Ex Parte Murakami et al

Patent Trial and Appeal Board

Oct 3, 2016

13503357 (P.T.A.B. Oct. 3, 2016)

UNITED STA TES p A TENT AND TRADEMARK OFFICE
APPLICATION NO. FILING DATE
13/503,357 04/20/2012
25225 7590 10/05/2016
MORRISON & FOERSTER LLP
12531 HIGH BLUFF DRIVE
SUITE 100
SAN DIEGO, CA 92130-2040
FIRST NAMED INVENTOR
Hidehiro Murakami
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.
643102001600 1732
EXAMINER
EWOLDT, GERALD R
ART UNIT PAPER NUMBER
1644
NOTIFICATION DATE DELIVERY MODE
10/05/2016 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):
PatentDocket@mofo.com
EOfficeSD@mofo.com
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
BEFORE THE PATENT TRIAL AND APPEAL BOARD
Ex parte HIDEHIRO MURAKAMI, HIROFUMI Y AMANISHI, and
MORIKAZU ONJI1
Appeal2014-008628
Application 13/503,357
Technology Center 1600
Before JOHN G. NEW, RICHARD J. SMITH, and
DEVON ZASTROW NEWMAN, Administrative Patent Judges.
SMITH, Administrative Patent Judge.
DECISION ON APPEAL
This is an appeal under 35 U.S.C. § 134 involving a claim to a method
for treating inflammatory bowel disease (IBD). We have jurisdiction under
35 U.S.C. § 6(b).
We affirm.
1 According to Appellants, the real party in interest is National University
Corporation Ehime University. (Appeal Br. 2.)
Appeal2014-008628
Application 13/503,357
STATEMENT OF THE CASE
Background
"An inflammatory bowel disease (IBD), including Crohn's disease
and ulcerative colitis, is a disease characterized by an impaired immune
system in the intestinal tract." (Spec. i-f 2.)
"The inventors of the present invention revealed that carbonic
anhydrase I (i.e., CA I) and a CA I-pulsed regulatory dendritic cell have an
antigen-specific therapeutic effect on inflammatory bowel disease in a model
mouse, and thus completed the present invention." (Id. i-f 7.)
Claim on Appeal
Claim 16 is on appeal, and reads as follows:
16. A method for treating inflammatory bowel disease, comprising
administering to a subject in need of such treatment an amount of carbonic
anhydrase I effective to treat or prevent said inflammatory bowel disease.
(Claims Appendix, Appeal Br. 7.)
Examiner's Rejections
1. Claims 16 stands rejected under 35 U.S.C. § 112, first paragraph, as
failing to comply with the enablement requirement. (Ans. 2.)
2. Claim 16 stands rejected under 35 U.S.C. § 103(a) as unpatentable
over Rodriguez2 and Roessner. 3 (Id. 6.)
2 Rodriguez, US 7,858,602 B2, issued Dec. 28, 2010 ("Rodriguez").
3 Roessner et al., Oxidative stress in ulcerative colitis-associated
carcinogenesis, Pathology- Research and Practice 204, 511-24 (2008)
("Roessner").
2
Appeal2014-008628
Application 13/503,357
FINDINGS OF FACT
We adopt as our own the Examiner's findings and analysis concerning
the scope and content of the prior art. The following findings are included
for emphasis and reference convenience.
FF 1. The Specification states that "[t]he term 'inflammatory bowel disease'
refers to a disease characterized by chronic persistent enteritis, and includes
ulcerative colitis, Crohn's disease and the like." (Spec. i-f 16.)
FF 2. The Specification states that "[t]he oral administration of CA I
improved enteritis of the CD4+CD25-T cell-transplanted inflammatory
bowel disease model mouse." (Id. i-f 88.)
FF 3. Rodriguez teaches that by administering carbonic anhydrase enzymes,
including CA I, "diseases associated with oxidative stress can be prevented
or treated." (Rodriguez col. 11, 11. 38--41 and 52-54.)
