Ex Parte Medof et al

Patent Trial and Appeal Board

Aug 29, 2016

12514024 (P.T.A.B. Aug. 29, 2016)

UNITED STA TES p A TENT AND TRADEMARK OFFICE
APPLICATION NO. FILING DATE FIRST NAMED INVENTOR
121514,024 0510712009 M. Edward Medof
68705 7590 08/31/2016
TAROLLI, SUNDHEIM, COVELL & TUMMINO, LLP
1300 EAST NINTH STREET
SUITE 1700
CLEVELAND, OH 44114
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.
CWR-8294US PCT 7227
EXAMINER
KANTAMNENI, SHOBHA
ART UNIT PAPER NUMBER
1627
NOTIFICATION DATE DELIVERY MODE
08/31/2016 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):
rkline@tarolli.com
docketing@tarolli.com
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
BEFORE THE PATENT TRIAL AND APPEAL BOARD
Ex parte M. EDWARD MEDOF, FENG LIN, and QING LI 1
Appeal2014-001860
Application 12/514,024
Technology Center 1600
Before DONALD E. ADAMS, FRANCISCO C. PRATS, and
JOHN G. NEW, Administrative Patent Judges.
PRATS, Administrative Patent Judge.
DECISION ON APPEAL
This appeal under 35 U.S.C. § 134(a) involves claims to method of
reducing the symptoms, duration or severity of age-related macular
degeneration. The Examiner rejected the claims for obviousness.
We have jurisdiction under 35 U.S.C. § 6(b). We affirm.
STATEMENT OF THE CASE
The sole rejection before us for review is the Examiner's rejection of
claims 1, 6, 7, 10, 18, and 22-24 as unpatentable under 35 U.S.C. § 103(a)
for obviousness over Kikuchi (U.S. Patent No. 5,238,964 (issued Aug. 24,
1 Appellants state that the "real party in interest is Case W estem Reserve
University." Br. 2.
Appeal2014-001860
Application 12/514,024
1993)) and Krieg (U.S. Patent Appl. Pub. No. 2006/0045880 Al (published
Mar. 2, 2006)). Final Action 4--5; Ans. 3.
Claim 1 is representative and reads as follows:
Claim 1: A method of reducing the symptoms, duration
or severity of age-related macular degeneration (AMD) or
multiple sclerosis in a subject, the method comprising:
administering a therapeutically effective amount of a
pharmaceutical composition to the subject, the pharmaceutical
composition including at least one amidine compound or
pharmaceutical salt thereof having anti-complement activity,
wherein the at least one amidine compound includes the
following general formula (I):
(l.)
wherein Ri and R2 each represent a hydrogen atom, or a
straight or branched chain alkyl group of 1 to 6 carbons;
wherein R3 represents a straight or branched chain alkyl
group of 1 to 6 carbon atoms or a group of the formula R4-B-
(CH2)n- where
n is 1 to 2,
B is -0-or -NH- and
R4 is a hydrogen atom, Rs-CO- or
2
Appeal2014-001860
Application 12/514,024
.
.
\
.o'··•·i:.:1·--. ,,..n;·~ ·'"o:-.-·-.t .. "r·--------- ... :j,:~.:t.\.J
=~/ ·•· .
Rs is a straight or branched chain alkyl group of 1 to 15
carbon atoms; and wherein Ri and R3 taken together via 2 to 4
carbon atoms optionally form a ring containing double bonds
and straight or branched alkyl groups of 1 to 4 carbon atoms as
substituents;
or a pharmaceutically acceptable salt thereof.
Br. 17-18.
In response to a species election requirement, Appellants elected age-
related macular degeneration (AMD) as the treated disease, and the
compound having formula (II) as the administered compound. Final Action
2. Claims 1, 6, 7, 10, 18, and 22-24, therefore, have been examined only to
the extent they read on the elected invention and species. Id.
We, therefore, limit our analysis of claims 1, 6, 7, 10, 18, and 22-24
to the patentability of the elected species, and the extent to which the claims
read on them. See Ex parte Ohs aka, 2 USPQ2d 1460, 1461 (BP AI 1987).
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Appeal2014-001860
Application 12/514,024
OBVIOUSNESS
Appellants do not argue the rejected claims separately. We select
claim 1 as representative of the rejected claims. 37 C.F.R. § 41.37(c)(iv).
