Ex Parte Benedict

Board of Patent Appeals and Interferences

Jun 2, 2010

10916108 (B.P.A.I. Jun. 2, 2010)

UNITED STATES PATENT AND TRADEMARK OFFICE
__________

BEFORE THE BOARD OF PATENT APPEALS
AND INTERFERENCES
__________

Ex parte JAMES J. BENEDICT
__________

Appeal 2009-012325
Application 10/916,108
Technology Center 1600
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Decided: June 2, 2010
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Before TONI R. SCHEINER, LORA M. GREEN, and
JEFFREY N. FREDMAN, Administrative Patent Judges.

GREEN, Administrative Patent Judge.

DECISION ON APPEAL
This is a decision on appeal under 35 U.S.C. § 134 from the
Examiner’s rejection of claims 7-16. We have jurisdiction under 35 U.S.C.
§ 6(b).

Appeal 2009-012325
Application 10/916,108

STATEMENT OF THE CASE
Claim 7 is representative of the claims on appeal, and reads as
follows:
7. A method of inhibiting the formation of hyaluronic acid-induced
osteophytes in a joint of a mammal, comprising:
(i) providing a composition, comprising a superoxide dismutase
mimic (SODm) associated with a hyaluronic acid (HA) compound, wherein
the composition is a liquid at about 37ºC; and,
(ii) injecting the composition into or close to the joint, wherein the
formation of osteophytes induced by the composition is less than the
formation of osteophytes induced by the HA compound.

The following grounds of rejection are before us for review:
Claims 7-16 stand rejected under 35 U.S.C. § 103(a) as being
rendered obvious by the combination of Ornberg,1 Sakurai,2 and Udipi.3
(Ans. 3.) As Appellant does not separately argue claims 8-13 and 16 from
claim 7, those claims stand or fall with claim 7. 37 C.F.R. § 41.37(c)(1)(vii).
We affirm-in-part.

ISSUE
Has the Examiner established, by a preponderance of the evidence,
that the combination of Ornberg, Sakurai, and Udipi renders the method of
claim 7 obvious?

1 Ornberg, WO 00/72893 A2, published Dec. 7, 2000.
2 Sakurai et al, Anti-inflammatory activity of superoxide dismutase
conjugated with sodium hyaluronate, 14 GLYCOCONJUGATE JOURNAL 723-
728 (1997).
3 Udipi et al., Modification of inflammatory response to implanted
biomedical materials in vivo by surface bound superoxide dismutase mimics,
51 J. BIOMED. MATERIAL RESEARCH 549-560 (2000).
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FINDINGS OF FACT
FF1 According to the Specification:
A number of human and animal diseases have as
symptoms pain and inflammation of the joints. One such
disease is rheumatoid arthritis, a common human autoimmune
disease characterized by chronic inflammation of the synovial
joints (such as the knee) and by subsequent progressive
destruction of articular tissue. A second such disease is
osteoarthritis, which has similar symptoms. One component of
the synovial joints that is degraded in both rheumatoid arthritis
and osteoarthritis is hyaluronic acid (HA).

(Spec. 1.)
FF2 The Specification teaches further that “in osteoarthritis and
rheumatoid arthritis, the concentration and molecular weight of HA in the
joint fluid are reduced by mechanisms attributed, at least in part, to attack on
HA by reactive oxygen species such as superoxide (O2) found in inflamed
joints.” (Id. at 2.)
FF3 The Specification teaches further that based on the above:
[S]everal attempts have been made to treat rheumatoid arthritis,
osteoarthritis, and similar diseases by administering hyaluronic
acid to supplement the degraded or damaged HA in the arthritic
joint. HA has been administered to patients in Europe since
1987. In the United States, three approved commercially
available products are known (Synvisc by Biomatrix/Genzyme,
Hyalgan by Fidia, and Supartz by Seikagaku). HA is usually
injected into the knee or other joint to act as a viscosupplement.
However, these treatments have a disadvantage in that the half-
life of hyaluronic acid in the joint (which typically contains
superoxides that can cleave the HA molecule), based on rabbit
studies with labeled HA, is in the range of about 10-13 hr;
therefore, repeat or supplemental injections of HA are required
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to replace injected HA that is degraded or cleared by
physiological processes or reactive oxygen species.

(Id. at 2 (references omitted).)