FF 4. Rodriguez teaches a number of diseases or conditions associated with
oxidative stress, including lupus and multiple sclerosis. (Id. col. 12, 11. 5-
12.)
FF 5. Roessner teaches that "[ o ]xidative stress has long been associated
with the pathogenesis of chronic inflammatory bowel disease (IBD)-related
colorectal cancer." (Roessner Abstract.)
3
Appeal2014-008628
Application 13/503,357
DISCUSSION
Issue No. 1: Enablement
Whether a preponderance of the evidence of record supports the
Examiner's conclusion that claim 16 fails to satisfy the enablement
requirement.
Principles of Law
"A lack of enablement rejection under section 112, i-f 1 is appropriate
where the written description fails to teach those in the art to make and use
the invention as broadly as it is claimed without undue experimentation." In
re Cortright, 165 F.3d 1353, 1356 (Fed. Cir. 1999).
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
The Examiner concluded that claim 16 fails to satisfy the enablement
requirement because, due to
the quantity of experimentation necessary, the lack of sufficient
guidance in the specification, the lack of sufficient working
examples, i.e., the specification discloses only the alleged
induction of tolerance in an inbred experimental animal model,
the unpredictability of the art, and the breadth of the claims, it
would take undue trials and errors to practice the claimed
invention.
(Ans. 5.)
4
Appeal2014-008628
Application 13/503,357
The Examiner supported this conclusion with a number of references4
illustrating the unpredictability of, and difficulty in producing, tolerance-
inducing immunotherapy in human trials. (Id. at 2-5.) The Examiner's
obviousness conclusion was thus based on lack of enablement for the full
scope of claim 16. See Cortwright, 165 F.3d at 1356 (discussing forms of
the enablement rejection, including "that the specification does not enable
one of ordinary skill to use the invention commensurate with the scope of
the claims").
Appellants point to the Specification as demonstrating "a mouse
model for IBD." (Appeal Br. 2, citing Spec. i-fi-186-88; FF 2.) Appellants
also rely on Feldman (discussed by the Examiner) and several other
references5 to argue that "clearly it is not inevitable that efforts to induce
4 The articles referred to by the Examiner are (1) Autoimmune shares
collapse on Coll oral data in rheumatoid arthritis, Marketletter Pub. Ltd.
(1999) ("iviarketletter"); (2) Pozzilli et al., lvo effect of oral insulin on
residual beta-cell function in recent-onset Type I diabetes (the IMDIAB VII),
Diabetologia 43, 1000--04 (2000) ("Pozzilli"); (3) Skyler et al., Effects of
Oral Insulin in Relatives of Patients with Type I Diabetes, 28 Diabetes Care
5, 1068-76 (2005) ("Skyler"); (4) Goodnow, Pathways for self-tolerance
and the treatment of autoimmune diseases, The Lancet 357, 2115-21 (2001)
("Goodnow"); (5) Dong et al., Transplantation tolerance: The concept and
its applicability, Pediatric Transplantation 3, 181-92 ( 1999) ("Dong"); ( 6)
Bell et al., In Trans T Cell Tolerance Diminishes Autoantibody Responses
and Exacerbates Experimental Allergic Encephalomyelitis, J. Immunol. 180,
1508-16 (2008) ("Bell"); and (7) Feldman et al., Design of effective
immunotherapy for human autoimmunity, Nature 435, 612-19 (2005)
("Feldman").
5 The articles referred to by Appellants are (1) Margalit et al., A Double-
Blind Clinical Trial for Treatment of Crohn 's Disease by Oral
Administration of AlequelfM, A Mixture of Autologous Colon-Extracted
Proteins: A Patient-Tailored Approach, Am. J. Gastroenterology 101, 561-
5
Appeal2014-008628
Application 13/503,357
imnmnotolerance in humans (which is the postulated mechanism here) are
failures" and "that there is no reason to think that success in animal models
will inevitably predict failure in humans." (Appeal Br. 3--4.) Appellants
also argue that the holding in In re Brana, 51F.3d1560 (Fed. Cir. 1995),
controls the enablement determination, and that claim 16 "does not require
prevention." (Appeal Br. 3; Reply Br. 2--4.)