The Examiner cited Kikuchi as evidence that the elected compound
(compound of Appellants' formula (II)) was known in the art as a serine
protease inhibitor useful in pharmaceutical compositions for treating
disorders involving serine proteases. Final Action 5. The Examiner found
that Kikuchi differs from claim 1 in that Kikuchi "does not teach a method
of treating age-related macular degeneration comprising administering" a
compound of formula (II). Id.
To address that deficiency, the Examiner cited Krieg as disclosing a
method of treating AMD by administering an inhibitor of apelin activity,
wherein "the inhibitor of apelin activity is a serine protease inhibitor." Id.
Based on the references' teachings, the Examiner concluded that an
ordinary artisan would have considered it obvious to use the compound of
formula (II) to treat AMD, "because Krieg teaches that serine protease
inhibitors can be used in the method of treating age related macular
degeneration." Id. In particular, the Examiner reasoned that, given the
references' teachings, an ordinary artisan "would have been motivated to
administer [the] serine protease inhibitor ... of formula (II) with [a]
reasonable expectation of success [in] treating age-related macular
degeneration." Id.
As stated in In re Oetiker, 977 F.2d 1443, 1445 (Fed. Cir. 1992):
[T]he examiner bears the initial burden . . . of presenting a
prim a facie case of unpatentability ....
After evidence or argument is submitted by the applicant
in response, patentability is determined on the totality of the
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Appeal2014-001860
Application 12/514,024
record, by a preponderance of evidence with due consideration
to persuasiveness of argument.
Appellants' arguments do not persuade us that a preponderance of the
evidence fails to support the Examiner's prima facie case as to representative
claim 1.
Appellants do not dispute the Examiner's finding that Kikuchi
discloses that the elected compound of formula (II) is a serine protease
inhibitor. Rather, Appellants contend that Krieg discloses that the AMD-
treating serine protease inhibitor must inhibit "'a serine protease that cleaves
a polypeptide specifically after an arginine residue.'" Br. 9 (quoting Krieg
i-fi-1 49, 52). Appellants contend that, given the definition of "specific" on
page 1861 of the American Heritage Dictionary, an ordinary artisan would
have understood that Krieg requires "an inhibitor of apelin activity is an
inhibitor of a serine protease that cleaves a polypeptide specifically after an
arginine residue and does not cleave a polypeptide after other amino acid
residues." Br. 10.
Appellants contend that, in contrast to Krieg's alleged requirement for
that specificity of inhibition, Kikuchi describes its serine protease inhibitor
compounds as inhibiting a number of different serine proteases, including
serine proteases that cleave at sequences in addition to the sequence
specified in Krieg. Id. at 10-11 (citing Kikuchi, 6:44--47; Enzo Life
Sciences product sheet for the compound of Appellants' formula (II); B.
Walker and J.P. Lynas, Review, Strategies for the inhibition of serine
proteases, 58 Cell. Mol. Life Sci. 596-624 (2001) (hereinafter "Walker")).
Appellants contend, moreover, that the Examiner has not provided any
evidence suggesting that Kikuchi' s compound of Appellants' formula (II)
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Application 12/514,024
would have the specificity taught in Krieg, nor do Kikuchi and Krieg suggest
that Kikuchi's compound would have that specificity. Br. 10.
In response, the Examiner notes that Kikuchi discloses that its serine
protease inhibitors inhibit trypsin, and also notes that trypsin-like proteases,
as shown by Walker, were known in the art to cleave peptide bonds
following a positively charged amino acid such as lysine or arginine. Ans. 4
(citing Walker, 597). Therefore, the Examiner reasons, an ordinary artisan
would have recognized that Kikuchi' s inhibitors would be capable of
inhibiting serine proteases having the activity taught in Krieg as being
critical to its AMD treatment. Id. at 4--5.
We find that the Examiner has the better position.
Krieg discloses "the use of compositions that affect apelin signaling to
treat patients suffering from various angiogenesis-related and/or apoptosis-
related diseases or conditions." Krieg i-f 4. Krieg explains that apelin is a
"natural ligand" to a receptor, APJ, which is involved in angiogenesis. Id. at
i-f 7. Krieg explains that the apelin polypeptide is initially produced as a
larger polypeptide that is cleaved into smaller polypeptides, including a
"peptide consisting of the C-terminal 13 amino acids of the apelin
polypeptide[, which] is necessary and sufficient for the ability of an apelin
polypeptide to interact with APJ." Id.
