Sami Nazzal et al.

Patent Trials and Appeals Board

Aug 5, 2020

13656573 - (D) (P.T.A.B. Aug. 5, 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.
13/656,573 10/19/2012 Sami Mahmoud Nazzal 011.08 4963
107354 7590 08/05/2020
Edel Patents LLC
8550 United Plaza Blvd., Suite 702
Baton Rouge, LA 70809
EXAMINER
BASQUILL, SEAN M
ART UNIT PAPER NUMBER
1613
NOTIFICATION DATE DELIVERY MODE
08/05/2020 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):
john@edelpatents.com
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
__________

BEFORE THE PATENT TRIAL AND APPEAL BOARD
__________

Ex parte SAMI MAHMOUD NAZZAL,
PAUL W. SYLVESTER, and ALAADIN Y. ALAYOUBI
__________

Appeal 2019-006322
Application 13/656,573
Technology Center 1600
__________

Before JEFFREY N. FREDMAN, ROBERT A. POLLOCK, and
RACHEL H. TOWNSEND, Administrative Patent Judges.

FREDMAN, Administrative Patent Judge.

DECISION ON APPEAL
This is an appeal1 under 35 U.S.C. § 134 involving claims to vitamin
E compositions. The Examiner rejected the claims as obvious. We have
jurisdiction under 35 U.S.C. § 6(b). We reverse.

Statement of the Case
Background
“Vitamin E is a group of compounds having eight members . . . .
Compounds and formulations disclosed herein have potential use as
pharmaceutical products and may be employed in the treatment of various

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 First Tech
International Limited (see Appeal Br. 3).
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maladies including cancer and may specifically have uses in the treatment of
breast, colon and other related cancers” (Spec. ¶ 2).
The Claims
Claims 56–65 and 67–76 are on appeal. Independent claims 56 and
76 are representative and read as follows:
56. A composition of matter comprising:
a. a quantity of vitamin E;
b. a glycerol ester; and
c. a polyoxyethylated triglyceride;
d. wherein the composition of matter is sufficiently
homogenized to perform as a self-emulsifying drug delivery
system;
e. wherein the quantity of vitamin E is at least 15 weight
percent of the composition of matter; and
f. wherein the quantity of vitamin E is at most 55 weight
percent of the composition of matter.
g. wherein the composition of matter is configured such that it
completely emulsifies upon dissolution in water; and
h. wherein the composition of matter is sufficiently
homogenized to create an aqueous emulsion having an
intensity-weighed mean droplet size of less than 700 nm upon
dissolution in water.

76. A composition of matter consisting essentially of:
a. 50 weight percent vitamin E;
b. 29.5 weight percent polyoxyethylated triglyceride; and
c. 20.5 weight percent glycerol ester;
d. wherein the composition of matter is sufficiently
homogenized to perform as a self-emulsifying drug delivery
system;
e. wherein the composition of matter is configured such that it
completely emulsifies upon dissolution in water; and
f. wherein the composition of matter is sufficiently
homogenized to create an aqueous emulsion having an
intensity-weighed mean droplet size of less than 700 nm upon
dissolution in water.
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Among the claims depending from claim 56, claim 59 further defines
the composition to include ethanol, claims 62, 63, and 65, further define the
composition as including a triglyceride of caprylic or capric acid; claims 58
and 60 recite that the polyoxyethylated triglyceride is polyoxyethylated
castor oil; and claims 61 and 65 recite that “the majority of the quantity of
vitamin E is tocotrienol.”

The Issue
The Examiner rejected claims 56–65 and 67–76 under 35 U.S.C.
§ 103(a) as obvious over Ho2 and Lipari3 (Ans. 3–9).
The Examiner finds “Ho describes self-emulsifying formulations
(SEDDS) containing fat-soluble (ergo lipophilic or sparingly soluble in
water) drugs which form emulsions upon contact with gastrointestinal
fluids” (Ans. 6). The Examiner finds Ho teaches “TOCOMIN tocotrienols
in 25%, each of either palm olein or soybean oil at 58.6%, LABRASOL at
14.5%, and TWEEN 80 at 2.2% of the composition” (id.). The Examiner
finds that based on Ho, the “artisan can at once envisage the use of
tricaprylin caprylic/capric triglycerides in place of the other two particularly
embodied oily vehicles that comprise the total list of suitable alternatives”
(id. at 7).
The Examiner acknowledges “Ho does not recite the use of
polyethoxylated castor oil, ethanol, a glycerol ester, or the precise
triglyceride or tocotrienol concentrations claimed recited” (Ans. 6).