We find that the Examiner has the better position. In reaching that
conclusion, we are guided primarily by a consideration of the working
example (model mouse), the breadth of claim 16, and the unpredictability of
the art (Wands factors 3, 7, and 8). See Enzo Biochem, Inc. v. Calgene, Inc.,
188 F.3d 1362, 1371 (Fed. Cir. 1999) ("all of the [Wands] factors need not
be reviewed when determining whether a disclosure is enabling").
Working Example
The mouse model for IBD referred to by Appellants comprises the
oral administration of mCAl (mouse CA I) to a T cell-transplanted enteritis
model mouse, and comparing the results to a control mouse. (Spec. i-fi-186-
88; FF 2.) Based on the results of that comparison, Appellants conclude,
among other conclusions, that "the oral administration of CA I exerts
depressant effect on enteritis in inflammatory bowel disease model mouse."
(Id. i189.) Appellants do not discuss these test results in their briefing, but
68 (2006) ("Margalit"); (2) Trentham et al., Effects of Oral Administration
of Type II Collagen on Rheumatoid Arthritis, Science 261, 1727-30 (1993)
("Trentham"); (3) Weiner et al., Double-Blind Pilot Trial of Oral
Tolerization with Myelin Antigens in Multiple Sclerosis, Science 259, 1321-
24 (1993) ("Weiner"); and (4) Fourlanos et al., Evidence That Nasal Insulin
Induces Immune Tolerance to Insulin in Adults With Autoimmune Diabetes,
Diabetes 60, 1237--45 (2011) ("Fourlanos").
6
Appeal2014-008628
Application 13/503,357
simply argue that "demonstration of effectiveness in an animal model is
adequate to support compliance with [the enablement] section" based on In
re Brana, 51F.3d1560 (Fed. Cir. 1995). (Appeal Br. 3.)
Appellants' sole reliance on their mouse model and Brana is
misplaced. The court in Brana addressed the requirement that a claimed
invention have utility. Id. at 1564---68. While the "how to use" prong of
section 112 incorporates the requirement that the specification disclose a
practical utility for the invention, an enabling disclosure must also
adequately disclose to one of ordinary skill in the art how to use the
invention without undue experimentation. Cortright, 165 F.3d at 1356.
This is evidenced by cases in which working examples alone were
insufficient to satisfy the enablement requirement. See In re Vaeck, 947
F.2d 488, 495 (Fed. Cir. 1991) ("[t]here is no reasonable correlation between
the narrow disclosure in appellants' specification and the broad scope of
protection sought in the claims"); In re Wright, 999 F.2d 1557, 1562 (Fed.
Cir. 1993) ("the PTO set forth a reasonable basis for finding that the scope
of the appealed claims is not enabled by the general description and the
single working example").
Breadth of Claim 16
Claim 16 recites a method for treating IBD. (Appeal Br. 7.) The
definition of IBD includes at least several diseases "characterized by chronic
persistent enteritis." (FF 1.)
The claimed method comprises "administering to a subject in need of
such treatment an amount of carbonic anhydrase I." (Appeal Br. 7.) The
"subject" in claim 16 is not defined in the Specification, but invariably
includes a human. (See Appeal Br. 3.) Furthermore, carbonic anhydrase I is
7
Appeal2014-008628
Application 13/503,357
broadly described in the Specification as essentially any polypeptide or
protein "as long as it is able to induce the CA I-specific imnmnogenic
antigen presentation cell." (Spec. i-f 11.)
