David Bar-Or

Patent Trials and Appeals Board

Jul 29, 2019

13227098 - (D) (P.T.A.B. Jul. 29, 2019)

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.
13/227,098 09/07/2011 David Bar-Or 6134-109 4847
22442 7590 07/29/2019
Sheridan Ross PC
1560 Broadway
Suite 1200
Denver, CO 80202
EXAMINER
REYNOLDS, FRED H
ART UNIT PAPER NUMBER
1654
NOTIFICATION DATE DELIVERY MODE
07/29/2019 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):
e-docket@sheridanross.com
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
________________

BEFORE THE PATENT TRIAL AND APPEAL BOARD
________________

Ex parte DAVID BAR-OR1
________________

Appeal 2018-004835
Application 13/227,098
Technology Center 1600
________________

Before JEFFREY N. FREDMAN, JOHN G. NEW, and JAMIE T. WISZ,
Administrative Patent Judges.

NEW, Administrative Patent Judge.

DECISION ON APPEAL

1 Appellant identifies Ampio Pharmaceuticals, Inc. as the real party-in-
interest. App. Br. 3.
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SUMMARY
Appellant files this appeal under 35 U.S.C. § 134(a) from the
Examiner’s Final Rejection of claims 1, 3, 28, 29, and 45.2 Specifically,
claims 1, 3, 28, 29, and 45 stand rejected as unpatentable under 35 U.S.C.
§ 103(a) as being obvious over the combination of D.M. Brown et al., Anti-
VEGF Agents in the Treatment of Neovascular Age-related Macular
Degeneration: Applying Clinical Trial Results to the Treatment of Everyday
Patients, 144(4) AM. J. OPTHALMOL. 627–39 (2007) (“Brown”), Y.-G. He et
al., Evidence for a Role of Platelet-Activating Factor (PAF) in the
Pathogenesis of Age-Related Macular Degeneration (AMD), 48 INVEST.
OPHTHAL. VIS. SCI. (2007), abstract 2200) (“He”), and Bar-Or et al. (US
6,555,543 B2, April 29, 2003) (“Bar-Or ’543”).
Claims 1 and 3 stand rejected as unpatentable under 35 U.S.C.
§ 103(a) as being obvious over the combination of Bar-Or ’543 and T.
Yasukawa, Inflammation in Age-Related Macular Degeneration:
Pathological or Physiological?, 4(2) EXPERT. REV. OPTHALMOL. 107–112
(2009) (“Yasukawa”).
Claims 1 and 3 also stand rejected as unpatentable under 35 U.S.C.
§ 103(a) as being obvious over the combination of Bar-Or et al. (US
2013/0345238 A1, December 26, 2013) (“Bar-Or ’238”) and Yasukawa.
Claims 1 and 3 are further rejected as unpatentable under 35 U.S.C.
§ 103(a) as being obvious over the combination of Bar-Or et al. (US
2016/0015705 A1, January 21, 2016) (“Bar-Or ’705”) and Yasukawa.

2 Claims 46 and 47, although listed in Appellant’s Claim Appendix, have
been withdrawn due to an election/restriction requirement. Final Act. 2.
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Claims 1 and 3 are rejected as unpatentable under the nonstatutory
doctrine of double patenting as being unpatentable over claim 41 of
copending Bar-Or ’238 and Yasukawa.
Claims 1 and 3 stand rejected as unpatentable under the nonstatutory
doctrine of obviousness-type double patenting over claims 8, 11, and 13 of
Bar-Or ’543 and Yasukawa.
Claims 1, 3, and 45 stand rejected as unpatentable under the
nonstatutory doctrine of obviousness-type double patenting over claim 102
of copending Bar-Or ’705 and Yasukawa.
Claims 1 and 3 stand rejected as unpatentable under the nonstatutory
doctrine of obviousness-type double patenting over claim 1 of Bar-Or (US
8,507,496 B2, August 13, 2013) (“Bar-Or ’496”) and G.L. Nicolson,
Metabolic Syndrome and Mitochondrial Function: Molecular Replacement
and Antioxidant Supplements to Prevent Membrane Peroxidation and
Restore Mitochondrial Function, 100 J. CELL. BIOCHEM. 1352–369 (2007)
(“Nicolson”).
Claims 1, 3, 29, and 45 stand provisionally rejected as unpatentable
under the nonstatutory doctrine of obviousness-type double patenting as
being obvious over claims 1, 2, and 4 of copending US Ser. No. 15/387,218
(the “’218 application”) and He.
We have jurisdiction under 35 U.S.C. § 6(b).
We AFFIRM.