2 Ho et al., US 6,596,306 B1, issued July 22, 2003.
3 Lipari et al., US 2007/0104780 A1, published May 10, 2007.
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The Examiner finds Lipari teaches “that a combination of
phospholipid, solubilizing agent, and surfactant system each combine to
improve the solubilization of the sparingly soluble drug to be delivered”
(Ans. 7). The Examiner finds Libari teaches “capric and caprylic acid
triglycerides exemplified by CAPTEC 355”; “ethanol” and polyoxy 35
castor oil such as CREMOPHOR EL” (id. at 7–8).
The Examiner finds Ho and Lipari teach the component
concentrations are “very important for establishing enhanced drug
absorption and self-emulsifying properties” (Ans. 8). The Examiner finds it
obvious
to have incorporated any, or indeed all, of the phospholipid,
ethanol, or polyoxy castor oil taught by Lipari as either
alternative surfactants, solubilizers, or adjuvants designed to
improve a SEDDS for the delivery of sparingly soluble
therapeutic active agents into the SEDDS taught by Ho as
SEDDS [are] useful for forming finely divided emulsions for
delivering the tocotrienol lipophilic active agent.

(Id. at 9).
The issues with respect to this rejection are:
(i) Does a preponderance of the evidence of record support the
Examiner’s conclusion that Ho and Lipari render the claims obvious?
(ii) If so, has Appellant provided evidence of unexpected results that
outweighs the evidence supporting the prima facie case of obviousness?
Findings of Fact
1. Ho teaches a “pharmaceutical formulation for oral
administration which comprises: (i) a fat-soluble drug; (ii) an appropriate
oil; and (iii) an appropriate surfactant system; the resulting formulation
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which self-emulsifies under gentle agitation in the presence of an aqueous
medium” (Ho 2:46–52).
2. Ho teaches a “formulation of tocotrienols, in which the
tocotrienols are incorporated into a palm olein-surfactant system to form a
self-emulsifying system” (Ho 2:54–56).
3. Ho teaches
different surfactant systems at various ratio were tried out to get
a self-emulsifying drug delivery system (SEDDS). The aim of
this part of the study is to incorporate tocotrienols into a
suitable surfactant system that will cause the preparation
(tocotrienols in oil vehicles) to self-emulsify/form an emulsion
easily with gentle agitation

(Ho 3:64 to 4:3).
4. Ho teaches a table of the final formulation reproduced below:

(Ho 4:31–38).
5. Claim 1 of Ho teaches, in part, a
self-emulsifying drug delivery composition for use with oral
administration of fat-soluble drugs, said composition consisting
essentially of: a fat-soluble drug selected from the group
consisting of tocotrienols, tocopherols . . . an oil selected from
the group consisting of palm olein and soy bean oil . . . a
surfactant system comprised of a first component consisting of
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caprylocaproyl macrogolglycerides and a second component
consisting of polyoxyethylene sorbitan monooleate

(Ho 6:26–38).
6. Claim 3 of Ho teaches, in part, the “composition of claim 1,
wherein the fat-soluble drug is about 24.8 weight percent of the
composition” (Ho 6:46–47).
7. Ho teaches
the studies had optimized three important formulation
variables to achieve a superior product with enhanced
bioavailability/absorption, namely
(i) use of palm olein and soybean oil as the vehicle for
fat-soluble drugs like tocotrienols, which help to enhance
absorption;
(ii) addition of a suitable combination of Labrasol and
Tween 80 into the drug/oil mixture to promote self-
emulsification and thus help to further increase the absorption
of tocotrienols; and
(iii) a suitable combination of surfactant system
(Labrasol and Tween 80) with the oil/drug mixture to optimize
drug absorption.

(Ho 2:28–40).
8. Lipari teaches “a drug-carrier system having a small-molecule
drug of low water solubility in solution in a substantially non-aqueous
carrier that comprises (a) at least one phospholipid and (b) a
pharmaceutically acceptable solubilizing agent. The drug-carrier system,
when mixed with an aqueous phase, forms a non-gelling, substantially non-
transparent liquid dispersion” (Lipari ¶ 15).
9. Lipari teaches
the carrier comprises two essential components: at least one
phospholipid, and a pharmaceutically acceptable solubilizing
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agent for the at least one phospholipid. The solubilizing agent,
or the combination of solubilizing agent and phospholipid, also
solubilizes the drug, although other carrier ingredients such as a
surfactant optionally present in the carrier can in some
circumstances provide enhanced solubilization of the drug.