Claim 16 further recites that the amount of CA-I is "effective to treat
or prevent said inflammatory bowel disease." (Appeal Br. 7.) At least with
regard to a "patient," the Specification provides a broad description of
possible dosage forms, amounts, and regimens, stating that "[t]he
administration is not particularly limited as long as the desirable therapeutic
or preventive effect can be obtained." (Spec. i-f 22.) Moreover, neither the
term "treat" nor the term "prevent" are defined in the Specification. The
broadest reasonable interpretation of "treat" includes eliminating or
ameliorating (improving) any symptom and all symptoms, which are not
described in the Specification. (See Spec. i-f 17.) The broadest reasonable
interpretation of "prevent" includes impeding or preventing all symptoms of
IBD prior to any onset thereof.
Appellants address the claim term "prevent" by arguing that claim 16
does not require prevention, but that "appellants are willing to delete 'to
prevent' from the claim." (Reply Br. 4.) While we agree that practice of
claim 16 does not require "prevention," the scope of claim 16 includes the
prevention ofIBD (see above). As to the apparent proposed amendment to
delete 'to prevent,' that is a matter outside of the PT AB' s jurisdiction.
Unpredictability in the Art
Appellants argue that failure to induce immunotolerance in humans is
not inevitable. (Appeal Br. 3.) In support of that argument, Appellants point
to Feldman for approval of "antigen-specific induction of immunotolerance
for multiple sclerosis," Margalit for oral administration of "a mixture of
8
Appeal2014-008628
Application 13/503,357
autologous collagen extracted proteins to treat IBD," and Trentham, Weiner,
and Fourlanos as "showing successful results in humans in treating
autoimmune diseases." (Id.) Appellants also argue that "[g]eneral
pessimism expressed by the authors of Feldman does not undermine the
holding in In re Brana." (Id. at 4.) Appellants also refer to several
"approved or in phase II trials" listed in Feldman to further argue that
"[g]eneral pessimism expressed by [Feldman] ... cannot take the place of
actual results." (Reply Br. 4.)
The Examiner notes that "[t]olerance-inducing immunotherapy is well
known in the immunological arts," but that results in small animal models
"have not been repeated in human trials." (Ans. 2.) The Examiner points to
Marketletter, Goodnow, and Dong as evidencing the failures or difficulties
in translating animal results to humans, and Pozzilli and Skyler as
evidencing failures in the induction of tolerance to insulin for treatment of
diabetes. (Id. at 2-3.) The Examiner points to Bell as serving "as a clear
demonstration that the induction of immune tolerance is far from predictable
in anything other than carefully chosen in-bred mouse strains." (Id. at 3.)
The Examiner cites Feldman's statements regarding "lack of success of
therapies that interfere with the more complex and flexible features of
antigen-specific adaptive immunity" and the conclusion that "we are
optimistic that eventually, the molecular understanding of tolerance and
immunity will progress, and the 'holy grail' of autoimmunity- long-term
9
Appeal2014-008628
Application 13/503,357
antigen-specific therapy-will be reached." (Id. at 4--5, citing Feldman 612,
right col. and 618, right col.)
Summary
On balance, and considering the above factors, we agree with the
Examiner that undue experimentation would be required to practice the
method of claim 16, particularly given the unpredictability in the art
reflected in the respective articles cited above. While the existence of the
mouse model weighs in favor of enablement, we find it does not favor
enablement to the extent that Appellants argue. Accordingly, we find the
relatively broad scope of claim 16 is not enabled. 6 Moreover, considering
the limited direction or guidance provided in the Specification in light of the
scope of claim 16, we find that Appellants have at most provided an
"invitation to experiment" rather than an enabling disclosure of claim 16.
See Wright, 999 F.2d at 1561.
Conclusion of Law
The preponderance of the evidence of record supports the Examiner's
conclusion that claim 16 fails to satisfy the enablement requirement.
6 We acknowledge the Examiner's statement that the documents relied upon
by Appellants, other than Feldman, "have not been shown to be of record"
and "will not be addressed here." (Ans. 8.) We do not find that statement to
necessarily mean that the documents were not considered, and in any event
they have been addressed herein.
