Ex Parte Günther et al

Patent Trials and Appeals Board

Jan 17, 2019

14427927 - (D) (P.T.A.B. Jan. 17, 2019)

UNITED STA TES p A TENT AND TRADEMARK OFFICE
APPLICATION NO. FILING DATE
14/427,927 03/12/2015
50446 7590 01/22/2019
HOXIE & ASSOCIATES LLC
75 MAIN STREET, SUITE 203
MILLBURN, NJ 07041
FIRST NAMED INVENTOR
Bernhard Gunther
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.
NVL-09-US 4227
EXAMINER
CARTER, KENDRA D
ART UNIT PAPER NUMBER
1627
NOTIFICATION DATE DELIVERY MODE
01/22/2019 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):
HoxiePatentMail@hoxpat.com
HoxiePatentMail@gmail.com
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
BEFORE THE PATENT TRIAL AND APPEAL BOARD
Ex parte BERNHARD GUNTHER, BASTIAN THEISINGER,
SONJA THEISINGER, and DIETER SCHERER
Appeal2018-005066
Application 14/427 ,927
Technology Center 1600
Before MICHAEL J. FITZPATRICK, ULRIKE W. JENKS, and
TIMOTHY G. MAJORS, Administrative Patent Judges.
FITZPATRICK, Administrative Patent Judge.
DECISION ON APPEAL
Bernhard Gunther, Bastian Theisinger, Sonja Theisinger, and Dieter
Scherer ("Appellants") 1 appeal under 35 U.S.C. § 134(a) from the
Examiner's final decision rejecting claims 16-18, 22, 24, 25, and 28-30.
We have jurisdiction under 35 U.S.C. § 6(b).
We affirm.
1 The real party in interest is identified as Novaliq GmbH. Appeal Br. 2.
Appeal2018-005066
Application 14/427 ,927
STATEMENT OF THE CASE
The Specification
A human eye has on the surface of its cornea a tear film, which is a
dynamic structure composed of an innermost mucous layer, an intermediate
aqueous layer, and an outermost lipid layer. Spec. 1:22-2: 15.
The outermost lipid layer is:
formed from meibum (a complex mixture of polar and non-polar
lipids including wax and cholesterol esters, phospholipids, di-
and tri-glycerides and hydrocarbons) secreted by the
[M]eibomian (tarsal) glands which are positioned at the tarsal
plates of the eyelids, and to some degree also by the glands of
Zeis which open into the eyelash follicles .... It is understood
that the blinking action helps to promote the spreading and
mixing of the lipids in the lipid layer. The major role of the lipid
layer is primarily to reduce the rate of evaporation of the aqueous
layer by evaporation, but its functions also include enhancing the
spreading of the tear film, forming a barrier to prevent tear film
contamination, and providing a clear optical surface. It has been
proposed that increased tear film stability is associated with a
thicker tear film lipid layer.
Spec. 2:15-28.
According to Appellants, their invention "is in the field of ophthalmic
compositions, in particular topical ophthalmic compositions which are useful
in the treatment keratoconjunctivitis sicca and/or [M]eibomian gland
dysfunction and symptoms associated therewith." Spec. 1: 1--4.
Keratoconjunctivitis sicca is a complex, multifaceted disease or
condition as described above. It is also known as dry eye
syndrome, dry eye disease (DED), or dysfunctional tear
syndrome. Aqueous-deficient DED, evaporative DED are within
the scope of keratoconjunctivitis sicca and form specific
subtypes thereof. Sjogren syndrome, lacrimal gland
insufficiency, [M]eibomian gland disease and Meibomian gland
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Application 14/427 ,927
dysfunction, and other conditions are also within the scope of
keratoconjunctivitis sicca, being direct or indirect causes thereof.
Spec. 9:26-32. "Meibomian gland dysfunction can often be characterized
by gland obstruction and clogging through hyperkeratinisation of the gland
and increased viscosity of the meibum." Id. at 4:7-9.
The specification discloses topically administering to the surface of a
patient's eyes semifluorinated alkanes, including F(CF2)6(CH2)sH ("F6H8")
which is the semifluorinated alkane recited in the independent claims. See,
e.g., Spec. 15:26-32, 16 (Table I). The semifluorinated alkane is
administered for "solubilizing meibum lipids and for removing abnormal
and obstructive meibum found in clogged [M]eibomian gland ducts." Id. at
15:31-32.