NATURE OF THE CLAIMED INVENTION
Appellant’s claimed invention is directed to a method of inhibiting
vascular hyperpermeability comprising administering an effective amount of
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a diketopiperazine, a prodrug of a diketopiperazine or a pharmaceutically-
acceptable salt of either of them to the animal, wherein the diketopiperazine
has the formula set forth in the Specification. Abstr.

REPRESENTATIVE CLAIM
Claim 1 is representative of the claims on appeal and recites:
1. A method of inhibiting vascular hyperpermeability in an
animal having diabetic macular edema or age-related macular
degeneration mediated by vascular hyperpermeability
comprising administering to the animal an effective amount of
an active ingredient, wherein the active ingredient comprises a
diketopiperazine, a prodrug of a diketopiperazine or a
pharmaceutically-acceptable salt of either of them, wherein the
diketopiperazine is selected from the group consisting of aspartic
acid-alanine DKP (DA-DKP), methionine-arginine (MR-DKP)
and tyrosine-glutamic acid DKP (YE-DKP).

App. Br. 27.

ISSUES AND ANALYSES
We adopt the Examiner’s findings, reasoning, and conclusion that the
claims on appeal are prima facie obvious over the cited prior art. We
address the arguments raised by Appellant below.

A. Rejection of claim 1, 3, 28, 29, and 45 over Brown, He, and Bar-Or
’543

Issue
Appellant argues that the Examiner erred because: (1) a person of
ordinary skill would not have been motivated to combine the references; (2)
the He reference neither teaches nor suggests that platelet activating factor
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(“PAF”) is a target in intervention; (3) Vascular endothelial growth factor
(“VEGF”) expression is controlled at many levels; (4) the rejection is based
on hindsight reasoning; and (5) Appellant’s alleged unexpected result that
there is an additional mode of action of the claimed method. App. Br. 5.