FF4 The Specification teaches further that because “superoxides are
believed to play a role in perpetuating the chronic inflammatory state
associated with rheumatoid arthritis . . . . there have been several attempts to
treat rheumatoid arthritis, osteoarthritis, and similar diseases by
administering superoxide dismutase (SOD), an enzyme which catalyzes the
dismutation of superoxide.” (Id. at 2-3.)
FF5 The Specification teaches, however:
One such product, Orgotein®, a bovine SOD with a
Cu/Zn catalytic site, was used in preliminary clinical trials in
patients with inflammatory disorders including rheumatoid
arthritis and osteoarthritis. In patients with active classical
rheumatoid arthritis, intraarticular injection of Orgotein®
ameliorated a number of symptoms, as evidenced by improved
rheumatoid arthritis activity index (morning stiffness, flexion
range, pain, walking time), decrease in the level of rheumatoid
factor, reduced intake of rescue acetaminophen, and overall
improvement in physician and patient global ratings. Similar
benefits were seen in patients with osteoarthritis. However,
Orgotein® was removed from the market because of the
development of immune responses against the bovine enzyme.
Use of SOD is also complicated by solution instability, bell-
shaped dose response curves, high susceptibility to proteolytic
digestion, and limited cell and organ penetration.

(Id. at 3 (references omitted).)
FF6 The Specification teaches that the “present invention relates to a
method of treating pain or inflammation in a joint of a mammal, comprising
(i) providing a composition, comprising a superoxide dismutase mimic
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(SODm) associated with hyaluronic acid (HA), wherein the composition is a
liquid at about 37ºC and (ii) delivering the composition into or close to the
joint.” (Id. at 4.)
FF7 The Specification teaches further that “[i]n another embodiment, the
present invention relates to a method of preventing or suppressing
osteophyte formation in an inflamed joint of a mammal,” the method
comprising “(i) providing a liquid composition comprising a SODm
associated with hyaluronic acid [(HA)] and (ii) delivering the composition to
a joint of a mammal.” (Id.)
FF8 The Examiner rejects claims 7-16 as being rendered obvious by the
combination of Ornberg, Sakurai and Udipi. (See Ans. 3-4 for the statement
of the rejection.) We adopt the Examiner’s findings of fact, and make
additional findings below.
FF9 Sakurai conjugated SOD from bovine erythrocytes with HA.
(Sakurai, Abstract.) Sakurai found:
HA-SOD conjugate exhibited a much higher therapeutic
activity than unconjugated SOD in experimental models of
inflammatory disease. In contrast, SOD or HA alone, or the
mixture of SOD and HA was not as effective as HA-SOD
conjugates.

(Id. at paragraph bridging pp. 726-727.)
FF10 Specifically, according to Sakurai, the conjugate “exhibited much
higher anti-inflammatory activities than HA or SOD in models of
inflammatory diseases such as ischemic oedema of the foot-pad in mice,
carrageenin-induced pleurisy and adjuvant arthritis in rats.” (Id. at
Abstract.)
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FF11 Ornberg teaches that superoxide dismutase catalyzes the reaction that
removes superoxide anions. (Ornberg, 8.)
FF12 Ornberg teaches that “[s]everal non-proteinaceous catalysts which
mimic this superoxide dismutating activity have been discovered.” (Id.)
According to Ornberg, “[t]hese mimics of superoxide dismutase have been
shown to have a variety of therapeutic effects, including anti-inflammatory
activity.” (Id.) The non-proteinaceous mimics comprise an organic ligand
and a transition metal cation. (Id. at 10.)
FF13 The invention of Ornberg relates to the discovery “that the
modification of biomaterials with non-proteinaceous catalysts for the
dismutation of superoxide greatly improves the biomaterial’s resistance to
degradation and reduces the inflammatory response.” (Id. at 9.)
FF14 Ornberg also discloses the conjugation of a SODm with HA. (Id. at
101, Example 15.)

