single nucleophilic residue, for example a thiol group” (Spec.
2:22-25).
We agree with Appellant that Hunter is focused on reacting dyes with
fibers (FF 1, 3) rather than conjugation of drugs or biological molecules with
PEG as in the Specification. “[I]t [is] the burden of the examiner, not
[Appellant], to set forth a prima facie case explaining why a person of
ordinary skill in the art would have been motivated to combine references in
disparate technological fields.” In re Natural Alternatives, LLC, 659 Fed.
Appx. 608, 613—14 (Fed. Cir. 2016) (unpublished). We conclude that the
Examiner’s reasoning that Hunter is pertinent because it teaches “attaching
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Application 14/086,702
compounds to molecules using Michaels acceptors” encompasses too broad
a problem. By the Examiner’s reasoning, Hunter’s covalent methods of
attaching dyes to fibers is pertinent to any covalent attachment mechanism
between any two chemical components, so long as a Michael-type reaction
is involved. We find that reasoning overbroad because the purposes of the
claimed invention and Hunter are very different. See In re Clay, 966 F.2d
656, 659 (Fed. Cir. 1992) (“If [a reference] is directed to a different purpose,
the inventor would accordingly have had less motivation or occasion to
consider it.”).
Because Hunter is necessary for the Examiner’s rejection, we need not
address Appellant’s other arguments that Hubbell is also nonanalogous art
and that unexpected results overcome the prima facie case of obviousness.
Conclusion of Law
The evidence of record does not support the Examiner’s conclusion
that Hunter is analogous art, and in combination with Hubbell and Balan,
renders the elected species obvious.
SUMMARY
In summary, we reverse the rejection of claims 1—8 under 35 U.S.C.
§ 103(a) as obvious over Hunter, Hubbell, and Balan.
REVERSED
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