Ex Parte Chvatchko et al

Patent Trial and Appeal Board

Sep 28, 2016

10204387 (P.T.A.B. Sep. 28, 2016)

UNITED STA TES p A TENT AND TRADEMARK OFFICE
APPLICATION NO.
10/204,387
7590
David S Resnick
Nixon Peabody,LLP
100 Summer Street
Boston, MA 02110
FILING DATE FIRST NAMED INVENTOR
01/30/2003 Yolande Chvatchko
09/28/2016
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.
057878-000010 1269
EXAMINER
JIANG, DONG
ART UNIT PAPER NUMBER
1646
MAILDATE DELIVERY MODE
09/28/2016 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 YOLANDE CHY ATCHKO,
CHARLES DINARELLO, SANTER VANDEVENTER,
MENACHEM RUBINSTEIN, DANIELA NOVICK,
and SOO-HYUN KIM1
Appeal 2015-002311
Application 10/204,3 87
Technology Center 1600
Before JEFFREY N. FREDMAN, JOHN G. NEW, and
RACHEL H. TOWNSEND, Administrative Patent Judges.
NEW, Administrative Patent Judge.
DECISION ON APPEAL
1 Appellants state the real parties-in-interest are Merck Serono SA and Y eda
Research and Development Company Ltd. App. Br. 3.
Appeal 2015-002311
Application 10/204,3 87
SUMMARY
Appellants file this appeal under 35 U.S.C. § 134(a) from the
Examiner's Non-Final Rejection of claims 62, 79, 82 and 93-962 as
unpatentable under 35 U.S.C. 103(a) as being obvious over the combination
of Nishida et al. (US 2002/0128450 Al, September 12, 2002) ("Nishida")
and Novick et al. (US 6,605,280 Bl, August 12, 2003) ("Novick"). 3
We have jurisdiction under 35 U.S.C. § 6(b).
We AFFIRM.
NATURE OF THE CLAIMED INVENTION
Appellants' invention is directed to the use of inhibitors of IL-18 in
the preparation of a medicament for treatment and/or prevention of liver
injury. Abstract.
REPRESENTATIVE CLAIM
Appellants argue all of the claims together. App. Br. 15. Claim 62 is
representative of the claims on appeal and recites:
62. A method of treating chronic alcoholic hepatitis, the
method comprising administering to a host in need thereof an
effective IL-18 activity inhibiting amount of about 1 to 2 mg/kg
of body weight of an IL-18 binding protein (IL- l 8BP) isoform
selected from IL- l 8BP isoforms a and c, or a mutein of IL- l 8BP
isoform a or c having conservative amino acid substitutions and
2 Claims 1-61, 63-78, 80-81, 83-92, and 97 are canceled. App. Br. 20-21.
3 Claims 62, 79, 82 and 93-96 were also rejected by the Examiner over the
combination of H. Okamura et al., Cloning of a new cytokine that induces
IFN-gamma production by T cells, 378(6552) NATURE 88-91 (1995) and
Novick. See Non-Final Act. 2. The Examiner has withdrawn this rejection.
Ans. 6.
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Application 10/204,3 87
inhibiting IL-18 activity, or a fused protein of IL- l 8BP isofonn
a or c comprising an IgG heavy chain CH2 and CH3 domain and
inhibiting IL-18 activity.
App. Br. 20.
ISSUES AND ANALYSES
We agree with, and adopt, the Examiner's findings and conclusion
that the appealed claims are prima facie obvious over the cited prior art
references. We address the arguments raised by Appellants on appeal
below.
Issue
Appellants argue the Examiner erred because the combined cited prior
art would not provide an artisan of ordinary skill in the art a reasonable
expectation that the claimed method would work. App. Br. 15.