The Rejected Claims
All pending claims, namely claims 16-18, 22, 24, 25, and 28-30,
stand rejected. Final Act. 1. Independent claim 16 is representative and
reproduced below.
16. A method for solubilizing meibum and removing
abnormal and obstructive meibum from obstructed meibomian
gland ducts in a patient in need thereof, comprising
topically administering the semifluorinated alkane
F(CF2)6(CH2)sH (F6H8) to the cornea or conjunctiva of the eye
of the patient, wherein the semifluorinated alkane spreads over
the corneal surface or conjunctiva; and
wherein said semifluorinated alkane is administered in
the absence of any therapeutically effective amount of a
pharmaceutically active drug substance useful for the topical
ophthalmic treatment of keratoconjunctivitis sicca; and
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Application 14/427 ,927
wherein the patient has keratoconjunctivitis sicca which
is caused by meibomian gland dysfunction.
Appeal Br. 25.
The Appealed Rejections
The following rejections are before us for review:
1. claims 16-18, 22, and 24 provisionally for nonstatutory double
patenting over claims 18-29 of the '031 application2 in view of Blackie, 3
Gunther, 4 admitted prior art, 5 Troiano, 6 and Meinert (Final Act. 5); 7
2. claims 25 and 28-30 provisionally for nonstatutory double
patenting over claims 18-29 of the '031 application (Final Act. 8);
3. claims 16-18, 22, 24, 25, and 28-30 provisionally for
nonstatutory double patenting over claims 1-19 of the '306 application8 in
view of Blackie, Gunther, admitted prior art, Troiano, and Meinert (Final
Act. 9);
4. claims 16-18, 22, and 24 under 35 U.S.C. § I03(a) over
Blackie, Gunther, admitted prior art, Troiano, and Meinert (Final Act. 17);
and
2 US Application No. 15/428,031 ("the '031 application").
3 Caroline A. Blackie and Donald R. Korb, MGD: Getting to the Root Cause
of Dry Eye, Review of Optometry 1-12 (2012) ("Blackie").
4 EP 2,335,735 Al, published June 22, 2011 ("Gunther").
5 Page 2 of the Specification.
6 Pasquale Troiano and Gaspare Monaco, Effect of Hypotonic 0.4%
Hyaluronic Acid Drops in Dry Eye Patients: A Cross-Over Study, 27(10)
Cornea 1126-1130 (2008) ("Troiano").
7 US 6,262,126 B 1, issued July 17, 2001 ("Meinert").
8 US Application No. 15/280,306 ("the '306 application").
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Application 14/427 ,927
5. claims 25 and 28-30 under 35 U.S.C. § 103(a) over Blackie,
Gunther, admitted prior art, Troiano, and Meinert (Final Act. 22). 9
DISCUSSION
Rejection 1
The Examiner rejected claims 16-18, 22, and 24 provisionally for
nonstatutory double patenting over claims 18-29 of the '031 application in
view of Blackie, Gunther, admitted prior art, Troiano, and Meinert. Final
Act. 5. For this rejection, Appellants rely on the same arguments they
present for Rejection 4 (see Appeal Br. 23), which rejection we affirm
below. Thus, we also affirm this rejection.
Rejection 2
The Examiner rejected claims 25 and 28-30 provisionally for
nonstatutory double patenting over claims 18-29 of the '031 application.
Final Act. 8. For this rejection, Appellants do not present arguments. See
Appeal Br. 23. Instead, they indicate that they "will amend the copending
['031] application and/or file a terminal disclaimer in the present application
in order to address the Examiner's concerns." Id. Accordingly, we
summarily affirm this rejection.
Rejection 3
The Examiner rejected claims 16-18, 22, 24, 25, and 28-30
provisionally for nonstatutory double patenting over claims 1-19 of the '306
9 The Final Action contains an objection to claim 16 as well as rejections
under 35 U.S.C. § 112 ,r,r 2 and 4. Final Act. 3, 14--16. However, that
objection and those rejections were withdrawn in the Examiner's Answer.
Ans. 4.