PRINCIPLES OF LAW
The question of obviousness is resolved on the basis of underlying
factual determinations including: (1) the scope and content of the prior art;
(2) the level of ordinary skill in the art; (3) the differences between the
claimed invention and the prior art; and (4) secondary considerations of
nonobviousness, if any. Graham v. John Deere Co., 383 U.S. 1, 17 (1966).
The Supreme Court has recently emphasized that “the [obviousness] analysis
need not seek out precise teachings directed to the specific subject matter of
the challenged claim, for a court can take account of the inferences and
creative steps that a person of ordinary skill in the art would employ.” KSR
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Int’l Co. v. Teleflex Inc., 550 U.S. 398, 418 (2007); see also id. at 421 (“A
person of ordinary skill is also a person of ordinary creativity, not an
automaton.”). “The combination of familiar elements according to known
methods is likely to be obvious when it does no more than yield predictable
results.” Id. at 416. Moreover, an “[e]xpress suggestion to substitute one
equivalent for another need not be present to render such substitution
obvious.” In re Fout, 675 F.2d 297, 301 (CCPA 1982). Moreover, the
Examiner must consider all of the claim limitations in setting forth a
rejection over the prior art. See, e.g., In re Geerdes, 491 F.2d 1260, 1262-63
(CCPA 1974) (in considering grounds of rejection, “every limitation in the
claim must be given effect rather than considering one in isolation from the
others.”).
Moreover, “[i]t is a general rule that merely discovering and claiming
a new benefit of an old process cannot render the process again patentable.”
In re Woodruff, 919 F.2d 1575, 1578 (Fed. Cir. 1990).
As to analogous art:
“A reference is reasonably pertinent if, even though it may be in
a different field from that of the inventor’s endeavor, it is one
which, because of the matter with which it deals, logically
would have commended itself to an inventor’s attention in
considering his problem.” In re Clay, 966 F.2d 656, 659
(Fed.Cir.1992). In other words, “familiar items may have
obvious uses beyond their primary purposes.” KSR Int’l Co. v.
Teleflex, Inc., 550 U.S. 398, [402], 127 S.Ct. 1727, 1742 . . .
(2007).

