Janet C. Blanks et al.

Patent Trials and Appeals Board

Feb 18, 2020

14861009 - (D) (P.T.A.B. Feb. 18, 2020)

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.
14/861,009 09/22/2015 Janet C. Blanks 7018-0023 9908
112994 7590 02/18/2020
CHS Pharma, Inc
5425 Park Central Court
Suite 111
Naples, FL 34109
EXAMINER
FAY, ZOHREH A
ART UNIT PAPER NUMBER
1617
NOTIFICATION DATE DELIVERY MODE
02/18/2020 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):
sakptomail@iplawpro.com
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
__________

BEFORE THE PATENT TRIAL AND APPEAL BOARD
__________

Ex parte JANET C. BLANKS,
HOWARD MALCOLM PRENTICE, and
HERBERT WEISSBACH
__________

Appeal 2019-001442
Application 14/861,009
Technology Center 1600
__________

Before RICHARD M. LEBOVITZ, JEFFREY N. FREDMAN, and
RYAN H. FLAX, Administrative Patent Judges.

FREDMAN, Administrative Patent Judge.

DECISION ON APPEAL
This is an appeal under 35 U.S.C. § 134 involving a method of
treating oxidative stress-induced degeneration of photoreceptor cells and
retinal pigment epithelial cells in an eye of a mammalian subject with dry
macular degeneration.1,2 The Examiner rejected the claims as obvious. We
have jurisdiction under 35 U.S.C. § 6(b). We reverse.

1 We use the word “Appellant” to refer to “applicant” as defined in
37 C.F.R. § 1.42. Appellant identifies the Real Party in Interest as CHS
Pharma, Inc. (see Br. 3).
2 We note that this case is related to US application 13/463,440, Appeal
2015-004241, where the Examiner was affirmed.
Appeal 2019-001442
Application 14/861,009

2

Statement of the Case
Background
“The visual impairment in advanced age-related macular degeneration
(AMD) is associated with photoreceptor loss in the macula, the central area
of the retina responsible for acuity and color vision” (Spec. ¶ 4). “A major
external agent responsible for inflicting oxidative damage upon the RPE
[retinal pigment epithelium] layer of the human eye is photooxidative
damage induced by visible or ultraviolet (UV) light” (id.). “Based upon the
pattern of progression and pathophysiology, macular degeneration can be
divided into two basic types: ‘dry’ and ‘wet[.]’ Approximately 85% to 90%
of the cases of AMD are the ‘dry’ (atrophic) type” (id. ¶ 5). “It has been
discovered that sulindac can protect photoreceptor and RPE cells in a subject
from degenerating in response to photooxidative insults” (id. ¶ 6).
The claims
Claims 1 and 4–13 are on appeal. Claim 1, the sole independent
claim, is representative, and reads as follows:
1. A method of treating oxidative stress-induced
degeneration of photoreceptor cells and retinal pigment
epithelial cells in an eye of a mammalian subject with dry
macular degeneration, the method comprising the step of
administering an ophthalmically-acceptable pharmaceutical
composition comprising a sulindac agent to the eye of the
subject in an amount sufficient to reduce oxidative stress-
induced degeneration of photoreceptor cells and retinal pigment
epithelial cells in the eye of a mammalian subject, wherein the
oxidative stress-induced degeneration of photoreceptor cells
and retinal pigment epithelial cells in the eye of a mammalian
subject is reduced after the step of administering the
pharmaceutical composition.

Appeal 2019-001442
Application 14/861,009

3

The issue
The Examiner rejected claims 1 and 4–13 under 35 U.S.C. § 103(a) as
obvious over D’Amato3 and Simmons4 (Final Act. 2–6).
The Examiner finds D’Amato teaches
the use of non-steroidal anti-inflammatory compounds . . . for
inhibiting angiogenesis related disorders. See the abstract. The
treatment of angiogenic conditions, such as macular
degeneration and retinopathy is taught in Para [0007], [0029],
[0033] and claim 20. The use of sulindac for the treatment of
angiogenesis dependent disorders is taught in Para [0097] . . .
The ophthalmic use is taught in Para [0101].

