Ex Parte Saltiel et al

Patent Trial and Appeal Board

Mar 13, 2017

12411226 (P.T.A.B. Mar. 13, 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.
12/411,226 03/25/2009 Alan Saltiel UM-30365/US-2/ORD 4743
72960 7590 03/15/2017
Casimir Jones, S.C.
2275 DEMING WAY, SUITE 310
MIDDLETON, WI 53562
EXAMINER
WANG, SHENGJUN
ART UNIT PAPER NUMBER
1627
NOTIFICATION DATE DELIVERY MODE
03/15/2017 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):
docketing @ c asimirj ones .com
pto.correspondence@casimirjones.com
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
BEFORE THE PATENT TRIAL AND APPEAL BOARD
Ex parte ALAN SALTIEL, MERLIJN BAZUINE,
SHIAN-HUEY CHIANG, and CAREY LYMENG
Appeal 2016-002426
Application 12/411,226
Technology Center 1600
Before JEFFREY N. FREDMAN, TAWEN CHANG, and
JOHN E. SCHNEIDER, Administrative Patent Judges.
FREDMAN, Administrative Patent Judge.
DECISION ON APPEAL
This is an appeal1 under 35U.S.C. § 134 involving claims to a method
of treating impaired insulin signaling or reducing or preventing the increase
of body fat. The Examiner rejected the claims as not enabling the full scope
of the claims and as anticipated. We have jurisdiction under 35 U.S.C.
§ 6(b). We reverse and enter a New Ground of Rejection.
1 Appellants identify the Real Party in Interest as the Regents of the
University of Michigan (see App. Br. 3).
Appeal 2016-002426
Application 12/411,226
Statement of the Case
Background
“[Tjhere is an urgent need for a more comprehensive understanding of
the molecular basis of obesity and diabetes . . . and for more effective
pharmaceuticals for preventing and treating the diseases without undesirable
side effects” (Spec. 2:3—7).
“[T]he present invention provides methods of treatment comprising:
administering an IKKi inhibitor to a subject with a condition associated with
impaired insulin receptor signaling” (Spec. 2:15—32).
The Claims
Claims 1—3, 6—9, 12, and 13 are on appeal. Claim 1 is representative
and reads as follows:
1. A method of treating impaired insulin signaling comprising:
a) providing a subject experiencing or at risk for impaired
insulin signaling; and
b) administering to said subject a therapeutically effective dose
of an IKKi-inhibiting agent, wherein said administration results in
improved insulin signaling in said subject.
The issues
A. The Examiner rejected claims 1—3, 6—9, 12, and 13 under 35 U.S.C.
§ 112, first paragraph, scope of enablement (Ans. 2—6).
B. The Examiner rejected claims 1—3, 6—9, 12, and 13 under 35 U.S.C.
§ 102(b) as anticipated by Bamborough2 (Ans. 6—7).
2 Bamborough et al, WO 2005/075465 Al, published Aug. 18, 2005
(“Bamborough”).
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A. 35 U.S.C. § 112, scope of enablement
The issue with respect to this rejection is: Does the evidence of record
support the Examiner’s conclusion that the Specification does not enable the
full scope of the claimed invention?
Findings of Fact
Breadth of Claims
1. Claim 1 is broadly drawn to treatment of impaired insulin
signaling by administration of any agent that inhibits IKKi (see Claim 1).
Claim 8 is broadly drawn to reducing body fat or preventing increase in
body fat in a subject by administering any agent that inhibits IKKi (see
Claim 8).
2. The Specification teaches: “In some embodiments, the
condition treated is obesity. In other embodiments, the condition treated is
diabetes (e.g., type I, or type II, or both types I and II)” (Spec. 2:31—32).
Presence of Working Examples
3. The Specification has no working examples of IKKI inhibitors,
but teaches when the “IKKi gene was deleted in mice by homologous
recombination . . . IKKi knockout mice (IKKiKO) gained significantly less
weight than did their wildtype littermates” (Spec. 77:26—29).