In re ICON Health and Fitness, Inc., 496 F.3d 1374, 1379-80 (Fed. Cir.
2007) (a reference describing a folding bed found pertinent to appellant’s
folding treadmill).
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ANALYSIS
Appellant argues that the ordinary artisan would not have combined
the references as suggested by the Examiner, as “Ornberg and Udipi deal
with implanted products which are surface conjugated with SODm,” whereas
“Sakurai deals with conjugates of HA and SOD.” (App. Br. 5.) Moreover,
Appellant asserts, “Sakurai is directed to solving the problem of
inflammation induced by ischemia, carageenin-induced pleurisy, or
bacterium-induced (adjuvant) arthritis.” (Id. at 6.) The inflammation
introduced by the implants of Ornberg and Udipi, Appellant argues, may
“follow a different process and lead to different results than the
inflammation induced in the experiments of Sakurai.” (Id. at 6-7.) Thus,
Appellant asserts, the references are not properly combinable. (Id. at 7.)
Appellant argues further that even if the references were properly
combined, the combination would not teach the claimed method. (Id.)
Specifically, Appellant argues, Sakurai focuses on inflammatory ailments,
such as adjuvant arthritis, which is a model for rheumatoid arthritis. (Id.)
According to Appellant, “rheumatoid arthritis is an autoimmune condition
characterized by joint inflammation, bone resorption, and bony erosions,”
and bone resorption and bony erosions “are the opposite of bone growth.”
According to Appellant, the “production of bone in the joints of a
rheumatoid arthritis patient almost only occurs if osteoarthritis is also
present.” (Id.) Appellant argues that “osteoarthritis is a condition brought
about by wear and tear and is characterized by joint space narrowing,
subchonal sclerosis, and osteophytosis,” and the present Specification
“reports an experiment performed on an animal model of osteoarthritis.”
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(Id. at 7-8.) Therefore, Appellant asserts, even if the ordinary artisan used a
SODm as taught by Ornberg or Udipi for SOD in the HA-SOD conjugate of
Sakurai, the ordinary artisan would not expect any reduction in osteophyte
formation as rheumatoid arthritis involves bone loss. (Id. at 8.)
Appellant’s arguments have been considered, but are not found to be
convincing. We agree that Sakurai deals with conjugates of HA and SOD.
But as noted in the Specification, the use SOD in vivo is known in the art to
have problems, such as instability and development of an immune response.
Ornberg teaches that SOD mimics catalyze the same reaction as SOD, are
known to reduce inflammation, and may be used in vivo as demonstrated by
their use to modify biomaterials. In addition, Ornberg specifically teaches
the synthesis of an HA and a SODm conjugate. Thus, we agree with the
Examiner that it would have been obvious to the ordinary artisan to
conjugate HA to a SODm for injection into a joint as taught by Sakurai, such
as in the treatment of rheumatoid arthritis.
We have considered Appellant’s argument that the ordinary artisan
would not have combined Sakurai with Ornberg and Udipi. However,
Sakurai teaches the use of an HA-SOD conjugate, and Ornberg and Udipi
both teach that SOD mimics catalyze the same reaction as SOD, and that
they are also known to reduce inflammation. Thus, the ordinary artisan
would have considered the references to all be reasonably pertinent to one
another.
As to Appellant’s argument that the references as combined do not
specifically teach that a HA-SODm conjugate may be used to inhibit the
formation of hyaluronic acid-induced osteophytes in a joint of a mammal,
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first, the combination does specifically suggest the use of such a conjugate in
the treatment of rheumatoid arthritis, as Sakurai teaches that the conjugate
has anti-inflammatory activity in adjuvant arthritis in rats, a known animal
model for rheumatoid arthritis. Thus, once the conjugate was injected into
or close to a joint, it would inherently inhibit the formation of hyaluronic
acid-induced osteophytes in a joint of a mammal. Second, as noted by the
Specification, HA has been used in the treatment of osteoarthritis, and there
have also been attempts at treating osteoarthritis with SOD. As Sakurai
teaches the use of the HA-SODm conjugate in the treatment of inflammatory
disease generally, and teaches that it exhibited much higher anti-
inflammatory activities than HA or SOD in models of inflammatory diseases
such as ischemic oedema of the foot-pad in mice, carageenin-induced
pleurisy and adjuvant arthritis in rats, it would have been obvious to use the
conjugate in the treatment of osteoarthritis, which is also characterized by
chronic inflammation. (See FF1.) As Appellant notes that osteoarthritis is
characterized by osteophytosis, administration of the HA-SODm conjugate
to a patient with osteoarthritis would again inherently inhibit the formation
of hyaluronic acid-induced osteophytes in a joint of a mammal.
Appellant asserts further that although superoxide dismutase enzymes
and SODms may contain the same elements, their molecular structures are
not the same, and thus it would be unpredictable to extrapolate from the
enzyme to a mimic, and the ordinary artisan would not have a reasonable
expectation of success in using the mimic for the enzyme. (App. Br. 5-6.)
Sakurai teaches the use of a HA-SOD conjugate for the reduction of
inflammation. Ornberg teaches that SOD mimics catalyze the same reaction
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as SOD, and have anti-inflammatory activity in vivo. Thus, we agree with
the Examiner that the ordinary artisan would have had a reasonable
expectation that an HA-SODm conjugate would also have anti-inflammatory
activity. Note that all that is required is a reasonable expectation of success,
not absolute predictability of success. In re O’Farrell, 853 F.2d 894, 903-
904 (Fed. Cir. 1988).
As to the rejection of claims 14-16, Appellant reiterates the arguments
made with respect to claim 7. (App. Br. 9.) Appellant asserts that these
claims are drawn to the use of specific pentamine macrocyclic Mn-SODms
as the SOD mimic. (Id.) According to Appellant, Sakurai teaches the use of
bovine Cu/Zn SOD or E. Coli Mn-SOD, and the active site of the E. Coli
Mn-SOD is very different from the claimed pentamine macrocyclic Mn-
SODm. (Id.) Thus, Appellant argues, it would be unpredictable whether the
specific SODm of claims 14-16 “would have a comparable effect as a SOD
in the work reported by Sakurai.” (Id.)
As Examiner has not made any findings that the prior art teaches the
specific SODm required by claims 14 and 15, we are compelled to reverse
the rejection as to those claims. Claim 16, however, depends from claim 7,
and states that “the dose of SODm is from about 0.01 mg SODm/kg body
weight to about 10 mg SODm/kg body weight.” As Appellant has not
presented any argument as to how that dependent claim is separately
patentable from claim 7, it stands or falls with claim 7. We thus affirm the
rejection as to claim 16.

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CONCLUSION OF LAW
We conclude that the Examiner established, by a preponderance of the
evidence, that the combination of Ornberg, Sakurai, and Udipi renders the
method of claim 7 obvious.
We thus affirm the rejection of claim 7 under 35 U.S.C. § 103(a) as
being rendered obvious by the combination of Ornberg, Sakurai, and Udipi.
As Appellant does not separately argue claims 8-13 and 16 from claim 7,
those claims stand or fall with claim 7, and we affirm the rejection as to
those claims as well.
As the Examiner has not established a prima facie case that the
method of claims 14 and 15, requiring a specific superoxide dismutase
mimic, and rendered obvious by the combination of Ornberg, Sakurai, and
Udipi, we are compelled to reverse the rejection as to those claims.

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-IN-PART

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