Analysis
The Examiner finds that Brown teaches that clinical trials have
demonstrated that the use of anti-VEGF agents to treat neovascular age-
related macular degeneration have demonstrated positive results. Final Act.
3 (citing Brown title, 628, table). The Examiner finds that Brown teaches
that no other treatments are as effective as anti-VEGF agents, which provide
a rapid improvement in visual acuity. Id. (citing Brown 631).
The Examiner finds that He teaches the role of platelet-activating
factor (“PAF”) in the context of age-related macular degeneration. Final
Act. 3. The Examiner finds that, in the context of exudative age-related
macular degeneration, VEGF production is promoted by PAF, and
antagonists to that protein reduced VEGF production. Id. (citing He ¶¶ 1, 3).
The Examiner finds that He demonstrates that PAF is metabolically
upstream from VEGF in the relevant biochemical pathway, and that
reduction of platelet activating factor reduces VEGF and ameliorates
macular degeneration. Id.
The Examiner finds that Bar-Or ’543 teaches the use of
diketopiperazines to inhibit PAF. Final Act. 3 (citing Bar-Or Abstr.).
Specifically, the Examiner finds that Bar-Or ’543 teaches that the cyclic
dipeptide Asp-Ala inhibits the effects of PAF by binding to both PAF and its
receptors. Id. (citing Bar-Or ’543 col. 3, ll. 31–34). The Examiner finds that
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such inhibition of PAF can be used to treat disorders mediated by PAF in
humans. Id. at 3–4 (citing Bar-Or ’543 col. 6, l. 16–18, 22).
The Examiner concludes that it would therefore have been obvious to
a person of ordinary skill to inhibit PAF by using the diketopiperizines of
Bar-Or ’543 to reduce the levels of VEGF in exudate age related macular
degeneration, as taught by He and Brown, the latter demonstrating that
VEGF inhibition is an effective treatment for that disorder. Final Act. 4.
The Examiner further concludes that, because He teaches that inhibition of
PAF will reduce levels of VEGF, a skilled artisan would have a reasonable
expectation of success in combining the references to treat age-related
macular degeneration. Id.
Appellant argues that the Examiner’s prima facie case fails to provide
the requisite motivation to combine the references to arrive at the claimed
invention. App. Br. 8. Appellant contends that Brown teaches that VEGF is
a vascular endothelial cell-specific growth factor and is a potent promoter of
angiogenesis and inducer of vascular permeability, and that VEGF inhibitors
are well known in the art for the treatment of age-related macular edema. Id.
Appellant contends that the combination of references proposed by the
Examiner concludes that a skilled person, presumably as an alternative
treatment to the known successful treatment of VEGF inhibitors, would
combine He, which teaches that PAF may have a role in the early
pathogenesis of exudative age-relate macular degeneration, with a known
inhibitor of PAF, as taught by Bar-Or ’543. Id.
Appellant asserts that a person of ordinary skill in the art would not
have been motivated to try using DA-DKP from Bar-Or ’543 to inhibit PAF
with the ultimate goal of inhibiting the activity of VEGF. App. Br. 9.
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Appellant argues that VEGF is recognized as a successful target for
therapeutic intervention, and that there are known therapeutics to
successfully inhibit VEGF activity. Id. Therefore, contends Appellant,
there is no reason a skilled artisan would seek a therapeutic intervention to
indirectly inhibit VEGF, because direct inhibition of VEGF was known to be
successful at treating age-related macular degeneration. Id.
Furthermore, Appellant argues, He only suggests a role for PAF in the
pathophysiology of AMD and does not teach that PAF is an important or
even useful target for therapeutic intervention in treatment of age-related
macular degeneration. App. Br. 9. According to Appellant, He teaches only
that a PAF receptor agonist and antagonist can modulate VEGF production,
without any demonstration that direct regulation of PAF would have the
same effect. Id.
However, Appellant argues, it was known in the art that VEGF
expression is controlled at many levels including transcription, mRNA
stability through the binding of regulatory protein to the 3ʹ untranslated
region and mRNA translation via IRES sequences present in the 5ʹ
untranslated region, and is thus regulated by a plethora of external factors.
App. Br. 9 (citing G. Pages et al., Transcriptional Regulation of the
Vascular Endothelial Growth Factor Gene–a Concert of Activating Factors,
65 CARDIOVASCULAR RES. 564, 565 (2005)). Appellant asserts that, based
upon this knowledge, a skilled artisan would be discouraged from trying to
inhibit VEGF activity by controlling one single upstream factor (i.e., PAF)
when there can be multiple other factors that affect VEGF activity, and
particularly when there exist multiple known successful therapies directly
affecting VEGF. Id. Consequently, Appellant argues, a person of ordinary
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skill would not have and any motivation to combine the references, and
Appellant alleges that the combination is based on the use of the present
claims in an impermissible hindsight analysis to piece together a rationale
for the combination. Id.
Appellant argues further that, in contrast to the Examiner’s purported
reason for use of a DKP in the claimed methods based on its activity as a
PAF inhibitor, the present claims are based upon the inventor’s allegedly
surprising discovery that DA-DKP has an activity that is independent of