Analysis
Appellants argue that Nishida describes anti-IL-18 antibody fragments
and further describes a list of more than 100 conditions that that these
antibody fragments can be used to treat. App. Br. 15. Appellants contend
that Nishida provides no explicit examples of treating chronic liver disease
and that the Examiner is merely selecting Nishida' s teaching of treating
"viral hepatitis, alcoholic hepatitis, toxic hepatitis, primary biliary cirrhosis,
fulminant hepatitis, viral hepatocirrhosis, alcoholic hepatocirrhosis, toxic
hepatocirrhosis, cholestatic hepatitis, hepatocellular carcinoma, acute
hepatitis, fatty liver, tumors of liver, disorders in hepatic vessels, etc." as
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Application 10/204,3 87
being selected from a "laundry list" of diseases which can be treated with
anti-IL18 antibody fragments. Id. (see Nishida iJ 51).
Appellants also point to evidence which, they argue, demonstrates that
a number of the conditions listed in Nishida cannot be treated by
administration of an IL-18 inhibitor, but may actually be treated by
stimulation ofIL-18 activity (and not by inhibition ofIL-18 activity). App.
Br. 15. Appellants point to Exhibits A-D4 of their Appeal Brief which, they
contend, demonstrate that graft versus host disease, diabetes, pancreatic
cancer, and liver cancer, all of which are included in Nishida's list of
diseases treatable with an IL-18 inhibitor, are in fact treatable with IL-18
itself. Id. at 16. Appellants take the position that if a skilled artisan could
not reasonably expect all the conditions listed by Nishida to be susceptible to
treatment, the artisan could not therefore have reasonably expected treatment
of alcoholic hepatitis and hepatocirrhosis to work. Id. Appellants assert that
the Examiner's findings to the contrary constitute impermissible use of
hindsight analysis.
4 I. Okamoto et al., IL-18 Prevents the Development of Chronic Graft-
Versus-Host Disease in Mice, 165 (11) J. IMMUNOL., 6068-74 (2000)
(Exhibit A); H. Rothe et al., IL-18 Inhibits Diabetes Development in
Nonobese Diabetic Mice by Counterregulation ofThl-Dependent
Destructive Insulitis, 162 (3) J. IMMUNOL., 1230-36 (1999) (exhibit B); A.
Carbono et al., Human Pancreatic Carcinoma Cells Secrete Biooctive
lnterleukin-18 after Treatment with 5-Fluorourocil, 4 (2) CANCER BIOL. &
THERAPY, 231-41 (2005) (Exhibit C); W. Sun et al., Combined gene therapy
for murine liver cancer with interleukin-18 and cytosine deaminase genes,
available at: http://www.ncbi.nlm.nih.gov/pubmed/1l67 6879 (English
translation from 9 (5) ZBONGHUA GAN ZANG BING ZAZHI, 300-02 (2001))
(Exhibit 4).
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Appellants argue further that, whereas the teaching of Nishida does
not establish a motivation to try to treat chronic alcoholic hepatitis with an
IL-18 inhibitor, it certainly cannot establish a motivation to try to treat
chronic alcoholic hepatitis with the specific dosages of the IL- l 8BP-derived
polypeptides recited in the claims. App. Br. 17. Appellants point to the
Federal Circuit Court's decision in Impax Labs., Inc. v. Aventis
Pharmaceuticals Inc., 545 F.3d 1312 (Fed. Cir. 2008), in which our
reviewing court held that, because a prior art patent did not enable one
skilled in the art to arrive at the claimed method without undue
experimentation, the prior art did not anticipate the patent-in-suit. Id. (see
Impax, 545 F.3d at 1316). Appellants contend that, as in Impax, Nishida
provides no disclosure of IL- l 8BP or any other non-antibody IL-18
inhibitor, much less dosage guidelines for such molecules. Id. Similarly,
Appellants assert, Novick provides no guidance regarding dosages for IL-
18BP polypeptides. Therefore, argue Appellants, neither Nishida nor
Novick provide any motivation or suggestion to treat chronic alcoholic
hepatitis with any IL-18 inhibitor, much less with the claimed IL- l 8BP-
derived polypeptides. Id.