(Lipari ¶ 79).
10. Lipari teaches in “one embodiment, the solubilizing agent
comprises . . . one or more glyceride materials” (Lipari ¶ 82).
11. Lipari teaches a “suitable example of a medium chain
triglyceride material is a caprylic/capric triglyceride product such as, for
example, Captex 355 EP” (Lipari ¶ 86) (see Spec. ¶ 42 “triglycerides of
caprylic/capric acid sold as Captex® 355 and referred to herein as ‘Captex’
and C8/C10 polyglycolyzed glycerides from coconut oil sold as Labrasol®
referred to herein as ‘Labrasol’ were provided by BASF.”)
12. Lipari teaches a
suitable total amount of glycerides is an amount effective to
solubilize the phospholipid and, in combination with other
components of the carrier, effective to maintain the drug in
solution. For example, glyceride materials such as medium
chain and/or long chain triglycerides can be present in a total
glyceride amount of about 5% to about 70%.

(Lipari ¶ 87).
13. Lipari teaches “to select a suitable surfactant for use in the
composition . . . a surfactant such as polysorbate 20 can be included in an
amount of 0% to about 25%” (Lipari ¶ 88).
14. Lipari teaches the use of “Cremophor EL™ of BASF: polyoxyl
castor oil” (Lipari ¶ 126) (see Spec. ¶ 41 “self-emulsifying drug delivery
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system (SEDDS) formulations described in Table 1 below were prepared
using Tween 80 or Cremophor EL as the primary surfactant”).
15. Lipari teaches
the drug must normally be formulated at a concentration below
its limit of solubility in the carrier. It will be understood that
the limit of solubility can be temperature-dependent, thus
selection of a suitable concentration should take into account
the range of temperatures to which the composition is likely to
be exposed.

(Lipari ¶ 77).
Principles of Law
“[W]here the general conditions of a claim are disclosed in the prior
art, it is not inventive to discover the optimum or workable ranges by routine
experimentation.” In re Aller, 220 F.2d 454, 456 (CCPA 1955).
Prima facie obviousness can be rebutted by presenting evidence of
secondary considerations and when such evidence is submitted, all of the
evidence must be considered anew. In re Piasecki, 745 F.2d 1468, 1472–
1473 (Fed. Cir. 1984).
Analysis
We agree with the Examiner’s conclusion that a composition with
15% vitamin E that completely emulsifies with optimized droplet sizes
would have been prima facie obvious in view of the cited references.
However, we find that Appellant’s rebuttal arguments, along with the
evidence of unexpected results has successfully overcome the prima facie
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case of obviousness.4
In our previous Decision, we noted that “claim 56 imposes no specific
percentage of vitamin E that must be dissolved” (Dec. 10). That statement is
not applicable to the claims presently on appeal, as claims 56 and 76 now
require complete emulsification of all of the vitamin E. Also, in our
previous decision, we noted that “Appellants have provided no evidence that
the 24.8 weight percent value for fat-soluble drugs taught by Ho would not
have been enabled by Ho” (Dec. 11). In the record in this appeal, however,
that statement is no longer applicable, as the Nazzal Declaration
demonstrates that Ho’s composition would not satisfy the complete
emulsification or size requirements now included in claims 56 and 76.
The Nazzal Declaration5 explains: “Two formulations were prepared
according to the ‘final master formulation’ of Ho ’306”; the self-emulsifying
properties of those formulations were assessed; finds the “average size of the
resulting emulsion from the Ho ’306 ‘final master formulation’ according to
the above procedure had an average measured value of 1565nm”; and finds
the “Ho ’306 ‘final master formulation’ did not fully emulsify and liquid oil
from the Ho ’306 ‘final master formulation’ was observed floating on top of
the resulting mixture” (Nazzal Decl. 2–3).
Thus, the Nazzal Declaration directly tests the cited prior art, Ho, and
shows that Ho does not satisfy the requirements of either claims 56 or 76.

4 We note that the rejection incorrectly applies the doctrine of res judicata
(Ans. 11), because Appellant has provided new evidence of patentability in
the Nazzal Declaration (see MPEP § 2190(II)).
5 Declaration of Sami Nazzal, dated Oct. 19, 2018. We number the pages
sequentially beginning with the “Declaration Under 37 CFR 1.132” heading.
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The Nazzal Declaration also provides analysis of other prior art
SEDDS formulations. In particular, it analyzes data from twenty-five prior
art SEDDS formulations of varying amounts of alpha-tocopherol, TWEEN
80, labrasol, captex 355, and alcohol USP presented in Ali6. (Nazzal Decl.
6–7.) The Nazzal Declaration explains that only three of these self-
emulsifying formulations in Ali satisfied the requirements of “completely
emulsifies upon dissolution” and “droplet sizes less than 700 nm” recited in
claims 56 and 76, and that those formulations only had 12.5% vitamin E,
which is less than the claimed amount required by both of claims 56 and 76.
(Nazzal Decl. 6–7; cf. Ali 106, Table 2, runs 1, 3, 19).
The Nazzal Declaration points out that every example in Ali with
amounts of vitamin E that fall within the range required by either of claims
56 or 76 failed to satisfy the requirements of “completely emulsifies upon
dissolution” and “droplet sizes less than 700 nm” (Nazzal Decl. 7; cf. Ali
106, Table 2, runs 2, 4–8, 10–13, 15, 16, 18, 20–25).
The Nazzal Declaration states “[b]ased on the facts presented above
and for the same reasons, at the time of invention, the production of a > 15%
vitamin E SEDDS capable of fully emulsifying into a sub 700 nm emulsion
was an unexpected result” (Nazzal Decl. 7).
The Examiner responds to this evidence by stating it “is to be
presumed that skilled workers would, as a matter of course, if they do not
immediately obtain desired results, make certain experiments and