Amount of Direction or Guidance Presented
4. The Specification teaches:
Both Types 1 and 2 diabetes mellitus are disorders of
dysregulated energy metabolism, due to inadequate action
and/or secretion of insulin. Although it is more common in
Type 2, patients with both forms of diabetes exhibit insulin
resistance, resulting from a defect in insulin-stimulated glucose
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Application 12/411,226
transport in muscle and fat and suppression of hepatic glucose
output.
(Spec. 52:22-26).
5. The Specification teaches: “In further embodiments, the
reduction in body fat is a result of increased glucose metabolism caused by
the IKKi inhibitor. In some embodiments, the reduction in body fat is caused
by increased insulin receptor signaling” (Spec. 3:20-23).
6. The Specification teaches:
Exemplary agents that inhibit IKKi expression or activity
include small interfering RNAs (siRNAs), ribozymes, antisense
nucleic acids, kinase inhibitors, anti-IKKi antibodies, small
molecules, peptides, mutant IKKi polypeptides and the like. In
some embodiments, the IKKi inhibitor is an nucleic acid
sequence that can inhibit the functioning of an IKKi RNA (e.g.,
such as the sequences shown in Figures 24 and 25).
(Spec. 41:21-25).
7. The Specification teaches: “In certain embodiments, the IKKi
inhibitor is a small molecule. For example, in particular embodiments, the
IKKi inhibitor is 5-(5,6-Dimethoxy-lH-benzimidazol-l-yl)3-[[2-
(methylsulfonyl)phenyl] methoxy] -2 -thiophenecarbonitrile. In particular
embodiments, the IKKi inhibitor is a benzimidazol substituted thiopene
derivative, such as those described in W02005/075465” (Spec. 44:11—15).
8. The Specification teaches:
Various commercially available anti-IKKi antibodies may be
employed with the methods and compositions of the present
invention. Exemplary antibodies include, but are not limited to:
mouse monoclonal antibody 107A1458 from Abeam; mouse
monoclonal antibody 728587 from Abeam . . . rabbit anti-
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Application 12/411,226
human polyclonal antibody 701-716 from Calbiochem; and
mouse monoclonal antibody 107A1458 from Imgenix.
(Spec. 47:12-18).
State of the Prior Art and Unpredictability of the Art
9. The Examiner states “the pharmaceutical art is unpredictable”
(Ans. 3), but provides no specific evidence of unpredictability regarding
IKKi inhibiting agents.
10. Bamborough teaches
benzimidazole derivatives are potentially useful in the treatment
of diseases associated with inappropriate I-kappa-B kinase-3
(IKK3) (also known as I-kappa-B kinase epsilon (IKKa) or
inducible I-kappa B kinase (IKKi)) activity, including in
particular in the treatment and prevention of disease states
mediated by IKK3 mechanisms including inflammatory and
tissue repair disorders, particularly . . . diabetes.
(Bamborough 1:6—16).
11. The Olefsky3 Declaration states: “It is clear to me, and would
certainly have been clear to one of ordinary skill in the art. . . that any
inhibition of IKKi would result in improved insulin signaling in a subject
what had been experiencing impaired insulin signaling” (Olefsky Deck 13).
Quantity of Experimentation
12. The Examiner finds a “[ljarge quantity of experiment would be
necessary as searching for the inhibitor would be a process of [trial and
error]” (Ans. 3), but provides no specific evidence regarding the quantity of
experimentation necessary.
3 Declaration of Dr. Jerrold M. Olfesky, dated May 26, 2014
(“Olefsky Decl.”).
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Skill in the Art
13. The Examiner finds a “skilled artisan practicing the claimed
invention would likely be a physician or other clinician with an advanced
medical degree” (Ans. 4).
Principles of Law
Factors to be considered in determining whether a disclosure
would require undue experimentation . . . include (1) the
quantity of experimentation necessary, (2) the amount of
direction or guidance presented, (3) the presence or absence
of working examples, (4) the nature of the invention, (5) the
state of the prior art, (6) the relative skill of those in the art,
(7) the predictability or unpredictability of the art, and (8)
the breadth of the claims.
In re Wands, 858 F.2d 731, 737 (Fed. Cir. 1988).