VEGF activity and is also effective in the treatment of endothelial cells to
inhibit vascular permeability. App. Br. 10. Appellant points to Examples 1
and 2 of the Specification, which demonstrate that DA-DKP has the ability
to increase the transendothelial electrical resistance of human renal
glomerular microvascular endothelial cells and human retinal endothelial
cells, which is a measure of the ability of DA-DKP to inhibit vascular
permeability. Id. Furthermore, Appellant argues, Example 3 of the
Specification demonstrates that DA-DKP has the ability to strengthen the
protective effects of sphingosine-1-phosphate (“SIP”) in retinal endothelial
cells (i.e., the ability to reverse endothelial dysfunction and to restore the
barrier function of endothelial cells). Id. Appellant also points to Example 4
of the Specification, which demonstrates that DA-DKP inhibits thrombin-
induced activation of Rho A. Id. According to Appellant, activation of Rho
A activity leads to prominent stress fiber formation in endothelial cells and
stimulation of endothelial cells with thrombin increases Rho GTP and
myosin phosphorylation, which is consistent with increased cell
contractility. Id. Appellant contends that inhibition of Rho A blocks this
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response and the loss of barrier function, demonstrating a critical role for
Rho A in vascular permeability. Id.
We are not persuaded by Appellant’s arguments. As an initial matter,
we agree with the Examiner that the combined references teach or suggest
all of the limitations of the claims. Briefly, Brown teaches that VEGF
promotes age-related macular degeneration and that VEGF-suppressing
agents are useful in the treatment of that condition. Brown 627–28. He
teaches that PAF promotes VEGF activity, that PAF antagonists inhibit
VEGF, and suggests that PAF regulation may be instrumental in suppressing
the early pathogenesis of exudative age-related macular degeneration. He ¶¶
1, 3, 4. Bar-Or ’543 teaches that: “(DA-DKP) inhibits PAF activity” and
that “[t]his inhibition appears to be due to the binding of DA-DKP to both
PAF and PAF receptors.” Bar-Or ’543 col. 3, ll. 32–34. We agree with the
Examiner that a person of ordinary skill in the art, understanding the
teachings of the cited references, would conclude that it would be obvious to
use the claimed diketopiperazines to suppress VEGF activity in the
treatment of age-related macular degeneration, particularly in view of the
direct suggestions of He.
Appellant argues, however, that there would have been no motivation
for a person of ordinary skill to combine the references, in part because
VEGF inhibitors have already been shown to be successful in the treatment
of macular degeneration and that, consequently, there would be no
motivation to seek another treatment. We do not find this argument
persuasive: we agree with the Examiner that investigators often seek new
methods of treatment for diseases, particularly those of an aging population,
because new treatment methods may confer new advantages. See Ans. 5.
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We conclude that seeking new treatments for a known disease would have
been sufficient motivation for a person of ordinary skill to combine the
references
Appellant also argues that DA-DKP has an activity that is independent
of VEGF activity and that is also effective in the treatment of endothelial
cells to inhibit vascular permeability. App. Br. 10 (citing Spec. Ex. 1, 2).
Although this may very well be true, it is not relevant to our obviousness
analysis, which looks to what the cited prior art would have taught or
suggested to a person of ordinary skill at the time of filing. As we have
explained, the combination of Brown, He, and Bar-Or ’543 would have
taught or suggested to a person of ordinary skill the use of DA-DKP to
suppress PAF activity as a means of inhibiting VEGF upstream and thus
treating age-related macular degeneration.
Furthermore, Appellant’s claims are directed to the treatment of
macular degeneration via the administration of, inter alia, DA-DKP.
Whether DA-DKP works via suppression of VEGF, a direct effect on
endothelial cells to inhibit vascular permeability, or both is immaterial to the
claimed method, because the scope of the claim recites only the use of DA-
DKP to treat macular degeneration. The newly discovered property of DA-
DKP discovered by Appellant is not sufficient to overcome the Examiner’s
prima facie conclusion that the cited prior art teaches or suggests the use of
DA-DKP in the treatment of age-related macular degeneration, even if by a
different, but nevertheless plausible, mechanism. Whether DA-DKP
inherently possessed unknown properties at the time of filing does not alter
the Examiner’s conclusion that a person of ordinary skill in the art would
have found the claimed method obvious over the teachings and suggestions
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of the prior art. See, e.g., In re Oelrich, 666 F.2d 578, 581 (C.C.P.A. 1981)
(“[M]ere recitation of a newly discovered function or property, inherently
possessed by things in the prior art, does not distinguish a claim drawn to
those things from the prior art”).
Finally, we are not persuaded by Appellant’s conclusory allegation
that the Examiner impermissibly employed hindsight reasoning.
Any judgment on obviousness is in a sense necessarily a
reconstruction based upon hindsight reasoning, but so long as it
takes into account only knowledge which was within the level of
ordinary skill at the time the claimed invention was made and
does not include knowledge gleaned only from applicant’s
disclosure, such a reconstruction is proper.