The Examiner responds that Nishida is directed to generating a
specific monoclonal antibody to IL-18. Ans. 7. The Examiner points out
that IL-18 was well known in the art at the time the application was filed
(IL-18 was first described in 1989), and that a prior art reference does not
need to reveal all that is known in the art. Id. The Examiner finds, contrary
to Appellants' argument that Nishida's list has no practical nor even
theoretical basis and represents no more than wishful thinking, that although
IL- 18BP was discovered at a later date, the biological activities and clinical
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Appeal 2015-002311
Application 10/204,3 87
significance of IL-18 were well-known in that art to be similar to those of
IL-1, to which IL-18 is related. Id. More particularly, the Examiner finds
Novick teaches the detrimental effect of IL-18 in vivo was first demonstrated
in liver cells. Id. at 8 (citing Novick col. 1, 11. 54-62). Moreover, finds the
Examiner, Novick teaches that IL-18 plays a potential role in
immunoregulation or in inflammation by augmenting the functional activity
of the Fas ligand on Thl cells, and consequently, blocking the biological
activity of IL-18 in human disease is a therapeutic strategy in the treatment
of many diseases. Id. (citing Novick col. 2, 11. 41-43, 49-51).
The Examiner also points to two other prior art applications cited in
the previous Office Action, Ghayer et al. (US 7,767,207 B2, August 3, 2010)
("Ghayer") and Su et al. (US 5,985,863, November 16, 1999) ("Su"). Ans.
8-9. The Examiner finds Ghayer teaches the use of an anti-IL-18 antibody
for treating a human subject suffering from a disorder including, inter alia,
chronic active hepatitis. Id. (citing. e.g., Ghayer col. 14, 11. 4-20, claim 15).
The Examiner finds Su teaches methods for decreasing the production of IL-
18 for treating or reducing the advancement, severity, or effects ofIGIF- or
IFN-y-mediated inflammatory, infectious or autoimmune conditions
including hepatitis. Id. at 9 (citing Su col. 11, 11. 17-19).
Therefore, the Examiner finds, at the time of filing, it was well known
in the art that IL-18 play a role in the development of inflammatory diseases,
including inflammation of the liver (hepatitis) such as chronic alcoholic
hepatitis or alcoholic hepatocirrhosis. Ans. 9. The Examiner consequently
concludes that Appellants' argument that Nishida teaches no practical or
theoretical basis for believing that inhibition of IL-18 is a useful strategy for
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Application 10/204,3 87
treating liver disease, but rather represents no more than "wishful thinking,"
is incorrect. 5 Id.
The Examiner also finds that, with respect to the references presented
as exhibits A-Din Appellants' Brief, none are related to the presently
claimed invention, nor do they successfully discredit the prior art cited by
the Examiner. Ans. 10.
We are not persuaded by Appellants' arguments. As an initial matter,
we are not persuaded by Appellants' reliance upon Impax. The relevant
issue in Impax was whether the prior art reference was enabling for purposes
of anticipating the patent-in-suit under 35 U.S.C. § 102. The claims of the
instant application stand rejected as being obvious over the prior art, and the
proper standard under 35 U.S.C. § 103(a) is not whether a prior art reference
teaches every limitation of the claims at issue, or even whether the prior art
is enabling for purposes of anticipating the claims at issue, but rather "what
the combined teachings of the references would have suggested to those of
ordinary skill in the art." In re Keller, 642 F.2d 413, 425 (C.C.P.A. 1981).
Furthermore, "under§ 103, a reference need not be enabled; it qualifies as
prior art, for whatever is disclosed therein." Amgen, Inc. v. Hoechst Marion
Roussel, Inc., 314 F.3d 1313, 1357 (Fed. Cir. 2003).
5 With respect to these references, Appellants argue that Ghayer and Su, like
Nishida, merely include "laundry lists" of diseases in which they claim IL-
18 plays a role. App. Br. 19. However, Appellants argue, like Nishida,
numerous diseases in each of these references respond to treatment not with
an IL-18 inhibitor, but to treatment with IL-18 itself. Id. Thus, these lists do
not actually represent a teaching of diseases that can be treated with any IL-
18 inhibitor, but rather, mere unsubstantiated and incorrect speculation that
would not serve as motivation to try for one of ordinary skill in the art. Id.