Analysis
While claims 1 and 8 are broadly drawn to any IKKi-inhibiting agent,
there is no evidence of unpredictability regarding IKKi-inhibiting agents (FF
9) or of a large quantity of experimentation necessary to practice the claimed
invention (FF 12). By contrast, there is evidence of known small molecule
IKKi inhibiting agents (FF 10), the Specification provides substantial
guidance on IKKi-inhibiting agents in general (FF 4—8), and the skill in the
art is high (FF 13).
The Examiner has provided insufficient evidence on this record that
undue experimentation would have been required to enable the full scope of
the claims, and therefore, as we balance the Wands factors, we conclude the
evidence does not support the scope of enablement rejection.
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Conclusion of Law
The evidence of record does not support the Examiner’s conclusion
that the Specification does not enable the full scope of the claimed invention.
B. 35 U.S.C. 102(b) over Bamborough
The issue with respect to this rejection is: Does the evidence of
record support the Examiner’s conclusion that Bamborough anticipates
claims 1 and 8?
Principles of Law
The Examiner bears the initial burden of establishing a prima facie
case of anticipation. In re King, 801 F.2d 1324, 1326—27 (Fed. Cir. 1986).
Analysis
The Examiner finds Bamborough “teaches the small molecules IKKi
(IKK3) inhibitors . . . benzimidazol substituted thiopene derivatives, and
method of using the same for treating diabetes” (Ans. 6). The Examiner
finds that “when a species is clearly named, the species claim is anticipated
no matter how many other species are additionally named” (Ans. 9).
Appellants contend “Bamborough et al. does not teach administering
IKKi-inhibiting agents to a subject (1) experiencing or at risk for impaired
insulin signaling, or (2) experiencing or at risk of overweight or obese body
composition” (App. Br. 12).
We find that Appellants have the better position because there is no
evidence that diabetes is identical to “impaired insulin signaling” as recited
in claim 1 or to “reducing body fat or preventing increase in body fat” as
recited in claim 8. We don’t agree with Appellants that Bamborough limits
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diabetes to an autoimmune disorder because, before diabetes on the list,
Bamborough mentions stroke, and after diabetes, Bamborough lists cancer
and AIDS, none of which are normally considered autoimmune diseases.
However, Appellants’ Specification clarifies that not all diabetes
patients have “impaired insulin signaling.” In particular, the Specification
teaches that impaired insulin signaling is a dysregulation more common in
type 2 diabetes patients than type 1 patients (FF 4), which evidences that the
diabetes patient population with “impaired insulin signaling” differs from
populations with inadequate “action and/or secretion of insulin” (FF 4).
Similarly, the Specification teaches that sometimes “reduction in body fat is
a result of increased glucose metabolism” and sometimes “reduction in body
fat is caused by increased insulin receptor signaling” (FF 5).
This reasoning that diabetes does not inherently result from “impaired
insulin signaling” and that treatment of diabetes will not necessarily reduce
or prevent the increase of body fat, is consistent with Perricone, which
distinguished between the topical application of a lotion to skin generally to
prevent sunburn, and the topical application of a lotion to treat sunburned
skin, finding that the “issue is not. . . whether [the prior art] lotion if applied
to skin sunburn would inherently treat that damage, but whether Pereira
discloses the application of its composition to skin sunburn. It does not.”
Perricone v. Medicis Pharm. Corp., 432 F.3d 1368, 1378 (Fed. Cir. 2005).
The same analysis applies here. There is a general teaching in
Bamborough to treat diabetes patients with benzimidazol substituted
thiopene IKKi-inhibitors, and if those same diabetes patients also happened
to have impaired insulin signaling, the treatment might also necessarily
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result in treatment of the impaired insulin signaling or reduce body fat by
increasing insulin receptor signaling, analogous to the skin treatment at issue
in Perricone. However, the Examiner has not identified any teaching or
suggestion in Bamborough to treat impaired insulin signaling itself, or to
reduce or prevent the increase of body fat, with the IKKi-inhibitors. In the
same manner that not everyone who applies lotion to his or her skin will
necessarily have sunburn, not all diabetes patients will necessarily have
impaired insulin signaling and therefore the treatment will not necessarily
result in inherent treatment of impaired insulin signaling or reduce or
prevent the increase of body fat. In re Oelrich, 666 F.2d 578, 581 (C.C.P.A.