In re McLaughlin, 443 F.2d 1392, 1395 (C.C.P.A. 1971). Appellant points
to no evidence to show that the Examiner relied upon knowledge that could
have come only from Appellant’s Specification and not from the prior art.
We consequently affirm the Examiner’s rejection upon this ground.

B. Rejection of claim 1 and 3 over Bar-Or ’543 and Yasukawa under 35
U.S.C. § 103(a)

Issue
Appellant argues that the Examiner erred in concluding that, because
the teachings of Yasukawa link anti-inflammatory treatments to treatment of
age-related macular degeneration, it would have been obvious to a person of
ordinary skill in the art to use DA-DKP, as taught by Barr ’543 to treat age-
related macular degeneration by targeting the inflammation that causes it.
App. Br. 11.

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Analysis
The Examiner finds that Bar-Or teaches using diketopiperazines to
inhibit inflammation. Final Act. 6 (Bar-Or ’543 claims 8, 11, 13).
The Examiner finds that Yasukawa is directed to the relationship
between inflammation and age-related macular degeneration. Final Act. 6.
The Examiner finds that Yasukawa teaches that anti-inflammatory therapy
can stop the progression of exudative age-related macular degeneration. Id.
(citing Yasukawa 110).
The Examiner therefore concludes that it would have been obvious to
a person of ordinary skill to use the compositions of Bar-Or ’543 to treat
age-related oxidative degeneration by targeting the inflammation that causes
it. Final Act. 6. The Examiner further concludes that, because inflammation
plays a key role in the disorder, as taught by Yasukawa, a skilled artisan in
would have had a reasonable expectation of success in combining the
references to arrive at the claimed invention.
Appellant argues that there is no teaching or suggestion in Yasukawa
concerning any specific anti-inflammatory agents, nor any guidance as to
how to select an anti-inflammatory agent out of the numerous anti-
inflammatory agents known to those of skill in the art, nor any
demonstration that any specific anti-inflammatory agent is actually effective
in treating AMD. App. Br. 12. Appellant contends that, because there is no
teaching or suggestion in Bar-Or ’543 concerning optical disorders, there is
no reason one of skill in the art would select, out of the numerous
possibilities of anti-inflammatory agents, DA-DKP for treating wet AMD,
based solely on the combination of the teachings of Bar-Or ’543 and
Yasukawa.
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We are not persuaded by Appellant’s argument. Yasukawa teaches:
Immediately after birth, however, eyes continuously fight against
aging (oxidative stress) due to light exposure, possibly using
inflammatory processes within ‘physiological’ response during
middle age or later life. Once aging overcomes the anti-aging
responses, eyes may develop CNV [choroidal
neovascularization] as a pathological inflammatory response, or
lead to dry AMD [age-related macular degeneration]. Anti-
inflammatory therapy can stop the progression of exudative
AMD and, also, may stop the physiological anti-aging responses,
subsequently increasing the risk of dry AMD.

Yasukawa 110 (emphasis added). Yasukawa provides no teaching of what
may constitute “anti-inflammatory therapy,” nor does it teach or suggest any
anti-therapeutic agents that could prove effective in “stop[ping] the
progression of exudative AMD.”
However, Bar-Or ’543 teaches that: “(DA-DKP) inhibits PAF
activity” and that “[t]his inhibition appears to be due to the binding of DA-
DKP to both PAF and PAF receptors.” Bar-Or ’543 col. 3, ll. 32–34. Bar-
Or ’543 also teaches that:
PAF has been reported to play a role in a variety of diseases and
conditions. These diseases and conditions include acute
respiratory distress syndrome, allergies, arthritis, asthma,
autoimmune diseases, bronchitis, cardiovascular disease,
Crohn's disease, cystic fibrosis, emphysema, gastrointestinal
ulceration, inflammation, inflammatory bowel disease, ischemia,
multiple organ dysfunction syndrome, myocardial infarction,
neoplastic diseases, ophthalmic inflammation, pain, psoriasis,
respiratory infections, sepsis, shock, and ulcerative colitis. PAF
also mediates platelet aggregation. The diketopiperazines of
formula (1) can be used to treat any of these diseases and
conditions and any other diseases and conditions in which PAF
plays a role.

