Ex Parte Doney

Patent Trial and Appeal Board

Oct 15, 2015

11496030 (P.T.A.B. Oct. 15, 2015)

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.
11/496,030 07/28/2006 John Alfred Doney 2970 2656
7590 10/16/2015
International Specialty Products
Attn: William J. Davis, Esq.
Legal Department, Bldg. 8
1361 Alps Road
Wayne, NJ 07470
EXAMINER
ALSTRUM ACEVEDO, JAMES HENRY
ART UNIT PAPER NUMBER
1675
MAIL DATE DELIVERY MODE
10/16/2015 PAPER
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.
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
__________

BEFORE THE PATENT TRIAL AND APPEAL BOARD
__________

Ex parte JOHN ALFRED DONEY
__________

Appeal 2013-001390
Application 11/496,030
Technology Center 1600
__________

Before JEFFREY N. FREDMAN, ULRIKE W. JENKS, and
JACQUELINE T. HARLOW, Administrative Patent Judges.

FREDMAN, Administrative Patent Judge.

DECISION ON APPEAL
This is an appeal1 under 35 U.S.C. § 134 involving claims to a
composition comprising efavirenz and a solubility-enhancing polymer. The
Examiner rejected the claims as obvious. We have jurisdiction under
35 U.S.C. § 6(b). We affirm.

Statement of the Case
Background
“Efavirenz is . . . a benzoxazinone useful as a nonnucleoside inhibitor
of HIV-1 reverse transcriptase” (Spec. ¶ 2). “It is desirable to provide
methods of producing efavirenz exhibiting enhanced bioavailability
compared to the crystalline form of the compound. By converting a

1 Appellant identifies the Real Party in Interest as ISP Investments Inc. (see
App. Br. 3).
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substantial portion of crystalline efavirenz to the amorphous state, the
aqueous solubility and bioavailability are increased” (id. ¶ 4).
The Claims
Claims 1, 3–27, 43–45, and 57–66 are on appeal. Independent claim 1
is representative and reads as follows:
1. A composition comprising efavirenz and a solubility-
enhancing polymer in the form of a solid solution wherein said
efavirenz is more than 75% amorphous and exhibits enhanced
bioavailability compared to a control composition without the
solubility-enhancing polymer.

The Issues
A. The Examiner rejected claims 1, 3–13, 22–25, 27, 43–452, and 57–66
under 35 U.S.C. § 103(a) as obvious over Yuk3 and “Chemical Land”4 (Final
Rej. 3–6).
B. The Examiner rejected claims 14–21 and 26 under 35 U.S.C. § 103(a)
as obvious over Yuk, “Chemical Land” and Straub5 (Final Rej. 10–11).

2 The Examiner includes claim 43 and cancelled claim 46 in the statement of
rejection (see Final Rej. 3), identifies claims 43–45 as rejected in the Office
Action Summary Sheet mailed with the Final rejection, and identifies claims
43–45 as rejected (see Ans. 5), but inadvertently fails to include claims 44
and 45 in the statement of rejection in the Final Rejection. Appellants do not
separately argue these two claims. We therefore treat their omission as
inadvertent and harmless.
3 Yuk et al., WO 00/40220 A1, published July 13, 2000 (“Yuk”).
4 Efavirenz, http://chemicalland21.com/lifescience/UH/
EFAVIRENZ.htm (last visited March 9, 2010) (“Chemical Land”).
5 Straub et al., US 2002/0142050 A1, published Oct. 3, 2002 (“Straub”).
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A. 35 U.S.C. § 103(a) over Yuk and “Chemical Land”
The issue with respect to this rejection is: Does the evidence of
record support the Examiner’s conclusion that the spray dried composition
of Yuk and “Chemical Land” suggests “efavirenz and a solubility-enhancing
polymer in the form of a solid solution” as required by claims 1 and 43?
Findings of Fact
1. Yuk teaches a “method of preparing a pharmaceutical active
ingredient comprising a water-insoluble drug. The method includes the
steps of mixing a water-insoluble drug in an organic solvent with a water-
soluble polymer in an aqueous solvent and spray-drying the mixture” (Yuk
2, ll. 16–20).
2. Yuk teaches that a “water-insoluble drug is dissolved in an
organic solvent such as acetone to prepare a drug solution” (id. at 3, ll. 21–
22).
3. Yuk teaches that:
A water-soluble polymer is dissolved in an organic
solvent such as ethanol aqueous solution to prepare a polymer
solution. As the water-soluble polymer, cellulose type
compound may be used. The exemplary of cellulose type
compound is ethylcellulose, polyethyleneglycol,
carboxymethylcellulose, polyethyleneglycol,
polyvinylpyrollidone, dextran, poloxamer and a mixture
thereof.