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Application 14/427 ,927
application in view of Blackie, Gunther, admitted prior art, Troiano, and
Meinert. Final Act. 9. For this rejection, Appellants rely on the same
arguments they present for Rejection 4 (see Appeal Br. 23-24), which
rejection we affirm below. Thus, we also affirm this rejection.
Rejection 4
The Examiner rejected claims 16-18, 22, and 24 under 35 U.S.C.
§ 103(a) over Blackie, Gunther, admitted prior art, Troiano, and Meinert.
Final Act. 17. Appellants argue all of these claims together. Appeal Br. 4--
21. Accordingly, we select independent claim 16 as representative. See 3 7
C.F.R. § 4I.37(c)(l)(iv).
The Examiner found that Blackie teaches that Meibomian gland
dysfunction ("MGD") is the leading cause of dry eye and that obstructive
MGD results in inadequate lipid production for the formation of the lipid
layer of the tear film. Final Act. 17 ( citing Blackie 2). The Examiner
further found that, when obstructive MGD presents, the goal is to evacuate
the obstruction and other Meibomian gland material from the gland thereby
creating a new environment that offers the potential for normal gland
secretion. Id. at 18 (citing Blackie 4). The Examiner conceded that Blackie
"does not teach a method for solubilizing meibum and removing abnormal
and obstructive meibum from obstructed meibomian gland ducts with
specifically F6H8 wherein the semifluorinated alkane composition is in the
absence of a drug substance." Id.
The Examiner found that Gunther teaches a method of treating dry
eye by applying to the cornea a composition comprising a semifluorinated
alkane carrier, such as F6H8, and an active ingredient. Id. at 19 (citing
Gunther, [57], ,I44). The Examiner further found that Gunther observed that
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at least one tested semifluorinated alkane "exhibit[ ed] a positive effect on
the healing of damaged cornea similar to that ofhyaluronic acid." Gunther
iF5 (cited at Final Act. 19). 10
The Examiner relies on the specification's admission that meibum is a
"complex mixture of polar and nonpolar lipids including wax and
cholesterol esters, phospholipids, di- and tri-glycerides and hydrocarbons."
Final Act. 19.
Finally, the Examiner relies on Meinert as teaching the use of
semifluorinated alkanes in the eyes, including as a drug or washing solution,
and further teaching that such alkanes are soluble in hydrocarbons and their
derivatives and compounds with higher alkyl group contents such as liquid
paraffins, silicone oils, fatty acid esters and thus in meibum. Final Act. 19--
20 (citing Meinert 2:31-50, 3:54---60, 5:30-35).
The Examiner explains how and why the method of claim 16, for
example, would have been obvious to a person of ordinary skill in the art in
light of the cited prior art teachings. See Final Act. 20-22. To paraphrase,
according to the Examiner, the person of ordinary skill in the art would be
motivated to unclog solidified meibum in the Meibomian gland of a person
suffering from obstructive MGD, would know that semifluorinated alkanes
may be topically administered to the eyes safely to provide a therapeutic
effect, would know what meibum is made of, would know that semi-
fluorinated alkanes dissolve various known components that make up
meibum, would reasonably believe that such dissolution would unclog the
10 The Examiner also cites Troiano as evidence that hyaluronic acid is used
to treat dry eye patents by reducing the symptoms. Final Act. 19 ( citing
Troiano abstract).
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Meibomian gland, and would be motivated to try F6H8 as the
semifluorinated alkane because it is specifically identified in the prior art.
See id.
Appellants present arguments in opposition, but they are not
persuasive.
First, Appellants present a series of arguments that are not
commensurate with the rejection. In that regard, Appellants argue that the
claimed invention would not have been obvious because: (1) Gunther,
Troiano, and Meinert are directed to different mechanisms of dry eye
diseases than obstructive MGD (Appeal Br. 5-9); (2) Gunther and Troiano
are "[i]rrelevant" to the treatment of MGD-caused dry eye diseases (Appeal
Br. 10-12); and (3) none of the references teaches or suggests using a
chemical solvent to dissolve meibum (Appeal Br. 13).
The Federal Circuit has held the following:
Non-obviousness cannot be established by attacking references
individually where the rejection is based upon the teachings of a
combination of references. . . . [The reference] must be read, not
in isolation, but for what it fairly teaches in combination with the
prior art as a whole.