6 Ali et al., Comparison between lipolysis and compendial dissolution as
alternative techniques for the in vitro characterization of α-tocopherol self-
emulsified drug delivery systems (SEDDS), 352 International J. Pharm. 104–
114 (2008).
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adaptations within the skill of the competent worker” (Ans. 12). The
Examiner also states that “Appellants’ bald assertion, absent a scintilla of
supporting evidence, suggesting that no one on Earth had managed to
formulate SEDDS incorporating vitamin E concentrations above 15% are
unpersuasive because the arguments of counsel cannot take the place of
evidence in the record” (Ans. 15).
We find that Appellant has demonstrated unexpected results on the
current record. As shown by the Nazzal Declaration, Appellant has provided
substantial evidence that prior art formulations did not achieve a formulation
containing either at least 15% vitamin E as recited in claim 56, or 50%
vitamin E as recited in claim 76, that completely emulsified upon dissolution
and resulted in droplet sizes of less than 700 nm as required (see Nazzal
Decl. 3–7). These results were comparisons of the closest prior art, either
Ho or Ali, and were commensurate in scope with the very narrow claims at
issue, which also demonstrate a difference in kind, not just degree, in that
complete emulsification differs from the incomplete emulsification shown
by the Nazzal Declaration for the Ho composition (see Nazzal Decl. 3).
Thus, the evidence of record comports with the requirements necessary to
demonstrate unexpected results.
In addition, Appellant has now satisfied the burden necessary to show
that there are enablement concerns with Ho given the failure of Ho to satisfy
the emulsification and droplet size requirements. In re Antor Media Corp.,
689 F.3d 1282, 1289 (Fed. Cir. 2012). Appellant has provided evidence that
the 12.4 weight percent of vitamin E would not satisfy the claim (see Nazzal
Decl. 3), much less the 24.8 weight percent value that would have a lesser
expectation of solubility.
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The Examiner’s statement regarding the inability of the prior art to
“formulate SEDDS incorporating vitamin E concentrations above 15%” fails
to consider all the limitations of the claims presently on appeal. While we
agree with the Examiner that SEDDS with higher vitamin E concentrations
above 15% may well be obvious, as shown in part by Ali (see Ali 106, table
2), that does not answer the question of whether compositions with vitamin
E concentrations above 15% that “completely emulsifies upon dissolution in
water” and which has a “droplet size of less than 700 nm” would have been
obvious.
To the extent that the Examiner is treating these limitations as
intended use recitations, we disagree. These functional recitations provide
for a compositional structure when a certain condition is met. A patent
applicant is free to recite features of a composition either structurally or
functionally. See, e.g., In re Schreiber, 128 F.3d 1473, 1478 (Fed. Cir.
1997); cf. MPEP § 2173.05(g) (“A functional limitation must be evaluated
and considered, just like any other limitation of the claim, for what it fairly
conveys to a person of ordinary skill in the pertinent art in the context in
which it is used. A functional limitation is often used in association with an
element, ingredient, or step of a process to define a particular capability or
purpose that is served by the recited element, ingredient or step.”)
The “completely emulsifies” and “droplet size of less than 700 nm”
recitations impose specific structural requirements on the composition of
matter that differ from compositions that do not have these recitations.
Indeed, run 2 of Ali has 25% Vitamin E, Labrasol, a polyglycolyzed
glyceride, and Captex, a triglyceride component, but run 2 neither
completely emulsifies nor results in droplet sizes of less than 700 nm upon
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dissolution in water(see Ali 106, table 2). Thus, these limitations function to
distinguish the claimed composition structurally from the run 2 composition
of Ali that does not satisfy these recitations.
Conclusion of Law
(i) A preponderance of the evidence of record support the Examiner’s
conclusion that Ho and Lipari render the claims obvious.
(ii) Appellant has provided evidence of unexpected results that
outweighs the evidence supporting the prima facie case of obviousness.

CONCLUSION
In summary:
Claims
Rejected
35 U.S.C.
§
Reference(s)/Basis Affirmed Reversed
56–65, 67–76 103 Ho, Lipari 56–65, 67–76

REVERSED