(Id. at 3, l. 24 to 4, l. 5).
4. Yuk teaches that the “mixed solution and air are injected into a
spray-dryer body, while raising the ambient temperature by the heated air
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and mixed solution is changed from solution form to microparticle form by
heated air” (id. at 4, ll. 16–19).
5. Example 1 of Yuk teaches:
1 part by weight of ipriflavone was dissolved in 8 parts by
weight of acetone to prepare a water-insoluble drug solution. 2
parts by weight of hydroxypropylmethylcellulose was dissolved
in an aqueous ethanol solution including 1 part by weight of
water and 1 part by weight of ethanol to prepare a water-soluble
polymer solution. 4 parts by weight of the polymer solution
was added to 9 parts by weight of the drug solution and mixed
well by using a homogenizer. The mixed solution was spray-
dried at 50°C for 20 minutes by using a spray-dryer shown in
Fig.2 to obtain the water-insoluble drug microparticles
combined with water-soluble polymer.

(Id. at 5, ll. 14–22).
6. “Chemical Land” teaches that “Efavirenz is a non-nucleoside
reverse transcriptase inhibitor of HIV-1 (human immunodeficiency virus-1).
It is a white to off-white crystalline powder; insoluble in water, soluble in
lower alcohol (methanol)” (“Chemical Land” 1).
7. The Specification teaches that in “one aspect, the disclosed
invention describes the conversion of crystalline efavirenz to the amorphous
state. One method for producing this conversion is through solvent spray
drying” (Spec. ¶ 5).
8. Examples 1, 3, 5, 7, and 8 of the Specification disclose different
preparation conditions in which efavirenz was spray dried, with every
condition resulting in a completely amorphous powder (see Spec. ¶ 71).
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9. The Specification teaches that the “term ‘solid solution’ as used
herein refers to a type of solid dispersion wherein one component is
molecularly dispersed throughout another component” (id. ¶ 24).
Principles of Law
“The combination of familiar elements according to known methods
is likely to be obvious when it does no more than yield predictable results.”
KSR Int’l Co. v. Teleflex Inc., 550 U.S. 398, 416 (2007).
Where, as here, the claimed and prior art products are identical
or substantially identical, or are produced by identical or
substantially identical processes, the PTO can require an
applicant to prove that the prior art products do not necessarily
or inherently possess the characteristics of his claimed product.
. . . Whether the rejection is based on ‘inherency’ under
35 U.S.C. § 102, on ‘prima facie obviousness’ under 35 U.S.C.
§ 103, jointly or alternatively, the burden of proof is the same,
and its fairness is evidenced by the PTO’s inability to
manufacture products or to obtain and compare prior art
products.

In re Best, 562 F.2d 1252, 1255 (CCPA 1977).
Analysis
We adopt the Examiner’s findings of fact and reasoning regarding the
scope and content of the prior art (Final Rej. 3–6; FF 1–8) and agree that the
claims would have been obvious over the teachings of Yuk and “Chemical
Land.” We address Appellants’ arguments below.
Claims 1 and 43
Appellants contend that “Yuk fails to disclose or suggest a solid
solution as set forth in the pending claims” (App. Br. 7). Appellants contend
that the “Yuk process results in microparticles of the active combined with
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the water-soluble polymer, which is not consistent with a solid solution” (id.
at 7–8). Appellants contend that “it is well known in the art that products
produced by spray drying can be in a variety of forms and exhibit a wide
range of properties” (id. at 9). Appellants cite Killeen,6 who states that
“[h]owever, other properties like porosity, loose and tapped densities,
moisture, and friability are influenced by the dryer’s design and operations.
By combining various spray techniques and drying parameters, a wide range
of physical properties are possible for a given substance” (Killeen 57,
col. 2).
We are not persuaded. Yuk teaches a process involving combining a
homogenous mixture of a drug compound and a solubility-enhancing
polymer, each dissolved in solutions miscible with one another and
subjected to spray drying to produce drug microparticles (FF 5). This
process falls within the scope required by claim 43, which also teaches
formation of particles. The Specification teaches that spray drying converts
efavirenz to the amorphous state (FF 7) and results in a solid solution (FF 8–
9)
We therefore conclude that the Examiner has established a prima facie
case that the obvious combination of efavirenz and a solubility enhancer
when formulated using the spray drying method of Yuk inherently results in
a solid dispersion. Having established a prima facie case of obviousness, the
Examiner properly shifted the burden of proof to Appellants. Best, 562 F.2d
at 1255. The sole rebuttal evidence proffered by Appellants is Killeen’s