1981) (“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.”).
Conclusion of Law
The evidence of record does not support the Examiner’s conclusion
that Bamborough anticipates claims 1 and 8.
New Ground of Rejection
Under the provisions of 37 C.F.R. § 41.50(b), we enter the
following new grounds of rejection.
Claims 1—3, 6—9, 12, and 13 are rejected under 35U.S.C. § 112, first
paragraph as failing to comply with the written description requirement.
We frame the written description issue before us as follows: Does the
evidence of record support the conclusion that the Specification fails to
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provide descriptive support for treatment of impaired insulin signaling with
“an IKKi-inhibiting agent” as broadly recited in claims 1 and 8?
Principles of Law
[T]he hallmark of written description is disclosure.... [T]he test
requires an objective inquiry into the four comers of the
specification from the perspective of a person of ordinary 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.
AriadPharmaceuticals, Inc. v. EliLilly and Co., 598 F.3d 1336, 1351 (Fed.
Cir. 2010).
Analysis
[T]he inventor cannot lay claim to that subject matter unless he
can provide a description of the compound sufficient to
distinguish infringing compounds from non-infringing
compounds, or infringing methods from non-infringing
methods. As the district court observed, “[t]he claimed method
depends upon finding a compound that selectively inhibits
PGHS-2 activity. Without such a compound, it is impossible to
practice the claimed method of treatment.”
University of Rochester v. G.D. Searle & Co., 358 F.3d 916, 926 (Fed. Cir.
2004).
Claim 1, as interpreted in light of the Specification, is broadly drawn
to treatment of impaired insulin signaling with any IKKi-inhibiting agent.
Similarly, claim 8 is broadly drawn to reducing body fat or preventing
increase in body fat with any IKKi-inhibiting agent. The Specification
therefore must adequately describe that genus of compounds.
The written description requirement can be met by disclosing
“complete or partial structure, other physical and/or chemical properties,
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functional characteristics when coupled with a known or disclosed
correlation between function and structure, or some combination of such
characteristics.” Enzo Biochem, Inc. v. Gen-Probe Inc., 323 F.3d 956, 964
(Fed. Cir. 2002).
In this case, the Specification and prior art of Bamborough provide
specific structures of a single small molecule type of IKKi-inhibiting agent,
benzimidazole derivatives (FF 6, 9). The Specification also generically lists
other agents, “small interfering RNAs (siRNAs), ribozymes, antisense
nucleic acids, kinase inhibitors, anti-IKKi antibodies, small molecules,
peptides, mutant IKKi polypeptides” (FF 5; cf. FF 7).
The Specification does not, however, demonstrate that any of the
other listed agents has any effect on IKKi, either in vitro, in tissue culture, or
in vivo. The present case is therefore analogous to Ariad and Rochester. In
Rochester, the patent claimed a method of selectively inhibiting the enzyme
PGHS-2 (also known as COX-2) by “administering a non-steroidal
compound that selectively inhibits activity of the PGHS-2 gene product to a
human.” Rochester, 358 F.3d at 918. The patent “describes in detail how to
make cells that express either COX-1 or COX-2, but not both ..., as well as
‘assays for screening compounds, including peptides, polynucleotides, and
small organic molecules to identify those that inhibit the expression or
activity of the PGHS-2 gene product.”’ Rochester, 358 F.3d at 927.
The Court held that “[e]ven with the three-dimensional structures of
enzymes such as COX-1 and COX-2 in hand, it may even now not be within
the ordinary skill in the art to predict what compounds might bind to and
inhibit them.” Rochester, 358 F.3d at 925. There is no evidence of record in
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the instant Specification that prediction of compounds which bind to and
inhibit IKKI was within the ordinary skill in the art at the time this invention
was filed.
As in Rochester, the present application discloses the assay for
screening for compounds that act as selective inhibitors of IKKi but fails to
provide any mode of identification other than trial and error (see Spec. 47:20
to 52:9; specifically “For example, a test cell can be contacted with a
candidate agent and then the cells can be lysed to produce a cellular lysate.