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Id. at col. 10, ll. 24–36 (emphasis added). Therefore, and contrary to
Appellant’s assertion, Bar ’543 teaches that PAF may cause ophthalmic
inflammation and suggests that inhibition of PAF by DA-DKP may be
useful in treating such ophthalmic inflammation, which Yasukawa teaches is
likely to be a cause of age-related macular degeneration.
We therefore agree with the Examiner that a person of ordinary skill
would understand that DA-DKP could be used to treat the ophthalmic
inflammation that Yasukawa teaches is a cause of PAF-induced age-related
macular degeneration. We consequently affirm the Examiner’s rejection
upon this ground.

C. Rejections of claims 1 and 3 over Bar-Or ’238 and Yasukawa under
35 U.S.C. § 103(a)

Bar-Or ’238 teaches that: “The invention provides a method of
inhibiting the effects of platelet activating factor (PAF). For instance, a
disease or condition mediated by PAF (particularly inflammation) can be
treated or platelet aggregation can be inhibited.” Bar-Or ’238 Abstr.
Specifically, Bar-Or teaches that:
PAF has been reported to play a role in a variety of diseases and
conditions. These diseases and conditions include acute
respiratory distress syndrome, allergies, arthritis, asthma,
autoimmune diseases, bronchitis, cardiovascular disease,
Crohn's disease, cystic fibrosis, emphysema, gastrointestinal
ulceration, inflammation, inflammatory bowel disease, ischemia,
multiple organ dysfunction syndrome, myocardial infarction,
neoplastic diseases, ophthalmic inflammation, pain, psoriasis,
respiratory infections, sepsis, shock, and ulcerative colitis. PAF
also mediates platelet aggregation.

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Bar-Or ’238 (emphasis added). Bar-Or ’238’s teachings are, in this respect,
identical to those of Bar-Or ’543 discussed supra, and, for the reasons we
have explained in Section B, we similarly affirm the Examiner’s rejection
upon this ground.

D. Rejection of claims 1 and 3 over Yasukawa and Bar-Or ’705 under 35
U.S.C. § 103(a)

Bar-Or ’705 is directed to: “a method of treating T-cell mediated
diseases and a method of inhibiting the activation of T-cells using certain
diketopiperazines.” Bar-Or ’705 Abstr. Bar-Or ’705 teaches that such T-
cell-mediated diseases include:
[G]raft rejection, graft versus host disease, unwanted delayed-
type hypersensitivity reactions (such as delayed-type allergic
reactions), T-cell mediated pulmonary diseases, and autoimmune
diseases. T-cell mediated pulmonary diseases include
sarcoidosis, hypersensitivity pneumonitis, acute interstitial
pneumonitis, alveolitis, pulmonary fibrosis, idiopathic
pulmonary fibrosis and other diseases characterized by
inflammatory lung damage. Autoimmune diseases include
multiple sclerosis, neuritis, polymyositis, psoriasis, vitiligo,
Sjogren’s syndrome, rheumatoid arthritis, Type 1 diabetes,
autoimmune pancreatitis, inflammatory bowel diseases (e.g.,
Crohn’s disease and ulcerative colitis), celiac disease,
glomerulonephritis, scleroderma, sarcoidosis, autoimmune
thyroid diseases (e.g., Hashimoto’s thyroiditis and Graves
disease), myasthenia gravis, Addison's disease, autoimmune
uveoretinitis, pemphigus vulgaris, primary biliary cirrhosis,
pernicious anemia, and systemic lupus erythematosis.

Bar-Or ’705 ¶ 41. Bar-Or ’705, however, does not expressly or implicitly
teach or suggest treating inflammatory or other conditions of the eye.
Although Bar-Or ’705 teaches that DA-DKP may be used to inhibit
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inflammation generally (see claim 102) we conclude that this alone is
insufficient to create a nexus with the teachings of Yasukawa that would
lead a person of ordinary skill to combine the references to use DA-DKP for
the treatment of age-related macular degeneration. We therefore reverse the
Examiner’s rejection upon this ground.

E. Rejection of claims 1 and 3 over claim 41 Bar-Or ’238 and Yasukawa
under the nonstatutory doctrine of obviousness-type double patenting.