In re Merck & Co., 800 F.2d 1091, 1097 (Fed. Cir. 1986). Under Merck,
Appellants' entire series of arguments is unpersuasive because the
Examiner's rejection is not premised or dependent on any of Gunther,
Troiano, and Meinert being directed to obstructive MGD. The rejection
relies on those references as evidence that a person of ordinary skill in the
art would know that topical administration of semifluorinated alkanes to the
eyes is safe and provides therapeutic benefit to dry eye generally and that
semifluorinated alkanes dissolve various known components that make up
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Application 14/427 ,927
meibmn. See Final Act. 19-20. The rejection relies on Blackie for
providing the motivation to apply these teachings as a solution to obstructive
MGD. Id. at 18-22.
Next, Appellants present a series of arguments that there would not
have been a reasonable expectation of success in dissolving solidified
meibum and thereby unclogging the Meibomian gland using semi-
fluorinated alkanes. Appeal Br. 14--19. These arguments are not persuasive
in light of the Examiner's findings, which we adopt, that (1) "meibum [is] a
complex mixture of polar and non-polar lipids including wax and cholesterol
esters, phospholipids, di- and tri-glycerides and hydrocarbons" (Spec. 2:16-
18 (cited at Final Act. 7, 12, 19, 21, 24, 25); and (2) Meinert explicitly
teaches that "semifluorinated alkanes ... are soluble ... in hydrocarbons
and their derivatives and compounds with higher alkyl group contents ( e.g.,
liquid paraffins, silicone oils, fatty acid esters, etc.)." Meinert 2:31--42
( cited at Final Act. 20).
Appellants' arguments seek to cast doubt that a person of ordinary
skill in the art at the time of the claimed invention would have been certain
that semifluorinated alkanes would successfully unclog an obstructed
Meibomian gland. See, e.g., Appeal Br. 19 ("[T]he skilled artisan would
recognize that meibum might not dissolve with sufficient speed to unblock
the Meibomian gland during the fairly brief period of time before which the
SF A would be too diluted by tears to be effective."). "Obviousness does not
require absolute predictability of success .... For obviousness under § 103,
all that is required is a reasonable expectation of success." In re O 'Farrell,
853 F.2d 894, 903---04 (Fed. Cir. 1988). The Examiner has shown as much.
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Lastly, Appellants argue that the claimed invention is non-obvious as
evidenced by unexpected results. Appeal Br. 19--21. "[I]t is well settled that
unexpected results must be established by factual evidence. 'Mere argument
or conclusory statements in the specification does not suffice."' In re
Geisler, 116 F.3d 1465, 1470 (Fed. Cir. 1997) (quoting In re De Blauwe,
736 F.2d 699, 705 (Fed. Cir. 1984)). The factual evidence must have a
nexus with the claimed invention. Wyers v. Master Lock Co., 616 F.3d
1231, 1246 (Fed. Cir. 2010) ("For objective [ evidence of secondary
considerations] to be accorded substantial weight, its proponent must
establish a nexus between the evidence and the merits of the claimed
invention."). Additionally, such factual evidence must show results that are
unexpected relative to the closest prior art. In re Baxter Travenol Labs., 952
F.2d 388, 392 (Fed. Cir. 1991) ("[W]hen unexpected results are used as
evidence of nonobviousness, the results must be shown to be unexpected
compared with the closest prior art.").
In a first variation of their unexpected results argument, Appellants
state:
As demonstrated in Appellant's Table 2 of the
specification, pure F6H8 has an unexpected ability to spread out
over the surface of the eye much more than other pure SF As, for
example, F4H5. The data demonstrates that SFAs generally are
unexpectedly superior to hydrocarbons and perfluorocarbons in
their ability to spread into a monolayer film, and that F6H8 in
particular is unexpectedly superior in this capacity compared to
F4H5.
Appeal Br. 19.
Appellants have not shown a nexus between this evidence, which
shows that 50 µL F6H8 spreads out over 12.89 cm2 of glass surface whereas
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the same amount ofF4H5 spreads out over only 7.54 cm2 of the same glass
surface (Spec. 19 (Table 2)), and the claimed invention, which does not
require any particular degree or amount of spreading out. Claim 16 recites
"topically administering the semifluorinated alkane F(CF2) 6(CH2) 8H (F6H8)
to the cornea or conjunctiva of the eye of the patient, wherein the
semifluorinated alkane spreads over the corneal surface or conjunctiva."