The IKKi IR kinase activity in the cellular lysate can be assessed with an in
vitro kinase assay to determine if the candidate agent increased or decreased
the IKKi IR kinase activity within the cell” Spec. 48:10—13).
As the district court pointed out: Tellingly, ... what plaintiffs
experts’ [sic] do not say is that one of skill in the art would,
from reading the patent, understand what compound or
compounds-which, as the patent makes clear, are necessary to
practice the claimed method-would be suitable, nor would one
know how to find such a compound except through trial and
error .... Plaintiffs experts opine that a person of ordinary skill
in the art would understand from reading the ’850 patent what
method is claimed, but it is clear from reading the patent that
one critical aspect of the method—a compound that selectively
inhibits PGHS-2 activity—was hypothetical, for it is clear that
the inventors had neither possession nor knowledge of such a
compound.
Rochester, 358 F.3d at 925—926. Here, the Specification and prior art teach
one small molecule type inhibitor (FF 6, 9), but all other inhibitors, whether
small molecule, peptide, protein, antibody, or RNA, are hypothetical and
would have required trial and error screening.
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Ariad shares similar facts, where the “only example of a specific
inhibitor given in the specification is I-kB . . . and [an expert testified] that
one of ordinary skill could through experimentation isolate natural I-kB.”
Ariad, 598 F.3d at 1356. Ariad found that for other inhibitors, “[i]n the
context of this invention, a vague functional description and an invitation for
further research does not constitute written disclosure of a specific
inhibitor.” Id. We find that the same result obtains in the instant situation,
where a broad claim to treatment with an IKKi inhibitor is not sufficient to
describe every such inhibitor given a Specification that discloses one
working class of IKKi inhibitors and suggests that other molecules may be
screened and identified as inhibitors but fails to demonstrate possession of
any such other IKKi inhibitors. See LizardTech, Inc. v. Earth Res. Mapping,
Inc., 424 F.3d 1336, 1345 (Fed.Cir.2005) (holding that “[a]fter reading the
patent, a person of skill in the art would not understand” the patentee to have
invented a generic method where the patent only disclosed one embodiment
of it).
We therefore find the evidence of record supports the conclusion that
the Specification fails to provide descriptive support for treatment of
impaired insulin signaling with “an IKKi-inhibiting agent” as broadly recited
in claims 1 and 8.
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SUMMARY
In summary, we reverse the rejection of claims 1—3, 6—9, 12, and 13
under 35 U.S.C. § 112, first paragraph, scope of enablement.
We reverse the rejection of claims 1—3, 6—9, 12, and 13 under
35 U.S.C. § 102(b) as anticipated by Bamborough.
In a new ground of rejection, we reject claims 1—3, 6—9, 12, and 13
under 35 U.S.C. § 112, first paragraph as failing to comply with the written
description requirement.
This decision contains a new ground of rejection pursuant to 37
C.F.R. § 41.50(b). Section 41.50(b) provides “[a] new ground of rejection
pursuant to this paragraph shall not be considered final for judicial review.”
Section 41.50(b) also provides:
When the Board enters such a non-final decision, the
appellant, within two months from the date of the decision,
must exercise one of the following two options with respect to
the new ground of rejection to avoid termination of the appeal
as to the rejected claims:
(1) Reopen prosecution. Submit an appropriate
amendment of the claims so rejected or new Evidence relating
to the claims so rejected, or both, and have the matter
reconsidered by the examiner, in which event the prosecution
will be remanded to the examiner. The new ground of rejection
is binding upon the examiner unless an amendment or new
Evidence not previously of Record is made which, in the
opinion of the examiner, overcomes the new ground of rejection
designated in the decision. Should the examiner reject the
claims, appellant may again appeal to the Board pursuant to this
subpart.
(2) Request rehearing. Request that the proceeding be
reheard under § 41.52 by the Board upon the same Record. The
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request for rehearing must address any new ground of rejection
and state with particularity the points believed to have been
misapprehended or overlooked in entering the new ground of
rejection and also state all other grounds upon which rehearing
is sought.
Further guidance on responding to a new ground of rejection can be
found in the Manual of Patent Examining Procedure § 1214.01.
REVERSED; 37 C.F.R, $ 41.50(b)
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