Ex Parte Byun et al

Board of Patent Appeals and Interferences

Jul 14, 2010

10851477 (B.P.A.I. Jul. 14, 2010)

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.
10/851,477 05/21/2004 Youngro Byun T10379 8739
20450 7590 07/14/2010
ALAN J. HOWARTH
P.O. BOX 1909
SANDY, UT 84091-1909
EXAMINER
HELM, CARALYNNE E
ART UNIT PAPER NUMBER
1615
MAIL DATE DELIVERY MODE
07/14/2010 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 BOARD OF PATENT APPEALS
AND INTERFERENCES
____________

Ex parte YOUNGRO BYUN and SEULKI LEE
____________

Appeal 2010-002506
Application 10/851,477
Technology Center 1600
____________

Before DONALD E. ADAMS, DEMETRA J. MILLS, and
STEPHEN WALSH, Administrative Patent Judges.

ADAMS, Administrative Patent Judge.

DECISION ON APPEAL1

This appeal under 35 U.S.C. § 134 involves claims 1-3, 19, 21-24, 27,
28, 44, 45, 47-50, 66, and 67. We have jurisdiction under 35 U.S.C. § 6(b).

1 The two-month time period for filing an appeal or commencing a civil
action, as recited in 37 C.F.R. § 1.304, or for filing a request for rehearing,
as recited in 37 C.F.R. § 41.52, begins to run from the “MAIL DATE”
(paper delivery mode) or the “NOTIFICATION DATE” (electronic delivery
mode) shown on the PTOL-90A cover letter attached to this decision.
Appeal 2010-002506
Application 10/851,477

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STATEMENT OF THE CASE
The claims are directed to a delivery agent for delivery of a
biologically active agent to a warm-blooded animal (claims 1-3 and 19); a
composition comprising a mixture of a biologically active agent and a
delivery agent (claims 21-24, 27, 28, 44, 45, 47-50, 66, and 67). In response
to a restriction requirement the following claim elements are interpreted as
follows: the active agent is insulin, the hydrophobic moiety is deoxycholic
acid and the hydrophilic moiety is L-lysine2. Claims 1 and 21 are
representative and are reproduced in the “Claims Appendix” of Appellants’
Brief (App. Br. 28 and 29).
The following rejections are under review:
1. Claims 1-3 and 19 stand rejected under 35 U.S.C § 103(a) as
unpatentable over Ayra3.
2. Claims 21-24, 27, 28, 44, 47, 49, 50, 66, and 67 stand rejected under 35
U.S.C § 103(a) as unpatentable over the combination of Ayra and Bowe4.
3. Claims 21, 45, 47, and 48 stand rejected under 35 U.S.C § 103(a) as
unpatentable over the combination of Ayra, Bowe, and The American
Heritage Dictionary5.
We affirm rejection 1 and reverse rejections 2 and 3.

2 We limit our review of the record to the elected species of the claimed
invention.
3 Ayra et al., US 5,541,348, issued July 30, 1996.
4 Caryn Lang Bowe, et al., Design of compounds that increase the
absorption of polar molecules, 94 Proc. Natl. Acad. Sci. USA 12218-12223
(1997).
5 The American Heritage Dictionary, EXCIPIENT,
http://xreferplus.com/entrypp.jsp?xrefid=7026097&secid=.-, accessed
December 13, 2007.
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Application 10/851,477

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Ayra:
ISSUE
Does the preponderance of evidence on this record support the
Examiner’s conclusion of obviousness?
FINDINGS OF FACT
FF 1. Ayra teaches “Nα-deoxycholyl-L-lysine ethylester” (Ans. 4-5 and 9-
10).
FF 2. The Examiner finds that Ayra’s Nα-deoxycholy-L-lysine ethylester
and Appellants’ claimed Nα-deoxycholy-L-lysine methylester “are homologs
of one another, differing only by the presence of an additional methyl group”
(Ans. 5).
FF 3. Ayra “teaches that bile acids were known to deliver drug molecules
into the liver and that bile salts were known to enhance intestinal absorption
of drugs that are other-wise poorly absorbed [when the drugs were
covalently linked to the bile salt] (see column 1 lines 27-34)” (Ans. 10).
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). “If a person of
ordinary skill can implement a predictable variation, § 103 likely bars its
patentability.” Id. at 417.
When identifying a reason for modifying a prior art compound under
KSR, “‘it is sufficient to show that the claimed and prior art compounds
possess a ‘sufficiently close relationship . . . to create an expectation,’ in
light of the totality of the prior art, that the new compound will have ‘similar
properties’ to the old.’” Eisai Co. Ltd. v. Dr. Reddy’s Labs., Ltd., 533 F.3d
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Application 10/851,477