Claim 41 of Bar-Or ’238 recites: “A pharmaceutical composition for
inhibiting inflammation comprising a pharmaceutically-acceptable carrier
and an amount of active ingredient effective to inhibit inflammation,
wherein the active ingredient is 3-methyl-2, 5-diketopiperazine-6-acetic acid
or a physiologically-acceptable salt thereof.” The Examiner finds that Bar-
Or ’238 teaches compositions of Appellant’s elected species, and concludes
that it would be obvious to use the formulations of the competing claims to
treat age-related oxidative degeneration by targeting the inflammation that
causes it. Final Act. 12.
We are not persuaded by the Examiner’s reasoning. Claim 41 of Bar-
Or ’238 recites a composition that can “effectively inhibit inflammation.”
However, we find that the term “inflammation” is so broad that there is
insufficient nexus between that language and the teachings of Yasukawa that
would lead a person of ordinary skill in the art to have a reasonable
expectation of success in using the compositions of claim 41 as “anti-
inflammation therapy”, as taught by Yasukawa, to treat age-related macular
degeneration.
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Furthermore, we are precluded from using the language of Bar-Or
’238’s Specification, including “ophthalmic inflammation” in our analysis.
See Eli Lilly and Co. v. Teva Parenteral Meds., Inc., 689 F.3d 1368, 1378–
79 (Fed. Cir. 2012):
As a general rule, obviousness-type double patenting
determinations turn on a comparison between a patentee's earlier
and later claims, with the earlier patent's written description
considered only to the extent necessary to construe its claims.
This is so because the nonclaim portion of the earlier patent
ordinarily does not qualify as prior art against the patentee and
because obviousness-type double patenting is concerned with the
improper extension of exclusive rights—rights conferred and
defined by the claims.

(Emphasis in original and internal citation omitted). Because we conclude
that the mere mention of inhibiting inflammation in claim 41 relates
generally to a genus so broad compared to the specific inflammation that
may cause age-related macular degeneration, we reverse this rejection.

F. Rejection of claims 1 and 3 over claims 8, 11, and 13 of Bar-Or ’543
and Yasukawa under the nonstatutory doctrine of obviousness-type
double patenting

Claim 8 of Bar-Or ’543 recites, in relevant part: “A method of
inhibiting inflammation comprising administering to an animal in need
thereof an effective amount of a compound of the formula:

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…” Claim 11 recites: “The method of claim 10 wherein R1 is –
CH2COOH.” Claim 13 recites: “The method of claim 12 wherein R2 is the
side chain of alanine.”
As we have explained in the preceding section, the mere use of the
term “inhibiting inflammation” is insufficient to provide a person of
ordinary skill in the art a reasonable expectation of success in using the
claimed composition as “anti-inflammation therapy” sufficient to treat age-
related macular degeneration, as taught by Yasukawa. We therefore reverse
the Examiner’s rejection on this ground.

G. Rejection of claims 1, 3, and 45 over claim 102 of Bar-Or ’705 and
Yasukawa under the nonstatutory doctrine of obviousness-type double
patenting

Claim 102 of Bar-Or ’705 recites:
A method of inhibiting inflammation, comprising administering
to an animal in need thereof a pharmaceutical composition
comprising an alanine-aspartic acid diketopiperazine (DA-DKP)
and a component selected from the group consisting of caprylic
acid, N-acetyl tryptophan and combinations thereof, wherein the
composition is an isotonic aqueous solution, and wherein the
composition is formulated for administration as a drop.

For the same reasons we have explained in Sections E and F supra,
we reverse the Examiner’s rejection on this ground.