(Final Act. 3). The Examiner finds Simmons teaches “ophthalmic
formulation using analgesics, such as opioids and non-opioids” (id.). The
Examiner finds it obvious to combine these components because Simmons
teaches “the use of DMSO in a composition containing sulindac as old and
well known” (id. 4).
The issue with respect to this rejection is: Does a preponderance of
the evidence support the Examiner’s conclusion that D’Amato and Simmons
render the claims obvious?
Findings of Fact
1. D’Amato explains that in “age-related macular degeneration,
the associated visual problems are caused by an ingrowth of choroidal
capillaries through defects in Bruch’s membrane” (D’Amato ¶ 7). Therefore
D’Amato teaches “methods and compositions for preventing unwanted
angiogenesis in a human” where “[d]iseases associated with

3 D’Amato, R., US 2003/0191098 A1, published Oct. 9, 2003.
4 Simmons et al., US 2007/0116730 A1, published May 24, 2007.
Appeal 2019-001442
Application 14/861,009

4

retinal/choroidal neovascularization include . . . macular degeneration”
(D’Amato ¶¶ 2, 8).
2. D’Amato teaches “treating certain ocular neovascular diseases
such as macular degeneration. The compounds which are contemplated as
part of the present invention preferably can be given orally to the patient and
thereby halt the progression of the disease” (D’Amato ¶ 29).
3. D’Amato teaches “the invention also includes the inhibition of
angiogenesis and the treatment of angiogenesis dependent diseases by
administering antiinflammatory compounds . . . Examples of NSAIDs which
may be used in the invention include . . . sulindac, sulindac sulfone, sulindac
sulfide” (D’Amato ¶¶ 95–96).
4. D’Amato teaches “formulations include those suitable for . . .
ophthalmic . . . administration” (D’Amato ¶ 101).
5. Example 9 of D’Amato teaches a “Corneal Micropocket Assay”
where neovascularization was induced in mouse corneas as “pellets
containing bFGF were implanted 1.0-1.2 mm from the limbal vessels, while
the pellets containing VEGF were implanted 0.5-0.7 mm from the limbal
vessels” (D’Amato ¶¶ 147–148). “The mice were then treated with varying
doses of antiinflammatory drugs as shown in the table” reproduced in part,
below:

(D’Amato ¶ 149).
Appeal 2019-001442
Application 14/861,009

5

6. Example 11 of D’Amato teaches another “Corneal Micropocket
Assay” where different forms of Sulindac were administered to corneas of
mice with bFGF implanted and the results of inhibition of corneal
neovascularization by Sulindac are shown in the following table

(D’Amato ¶¶ 154–156).
7. D’Amato teaches “[f]or oral administration to humans, a dosage
of between approximately 0.1 to 300 mg/kg/day, preferably between
approximately 0.5 and 50 mg/kg/day, and most preferably between
approximately 1 to 10 mg/kg/day, is generally sufficient” (D’Amato ¶ 100).
8. Simmons teaches “the present invention allows for the
inclusion of a non-opioid analgesic, such as an NSAID. Preferred NSAIDs,
include . . . sulindac” (Simmons ¶ 28).
9. Simmons teaches “[s]uitable penetration enhancers include, but
are not limited to . . . dimethyl sulfoxide (DMSO)” (Simmons ¶ 33).
10. Simmons teaches “[a]n appropriate buffering agent may be
added to maintain the pH” (Simmons ¶ 39).
11. Schwartz,5 cited by Appellant, teaches “[m]acular degeneration
is categorized as either dry (atrophic) or wet (neovascular). The dry form is
more common than the wet, with about 90% of AMD patients diagnosed

5 Schwartz et al., US 7,381,404 B2, issued June 3, 2008.
Appeal 2019-001442
Application 14/861,009

6

with dry AMD. The wet form of the disease usually leads to more serious
vision loss” (Schwartz 1:35–39).
12. Schwartz teaches “[i]n the dry form, there is a breakdown or
thinning of the retinal pigment epithelial cells (RPE) in the macula, hence
the term ‘atrophy’” (Schwartz 1:40–42).
13. Schwartz teaches:
Wet AMD occurs when new vessels form and grow through
Bruch’s membrane into the sub-RPE and subretinal space. This
neovascular tissue is very fragile and hyperpermeable.
Frequently, it bleeds causing damage to the overlying retina.
As the blood organizes, functional macular tissue is replaced by
scar tissue. To prevent visual loss, it would be desirable to
intervene therapeutically prior to the development of
neovascularization.
(Schwartz 1:60–67).
Principles of Law
A prima facie case for obviousness “requires a suggestion of all
limitations in a claim,” CFMT, Inc. v. Yieldup International Corp., 349 F.3d
1333, 1342 (Fed. Cir. 2003) and “a reason that would have prompted a
person of ordinary skill in the relevant field to combine the elements in the
way the claimed new invention does.” KSR Int’l Co. v. Teleflex Inc., 550
U.S. 398, 418 (2007).
Analysis
Appellant contends:
D’Amato does not expressly define what is meant by its usage
of the term “macular degeneration.” Nonetheless, by reading
the description portion of this patent, it is abundantly clear that
the inventors thereof intended this term to mean only wet
AMD, and not include dry AMD. The description part of this
Appeal 2019-001442
Application 14/861,009