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Appeal 2015-002311
Application 10/204,3 87
More importantly, despite Appellants' argument that the prior art does
not teach the dosages of "about 1 to 2 mg/kg of body weight" recited in
claim 62, "discovery of an optimum value of a result effective variable ... is
ordinarily within the skill of the art." In re Boesch, 617 F.2d 272, 276
(C.C.P.A. 1980). First, paragraph [0054] ofNishida teaches: The present
agent is usually administered, to an adult human patient, in a dose of 1 µg-
1 g/shot, more preferably, about 10 µg-100 mg/shot on the present peptide
basis with a frequency of 1--4 shot/day or 1-5 shot/week over one day to one
year, which falls within the range recited in claim 62. Furthermore, we find
that, given the teachings of the IL-18-related art of the ten years prior to
Appellants' filings, determination of an optimal dosage range would be
within the scope of a person of ordinary skill's knowledge and abilities. For
example, Ghayer explicitly teaches: "[a]n exemplary, non-limiting range for
a therapeutically or prophylactically effective amount of an (anti-human IL-
18) antibody or antibody portion of the invention is 0.1-20 mg/kg, more
preferably 1-10 mg/kg," which overlaps with Appellants' recited range. See
Ghayer col. 18, 11. 41--44. Similarly, Su teaches:
Dosage levels of between about 0.01 and about 100 mg/kg body
weight per day, preferably between about 0.5 and about 75 mg/kg
body weight per day of the ICE inhibitor compounds described
herein are useful in a monotherapy for the prevention and
treatment of IGIF or IFN-y mediated conditions, diseases, or
effects.
Su col. 10, 48-53. For these reasons, we consequently conclude that
determination of the range of dosages recited in claim 62 would have been
within the skill of, and therefore obvious to, one of ordinary skill in the art.
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Application 10/204,3 87
With respect to the main thrust of Appellants' argument that the
teachings of Nishida would not motivate an artisan of ordinary skill to
combine the cited prior art to arrive at Appellants' invention, we are not
persuaded. The Examiner has shown that Nishida, as well as other cited
prior art (e.g., Ghayer and Su) demonstrate that it was known at the time
Appellants' application was filed that IL-18 inhibitors could be effective in
combating inflammatory diseases, and suggested that, inter alia, chronic
diseases of the liver, could be treated with IL-18 inhibiting agents. It is not
necessary, as Appellants suggest, that the prior art explicitly demonstrate
that IL-18 inhibitors would be effective in treating chronic liver disease;
rather, the question is what would the combined prior art have suggested to
an artisan of ordinary skill? Keller, 642 F.2d at 425. We agree with the
Examiner that there are sufficient teachings or suggestions in the prior art
that use of IL-18 inhibitors might be effective in the treatment of chronic
liver disease, including "chronic alcoholic hepatitis," such that an artisan
would be motivated to combine the teachings of Nishida and Novick to
arrive at Appellants' invention. Because the combination of references teach
or suggest the limitations of the claims (which, with the exception of the
recited dosages of claim 62, Appellants do not dispute), we agree that the
Examiner has established a prima facie case of obviousness.
Nor are we persuaded by Appellants' proffer of their Exhibits A-Das
proof that the teachings of Nishida would not be relied upon by a person of
ordinary skill in the art. None of these references are directed to treatment
of a chronic disease of the liver; rather, they are directed generally to the role
of IL-18 in chronic graft-vs-host disease, diabetes, and neoplasms. As such,
they do not outweigh the suggestions of the prior art that IL-18 inhibitors
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Application 10/204,3 87
may be useful in the treatment of chronic alcoholic liver diseases sufficiently
to overcome the Examiner's prima facie conclusion of obviousness.
DECISION
The Examiner's rejection of claims 62, 79, 82 and 93-96 as
unpatentable under 35 U.S.C. § 103(a) is affirmed.
No time period for taking any subsequent action in connection with
this appeal may be extended under 37 C.F.R. § l.136(a)(l). See 37 C.F.R.
§ l.136(a)(l )(iv).
AFFIRMED
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