Krieg discloses that AMD is among the unregulated angiogenesis-
related disorders that are treatable by administering an inhibitor of apelin
activity. Id. at i-fi-1 6, 52. Krieg discloses that, in one embodiment of its
AMD treatment methods, "the inhibitor of apelin activity is an inhibitor of a
serine protease that cleaves a polypeptide specifically after an arginine
residue." Id. at i-f 52.
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Appeal2014-001860
Application 12/514,024
Although Krieg might not disclose that the elected species of serine
protease inhibitor of formula (II) recited in Appellants' claim 1 was useful in
its AMD treatment methods, Kikuchi undisputedly discloses that the serine
protease inhibitor of formula (II) was known in the art to be useful in
pharmaceutical compositions for treating other serine protease-mediated
disorders. Kikuchi 2:46-48 ("They are agents whose safety, and
effectiveness in treating pancreatitis, are already known."); see also id. at
1: 15-17 (describing use of compound in medicinal compositions for treating
cerebrovascular contraction caused by subarachnoid bleeding). Kikuchi
discloses:
The present compound is a serine protease inhibitor
which can inhibit various kinds of serine protease including
C Ir, C ls, factor B and factor D of complement system, factor
XIIa, factor Xa and thrombin of coagulation system, plasma
kallikrein of quinine system, plasmin of fibrinolytic system,
trypsin, etc. That is, the present compound inhibits
inflammation reactions originating in plasma protein which
advance under the action of said serine proteases.
Id. at 6:44--52.
As the Examiner points out (Ans. 4), and as seen in Walker, it was
known in the art that trypsin-like serine proteases cleave polypeptides after
basic amino acid residues, which undisputedly include arginine. See Walker
597 (describing trypsin-like serine proteases as "cleaving after basic amino
acids").
Thus, in sum, Krieg teaches that inhibitors of serine proteases that
cleave after arginine residues would be useful in its methods of treating
AMD, and Kikuchi discloses that the elected compound of formula (II) was
suitable for use in therapeutic methods involving the inhibition of serine
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Application 12/514,024
proteases having trypsin activity, a cleavage activity that an ordinary artisan
would have understood includes cleaving after arginine residues. Given
these teachings, we agree with the Examiner that an ordinary artisan would
have had sufficient reason for, and a reasonable expectation of success in,
using the compound of formula (II) in Krieg' s AMD treatment methods.
The facts that (a) Krieg describes the target inhibited serine protease
as one that "cleaves a polypeptide specifically after an arginine residue"
(Krieg i-f 52 (emphasis added)), and (b) Kikuchi describes its inhibitor as
inhibiting a variety of serine proteases (Kikuchi 6:44--52), do not persuade
us to the contrary. Clearly critical to Krieg's AMD treatment method is the
inhibition of apelin activity, which is achieved by inhibiting a serine
protease that cleaves after an arginine residue. Krieg i-f 52. As discussed
above, Kikuchi's inhibitor undisputedly possesses that activity. Kikuchi
6:44--52; see also Walker 597 (describing trypsin-like serine proteases as
"cleaving after basic amino acids").
Thus, that Kikuchi' s inhibitor might inhibit enzymes in addition to
Krieg's target enzyme does not negate the fact that an ordinary artisan would
have recognized that Kikuchi's inhibitor meets Krieg's critical criterion of
inhibiting a serine protease that cleaves after arginine residues. Moreover,
other than Krieg's use of the term "specifically" to describe the target
enzyme that must be inhibited, Appellants direct us to no teaching in Krieg,
or Kikuchi, suggesting that inhibition of serine proteases in addition to
Krieg's target enzyme would render a candidate serine protease inhibitor
unsuitable for use in Krieg' s AMD treatment methods.
We acknowledge also, but are unpersuaded by, Appellants' arguments
(Br. 12-15), that because of the unpredictability in the art, an ordinary
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Application 12/514,024
artisan would not have had a reasonable expectation that Kikuchi' s inhibitor
would reduce the duration, symptoms, or severity of AMD. It may be true
that over 26,000 serine proteases "were known and implicated in diverse
biological processes." Br. 13 (citing (M. J. Page and E. Di Cera, Review,
Serine peptidases: Classification, structure and function, 65 Cell. Mol. Life
Sci. 1220-1236 (2008)).