7

application uses the term “macular degeneration” in 4 places,
without specifying wet or dry.

(Appeal Br. 7). Appellant contends D’Amato “states that its invention is
related to the treatment of diseases that are mediated by angiogenesis
(defined therein as ‘the generation of new blood vessels into a tissue or
organ’), but does not mention anything about targeting oxidative stress” (id.
7–8). Appellant concludes
D’Amato fails to provide any motivation for the skilled artisan
to try to see whether sulindac might be useful in the treatment
of dry macular degeneration because the mechanism of action
of sulindac described in D’Amato is to inhibit
neovascularization - a process not involved in the degeneration
of retinal cells in dry macular degeneration.
(Id.).
The Examiner responds
that dry macular degeneration is the preliminary stage of wet
macular degeneration as evidenced by Exhibit A (Schwartz et
al.) presented by the appellant. Schwartz in column 9, lines 25-
36 teaches that the thickening of Bruch’s membrane as a result
of lipid and protein deposition precedes the neovascularization.
Therefore, it is the examiner’s position that even if sulindac is
used by D’Amato for the treatment of wet macular
degeneration, since the dry macular degeneration which is
manifests by the deposition of lipid and protein on the Bruch’s
membrane precedes wet macular degeneration and already
exists in the eye, the treatment of wet macular degeneration by
sulindac is expected to treat the dry macular degeneration,
which precedes the neovascularization.
(Ans. 6).
We agree with Appellant. There is no evidence in the publications
cited by the Examiner establishing that dry macular degeneration is
Appeal 2019-001442
Application 14/861,009

8

associated with neovascularization. Although Schwartz discloses that wet
macular degeneration is associated with neovascularization, the reference
does not state this defect is also associated with dry AMD (FF 11–13).
D’Amato’s teaches treatment of diseases associated with retinal/choroidal
neovascularization and mentions macular degeneration, but does not identify
if the type of macular degeneration is wet or dry (FF 1–3). Because only
wet macular degeneration is associated with angiogenesis and
neovascularization, the evidence reasonably supports a finding that
D’Amato’s suggested treatment of macular degeneration caused by
neovascularization using compounds including sulindac only applies to wet
macular degeneration, not dry (See FF 1–3).
The Examiner does not provide either reasons or evidence that
demonstrates the applicability of any of the compounds of either D’Amato
or Simmons to dry macular degeneration, but rather contends that because
dry macular degeneration may be a condition precedent to wet macular
degeneration, the same treatment would be applicable. However, the
Examiner’s speculation that a wet macular degeneration treatment will also
treat dry macular degeneration lacks any evidentiary support in the record,
and is not a necessary expectation. Just as a broken leg may sometimes
result in sepsis, treatment of sepsis using antibiotics will not necessarily treat
a broken leg.6 The Examiner does not establish a sufficiently persuasive

6 While we do not rely on this evidence, this situation occurred to an NFL
football player where “the initial surgery to repair the breaks was successful,
with several plates inserted into his leg to align the bones, and he was almost
ready to leave the hospital a few days after the injury when sepsis set in.”
See https://www.washingtonpost.com/sports/2020/02/01/alex-smith-fully-
Appeal 2019-001442
Application 14/861,009

9

causal link between dry and wet macular degeneration to demonstrate a
prima facie case of obviousness.
Conclusion of Law
The evidence of record does not support the Examiner’s conclusion
that D’Amato and Simmons render the claims obvious 8.

CONCLUSION
In summary:
Claims
Rejected
35 U.S.C. § Reference(s)/Basis Affirmed Reversed
1, 4–13 103 D’Amato, Simmon 1, 4–13
Overall
Outcome
1, 4–13

REVERSED

details-his-leg-injury-first-time-says-he-is-lucky-be-alive/ (Accessed Feb.
10, 2020).