10
Appeal2014-008628
Application 13/503,357
Issue No. 2: Obviousness
Whether a preponderance of the evidence of record supports the
Examiner's conclusion that claim 16 is obvious under 35 U.S.C.
§ 103(a).
Analysis
The Examiner concludes that it would have been prima facie obvious
to one of ordinary skill in the art at the time of the invention to administer
the carbonic anhydrase I (CAI) of Rodriguez to an IBD patient given the
teachings of Rodriguez that CAI can be administered for the treatment of
diseases associated with oxidative stress (FF 3, 4), and Roessner's teaching
that IBD is associated with oxidative stress (FF 5). (Ans. 6.) Furthermore,
according to the Examiner, one of ordinary skill in the art would have been
motivated to perform such a method "as a cheap and convenient therapy for
the disease." (Id. at 6-7.)
We find that the Examiner has satisfied the burden of showing "some
articulated reasoning with some rational underpinning to support the legal
conclusion of obviousness." KSR Int'! Co. v. Teleflex Inc., 550 U.S. 398,
418 (2007). Accordingly, the Examiner has established a prima facie case of
obviousness and, as discussed below, Appellants have not overcome that
prima facie case.
Appellants argue that Rodriguez teaches that "a decrease in carbonic
anhydrase is the cause of oxidative stress," and that administering "carbonic
anhydrase will reduce oxidative stress and therefore treat conditions that are
caused by oxidative stress." (Appeal Br. 4--5.) Furthermore, according to
Appellants, Roessner does not teach that oxidative stress is the cause of IBD,
"but rather that IBD is the cause of oxidative stress." (Id. at 5.) Appellants
11
Appeal2014-008628
Application 13/503,357
thus conclude that "Rodriguez does not teach that carbonic anhydrase l
could be used to treat diseases that are themselves the cause of oxidative
stress," i.e., IBD (id.), but rather teaches "the exact opposite of what the
invention attempts to do - Rodriguez teaches to increase the very causative
agent of the specific autoimmune disease, IBD" (Reply Br. 7).
We are not persuaded by Appellants' arguments. The test for
obviousness is what the combined teachings of Rodriguez and Roessner
would have suggested to one of ordinary skill in the art. See In re Keller,
642 F.2d 413, 425 (CCPA 1981) (citing cases). Moreover, it is well settled
that "the law does not require that the references be combined for the
reasons contemplated by the inventor." In re Beattie, 974 F.2d 1309, 1312
(Fed. Cir. 1992) (citing cases).
Here, Rodriguez teaches the administration of carbonic anhydrase I to
treat or prevent diseases associated with oxidative stress, and provides a
non-exhaustive list of those diseases that includes autoimmune diseases,
such as lupus and multiple sclerosis. (FF 3, 4.) While Rodriquez does not
specifically mention IBD, Roessner states that "[ o ]xidative stress has long
been associated with the pathogenesis of chronic inflammatory bowel
disease (IBD)-related colorectal cancer" (FF 5), and further addresses the
"oxidative stress-driven colorectal carcinoma in IBD." (Roessner 516, left
col.)
We are unpersuaded by Appellants' argument that Rodriguez teaches
that carbonic anhydrase can be used to "treat conditions that are caused by
oxidative stress," and that Roessner teaches that "IBD is the cause of
oxidative stress," but then conclude that the references do not teach or
suggest that carbonic anhydrase can be used to treat IBD. (Appeal Br. 3.)
12
Appeal2014-008628
Application 13/503,357
The distinction Appellants appear to be making between treating IBD and
treating conditions of IBD is not persuasive of nonobviousness. Moreover,
that a person of ordinary skill in the art would have combined the teachings
of Rodriguez and Roessner for a reason different than Appellants is also
unpersuasive of nonobviousness. See Beattie, 974 F.2d at 1312.
Conclusion of Law
A preponderance of the evidence of record supports the Examiner's
conclusion that claim 16 is obvious under 35 U.S.C. § 103(a).
SUMMARY
We affirm the rejections of claim 16.
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
13