That many serine proteases were known, however, does not negate the
facts, discussed above, that Krieg identified, as a target for inhibition in its
AMD treatment methods, a serine protease having a particular activity-
cleavage after an arginine residue-and that Kikuchi describes, as useful in
pharmaceutical formulations, a compound capable of inhibiting enzymes
undisputedly known to have that activity. Indeed, Kikuchi's disclosure that
its compound was suitable for use in pharmaceutical compositions (Kikuchi
1: 15-17, 2 :46-48) suggests that concerns regarding a potential lack of
specificity or resulting undesirable side effects would be addressed by using
Kikuchi's compound in Krieg's AMD treatment methods. See Br. 13 (citing
Walker, generally); see also id. at 15 ("For example, without knowing the
specificity of the inhibitors, one skilled in the art could not easily predict
whether a serine protease inhibitor could cause severe side [effects] and thus
be ineffective in treating a disease in a subject.").
As to Appellants' contention that "no specific [AMD] therapy was
known at the time of filing that could either reverse retinal changes or
prevent further progression to complete blindness" (Br. 13 (citing Spec.
i-f 6)), we note that claim 1 requires only "reducing the symptoms, duration
or severity of' AMD (Br. 17), and Appellants do not advance persuasive
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Application 12/514,024
argument or evidence suggesting that the AMD treatment methods suggested
by Krieg and Kikuchi would fail to achieve the results required by claim 1.
Appellants' arguments (App. Br. 14--15) do not persuade us that the
lack of disclosure in the references as to the absolute specificity of Kikuchi' s
compound in relation to apelin inhibition demonstrates that an ordinary
artisan lacked sufficient guidance as to whether Kikuchi' s inhibitor would
function successfully in Krieg's AMD treatment methods.
It is well-settled that "[ o ]bviousness does not require absolute
predictability of success .... For obviousness under§ 103, all that is
required is a reasonable expectation of success." In re Kubin, 561 F.3d
1351, 1360 (Fed. Cir. 2009) (quoting In re O'Farrell, 853 F.2d 894, 903---04
(Fed. Cir. 1988) (emphasis removed).
As the Federal Circuit explained in Kubin, one circumstance in which
the prior art fails to provide a reasonable expectation of success is where the
art suggests "vary[ing] all parameters or try[ing] each of numerous possible
choices until one possibly arrived at a successful result, where the prior art
gave either no indication of which parameters were critical or no direction as
to which of many possible choices is likely to be successful." Id. at 1359
(quoting O'Farrell, 853 F.2d at 903).
Another circumstance in which the prior art fails to provide a
reasonable expectation of success is where the art suggests exploring a
"general approach that seemed to be a promising field of experimentation,
where the prior art gave only general guidance as to the particular form of
the claimed invention or how to achieve it." Id.
In the instant case, as discussed above, Krieg identified, as the target
for inhibition in its AMD treatment methods, a serine protease having a
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Application 12/514,024
particular activity---cleavage after an arginine residue. Because Krieg
identified the particular enzymatic activity that required inhibition in its
AMD treatment methods, we are not persuaded that an ordinary artisan was
faced with either an excessive number of potential inhibitors, or an
over-generalized approach that lacked adequate guidance. Rather, the
ordinary artisan knew which serine protease inhibitors would be suitable for
treating AMD according to Krieg's methods. Moreover, because Kikuchi
describes, as useful in pharmaceutical formulations for treating serine
protease-mediated disorders, a compound capable of inhibiting serine
proteases known to have the activity identified in Krieg as requiring
inhibition, we are not persuaded that an ordinary artisan lacked a reasonable
expectation that Kikuchi's compounds would be useful in Krieg's AMD
treatment.
Accordingly, because Appellants' arguments, for the reasons
discussed, do not persuade us that a preponderance of the evidence fails to
support the Examiner's prima facie case of obviousness as to representative
claim 1, and because Appellants do not advance secondary evidence of
nonobviousness, we affirm the Examiner's rejection of claim 1 over Kikuchi
and Krieg under 35 U.S.C. § 103(a). Because they were not argued
separately, the remaining rejected claims fall with claim 1. 37 C.F.R.
§ 41.37(c)(iv).
SUMMARY
For the reasons discussed, we affirm the Examiner's rejection of
claims 1, 6, 7, 10, 18, and 22-24 under 35 U.S.C. § 103(a) for obviousness
over Kikuchi and Krieg.
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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
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