Claim 16 does not require the topically-administered F6H8 to spread out
over the entire corneal surface to any particular degree such as by any
specified amount of surface area or within any specified amount of time.
Further, if Appellants recognized any unexpected results from using
F6H8 in particular, it is not specifically evidenced in their application as
filed. In that regard, the conclusion made by Appellants, based on the data
of Table 2, was not that F6H8 in particular demonstrated unexpectedly good
results. Rather, what the application describes, contrary to what is now
claimed in claim 1, is that using two SF As is better than any one SF A.
Spec. 18:27-30 ("It has now been found by the inventors that compositions
comprising at least two SF As ... can exhibit surprisingly enhanced
spreading behavior compared to SF As alone or SF As in combination with
non-fluorinated or fluorinated organic solvents."), 19:9-14 ("[C]ompositions
comprising at least [ two different SF As per formulas provided] have
moreover increased stability than compared to those formed by a single SF A
alone.").
state:
In another variation of their unexpected results argument, Appellants
Appellant's clinical trial results demonstrate the unique ability of
a liquid eye drop treatment consisting only of SPA F6H8 to
effectively improve the functioning of Meibomian glands in
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patients with MGD (See Messmer, et al., Semifluorierte Alkane
als Therapie bei Meibomdrusen-Dysfunktion Ergebnisse einer
prospektiven, multizentrischen Beobachtungsstudie
[Semifluorinated Alkanes as a Therapy for Meibomian Gland
Dysfunction Result of a prospective, multi-centered
observational study]) ( submitted in a previous IDS along with an
English translation [on January 16, 2017]). This data
demonstrated that for the 61 patients tested ( 122 eyes), there was
a significant improvement in both meibum quality and in
meibum quantity resulting from treatment with F6H8 eye drops.
Nothing in the cited prior art would have suggested such efficacy
for administration of an eye drop comprising only the SF A F6H8,
in the absence of any other treatment agent.
Appeal Br. 20. Through this argument, Appellants have shown neither that
the observed positive results would have been unexpected at the time of the
claimed invention nor a proper frame of reference for doing so, i.e., the
efficacy of the closest prior art.
Appellants' unexpected results arguments are not probative of non-
obviousness. Further, even if the use of F6H8 did exhibit a significant
improvement relative to other treatments in the art, the evidence of
obviousness here is strong and outweighs Appellants' rebuttal evidence.
See, e.g., Pfizer Inc. v. Apotex Inc., 480 F.3d 1348, 1372 (Fed. Cir. 2007)
("[E]ven if Pfizer showed that amlodipine besylate exhibits unexpectedly
superior results, this secondary consideration does not overcome the strong
showing of obviousness in this case. Although secondary considerations
must be taken into account, they do not necessarily control the obviousness
conclusion."). This is so because the prior art of record specifically
identifies F6H8 as one of only three "most preferred" SF As for compositions
for the treatment of dry eye. See Gunther, [57] ("The invention provides
novel pharmaceutical compositions for the treatment of keratoconjunctivitis
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sicca based on semifluorinated alkanes which are useful as carriers for a
broad range of active ingredients."), ,I44 ("Preferred SF A's include in
particular the compounds F4H5, F4H6, F6H4, F6Hb, F6H8, and F6H10.
Presently most preferred for carrying out the invention are F4H5, F6H6 and
F6H8." (emphasis added)).
For the foregoing reasons, we affirm the rejection of claims 16-18,
22, and 24 under 35 U.S.C. § 103(a) over Blackie, Gunther, admitted prior
art, Troiano, and Meinert.
Rejection 5
The Examiner rejected claims 25 and 28-30 under 35 U.S.C. § 103(a)
over Blackie, Gunther, admitted prior art, Troiano, and Meinert. Final Act.
22. For this rejection, Appellants rely on the same arguments they present
for Rejection 4 (see Appeal Br. 23-24), which rejection we affirm above.
Thus, we also affirm this rejection.
CONCLUSION
For the reasons discussed, we affirm all of the Examiner's rejections.
TIME PERIOD
No time period for taking any subsequent action in connection with
this appeal may be extended under 37 C.F.R. § 1.136(a)(l )(iv).
AFFIRMED
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