6 Killeen, M., The Process of Spray Drying and Spray Congealing, 13
Pharm. Engineering 56–64 (1993).
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statement that a variety of physical properties are possible for a given
substance. However, that statement does not fairly address the similarity of
Yuk’s process and products to those claimed. Yuk provides specific
guidance with specific spray techniques, drying parameters, and solvents (FF
1–5) that result in a solid microparticle composed of a water-insoluble drug
and water-soluble polymer (FF 5).
As we balance the generic teaching of Killeen against the specific
spray drying process of Yuk, we conclude that Appellants have failed to
provide sufficiently specific evidence rebutting the Examiner’s finding that
the process of Yuk would inherently have formed a solid solution as
required by the claims.
Appellants contend that “Yuk starts with two separate solutions: a
drug solution in an organic solvent and a water-soluble polymer solution in
an ethanol aqueous solution. The two solutions are only mixed just prior to
spray drying and there is no indication that the components are solubilized in
the mixture” (App. Br. 9–10).
We are not persuaded. Yuk teaches that the drug “ipriflavone was
dissolved in . . . acetone to prepare a water-insoluble drug solution” and that
“hydroxypropylmethylcellulose was dissolved in aqueous ethanol solution
. . . to prepare a water-soluble polymer solution” (FF 5). As the Examiner
correctly notes “ethanol, water, and acetone solvents are all mutually
miscible” (Ans. 6), and the Examiner further points out that Yuk does not
suggest that upon mixing the two solutions “anything precipitates or that any
phase separation occurs” (id.). Thus, we agree with the Examiner that the
ordinary artisan would reasonable understand Yuk to teach a homogenous
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solution because the “mixture of the two solutions yields a solution as well”
and the resulting solution is a homogenous dispersal of the components prior
to spray drying (see Ans. 6.).
Appellants contend that “[b]ecause of the uncertainty associated with
different drugs and how they will respond in any particular formulation,
there is not the expectation of success that is required for a prima facie case
of obviousness” (App. Br. 10).
We are not persuaded. In “[r]esponding to concerns about uncertainty
in the prior art influencing the purported success of the claimed
combination,” the Federal Circuit has stated: “‘[o]bviousness does not
require absolute predictability of success . . . all that is required is a
reasonable expectation of success.”’ In re Kubin, 561 F.3d 1351, 1360 (Fed.
Cir. 2009) (emphasis omitted) (citing In re O’Farrell, 853 F.2d 894, 903–
904 (Fed. Cir. 1988)). Yuk teaches the preparation of water-insoluble drugs
by spray drying generically (FF 1) and teaches the preparation of a particular
water-insoluble drug specifically (FF 5). In contrast, Appellants provide no
evidence of any uncertainty in applying the method of Yuk to other known
water-insoluble drugs such as efavirenz (FF 6). See In re Pearson, 494 F.2d
1399, 1405 (CCPA 1974) (“Attorney’s argument in a brief cannot take the
place of evidence.”). We therefore conclude that the facts support the
conclusion that there would have been a reasonable expectation of success in
preparing the water-insoluble drug efavirenz by the spray drying method
suggested by Yuk for water-insoluble drugs (FF 1–6).
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Claims 63–66
Appellants contend that “application contains specific reference to the
improved properties that are associated with particular combinations. For
example, item 3 under Example 8 describes some of the unexpected benefits
associated with the solvent/non-solvent blends” (App. Br. 10).
We do not find this argument persuasive because Yuk teaches spray
drying in a mixture of hydroxypropylmethylcellulose/acetone/ethanol/water,
which blends solvent and non-solvent as required by claim 63. In addition,
we agree with the Examiner that to the extent that the Specification recites
an unexpected result, the result is not commensurate in scope with the
claims. Claim 63 is open to the use of any solubility-enhancing polymer and
any solvent, while Example 8 of the Specification is limited to PVP as the
solubility enhancing polymer, dicholoromethane as the solvent with acetone
as the non-solvent (see Spec. ¶ 71). “[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 re Baxter Travenol Labs., 952 F.2d
388, 392 (Fed. Cir. 1991). Also see In re Harris, 409 F.3d 1339, 1344 (Fed.
Cir. 2005) (“The Board also correctly reasoned that the showing of
unexpected results is not commensurate in scope with the degree of
protection sought by the claimed subject matter”).
Conclusion of Law
The evidence of record supports the Examiner’s conclusion that the
spray dried composition of Yuk and “Chemical Land” suggests “efavirenz
and a solubility-enhancing polymer in the form of a solid solution” as
required by claims 1 and 43.
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B. 35 U.S.C. § 103(a) over Yuk, “Chemical Land,” and Straub
Appellants do not argue separately the claims in this obviousness
rejection. Having affirmed the obviousness rejection over Yuk and
“Chemical Land” for the reasons given above, we also find that the further
obvious combination with Straub render the remaining claims obvious for
the reasons given by the Examiner (see Final Rej. 10–11).
SUMMARY
In summary, we affirm the rejection of claims 1, 43, and 63–66 under
35 U.S.C. § 103(a) as obvious over Yuk and “Chemical Land”. Claims 3–
13, 22–25, 27, 44–45, and 57–62 fall with claims 1, 43, and 63–66.
We affirm the rejection of claims 14–21 and 26 under 35 U.S.C.
§ 103(a) as obvious over Yuk, “Chemical Land,” and Straub.
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

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