H. Rejection of claims 1 and 3 over claim 1 of Bar-Or ’496 and Nicolson
under the nonstatutory doctrine of obviousness-type double patenting

Claim 1 of Bar-Or ’496 recites:
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A method of treating metabolic syndrome in an animal
comprising administering to the animal an effective amount of
an active ingredient, wherein the active ingredient comprises a
diketopiperazine, a prodrug of a diketopiperazine or a
pharmaceutically-acceptable salt of either of them, wherein the
diketopiperazine has the formula:

I

wherein R1 is the side chain of aspartic acid, and R2 is the side
chain of alanine.
The Examiner finds that Nicholson teaches that metabolic syndrome
has long term effects resulting in diabetic retinopathy, which can cause
macular edema and damage or loss of vision. Final Act. 16 (citing Nicolson
1360). The Examiner concludes that it would have been obvious to a person
of ordinary skill that treatment of metabolic syndrome would also treat
diabetic macular edema. The Examiner also concludes that a skilled artisan
would have had a reasonable expectation of success in combining the
references because the two disorders are related. Id.
Although we are generally prohibited from considering the
specification in an obviousness-type double patenting analysis, we may use
the specification to construe or define claim terms. Eli Lilly, 689 F.3d at
1378. Bar-Or ’496 defines the claim term “metabolic syndrome” as: “[A]
complex of risk factors for cardiovascular disease and type 2 diabetes. The
most widely recognized of the risk factors are atherogenic dyslipidemia,
elevated blood pressure and elevated plasma glucose. In addition, patients
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with these characteristics commonly manifest a prothrombotic state and a
proinflammatory state.” Bar-Or ’496 col. 1, ll. 38–43.
Nicolson teaches that:
In late-stage diabetes [an outcome of metabolic syndrome] an
important complication is the presence of diabetic neuropathies.
The most common of these is diabetic sensory neuropathy
associated with small fiber or unmyelinated fiber neuropathy,
which results in progressive sensory loss. It can also result in
pain, hyperestesia and parestesias. When this affects both
somatic and autonomic peripheral nerves, it is termed diabetic
polyneuropathy, and this can result in damage to sensory, motor
and autonomic nerves. Oxidative stress and mitochondrial
dysfunction are thought to be the most overriding causes of
diabetic neuropathies, but other factors, such as genetics,
hyperglycemia and neurotrophin synthesis, are also important
factors.

(internal reference omitted).
Neither Nicolson nor claim 1 of Bar-Or ’496 teaches or suggests “age-
related macular degeneration” and although Nicolson teaches that an
outcome of metabolic syndrome can be diabetic neuropathies, the references
do not establish that diabetic neuropathies can include age-related macular
degeneration or the mechanisms that can induce it. We consequently
conclude that a person of ordinary skill would not have understood that
claim 1 of Bar-Or ’496 and the teachings of Nicolson teach or suggest the
limitations of the claims on appeal, and we reverse the Examiner’s rejection
upon this ground.

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21
I. Rejection of claims 1, 3, 29, and 45 over claims 1, 2, and 4 of the ’218
application and He under the nonstatutory doctrine of obviousness-
type double patenting

Claim 1 of the ’218 application recites, in relevant part: “A method of
treating a respiratory condition selected from the group consisting of acute
respiratory distress syndrome, bronchitis, cystic fibrosis, emphysema and
respiratory infection, comprising administering to an animal [DA-DKP].”
Claims 2 and 4 also relate to the structure of the claimed composition.
The Examiner finds that He teaches that, in the context of exudative
age related macular degeneration, VEGF production is promoted by PAF
and that PAF antagonists reduce VEGF production. Final Act. 17.
We are not persuaded. Claim 1 of the ’218 application relates to the
treatment of: “acute respiratory distress syndrome, bronchitis, cystic
fibrosis, emphysema and respiratory infection.” He teaches that inhibition
of PAF may in turn inhibit VEGF, which is implicated in the induction of
age-related macular degeneration. We conclude that there is no express or
implicit nexus between the cited claims of the ’218 application and He, such
that a person of ordinary skill in the art would conclude that it would have
been obvious to combine the claims with the teachings of He to arrive at
Appellant’s claimed invention. We therefore reverse.

DECISION
The Examiner’s rejection of claims 1, 3, 28, 29, and 45 under 35
U.S.C. § 103(a) is affirmed.
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22
The Examiner’s rejection of claims 1, 3, 29, and 45 as unpatentable
under the nonstatutory doctrine of obviousness-type double patenting is
reversed.
No time period for taking any subsequent action in connection with
this appeal may be extended under 37 C.F.R. § 1.136(a)(1)(iv).

AFFIRMED