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1353, 1357 (Fed. Cir. 2008) (quoting Aventis Pharma Deutschland GmbH v.
Lupin, Ltd., 499 F.3d 1293, 1301 (Fed. Cir. 2007) (quoting In re Dillon, 919
F.2d 688, 692 (Fed. Cir. 1990))).
Structural relationships may provide the requisite motivation or
suggestion to modify known compounds to obtain new
compounds. For example, a prior art compound may suggest its
homologs because homologs often have similar properties and
therefore chemists of ordinary skill would ordinarily
contemplate making them to try to obtain compounds with
improved properties. Similarly, a known compound may
suggest its analogs or isomers, either geometric isomers (cis v.
trans) or position isomers (e.g., ortho v. para).

In re Deuel, 51 F.3d 1552, 1558 (Fed. Cir. 1995). For example, in Shetty the
examiner noted that the claimed compound differed from the prior art
compound by “a mere methylene group ... and concluded that ‘this minor
molecular modification would clearly be obvious to the pharmaceutical
chemist.’” In re Shetty, 566 F.2d 81, 85-86 (CCPA 1977). The Shetty court
agreed with the examiner’s position, finding “that a person skilled in
chemical and/or pharmaceutical arts would not hesitate to extend the
alkylene linkage of the prior art compound.” Id. at 86. Similarly, as set
forth in Payne:
An obviousness rejection based on similarity in chemical
structure and function entails the motivation of one skilled in
the art to make a claimed compound, in the expectation that
compounds similar in structure will have similar properties. . . .
When prior art compounds essentially “bracketing” the claimed
compounds in structural similarity are all known as pesticides,
one of ordinary skill in the art would clearly be motivated to
make those claimed compounds in searching for new pesticides.

In re Payne, 606 F.2d 303, 313-14 (CCPA 1979) (internal citations omitted).
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“An intended use or purpose usually will not limit the scope of the
claim because such statements usually do no more than define a context in
which the invention operates.” Boehringer Ingelheim Vetmedica, Inc. v.
Schering-Plough Corp., 320 F.3d 1339, 1345 (Fed. Cir. 2003).
ANALYSIS
Nothwithstanding Appellants’ contention to the contrary (App. Br.
15), Ayra teaches “Nα-deoxycholyl-L-lysine ethylester” (FF 1). Appellants
contend that “there is no ‘adequate support in the prior art’ for the change in
structure from the lead compound to the claimed compound” (App. Br. 15-
16). We are not persuaded. Instead we agree with the Examiner’s finding
that Ayra’s Nα-deoxycholy-L-lysine ethylester and Appellants’ claimed Nα-
deoxycholy-L-lysine methylester “are homologs of one another, differing
only by the presence of an additional methyl group” (FF 2). Thus, Ayra
suggests Nα-deoxycholy-L-lysine methylester (Ans. 5; see Deuel, 51 F.3d at
1558; Shetty, 566 F.2d at 85-86; Payne, 606 F.2d at 313-14; and Eisai, 533
F.3d at 1357.
Appellants contend that “Ayra fails to disclose a delivery agent for
delivery of insulin (i.e., the elected species of active agent)” (App. Br. 16).
We are not persuaded. The preamble of claim 1 simply states the intended
use of the delivery agent (see Claim 1). Specifically, the preamble of claim
1 states that the delivery agent is intended to be used “for delivery of a
biologically active agent [(i.e. insulin)] to a warm-blooded animal” (id.).
Accordingly, we do find that the preamble of claim 1 does not limit the
scope of the delivery agent.
Ayra “teaches that bile acids were known to deliver drug molecules
into the liver and that bile salts were known to enhance intestinal absorption
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of drugs that are other-wise poorly absorbed [when the drugs were
covalently linked to the bile salt]” (FF 3). Therefore, Ayra suggests Nα-
deoxycholy-L-lysine methylester as a delivery agent for biologically active
agents (i.e., drug molecules).
For the foregoing reasons we disagree with Appellants’ contention
that the Examiner utilized “improper hindsight reasoning” (App. Br. 17-19).
CONCLUSION OF LAW
The preponderance of evidence on this record supports the
Examiner’s conclusion of obviousness. The rejection of claim 1 under 35
U.S.C § 103(a) as unpatentable over Ayra is affirmed. Since they are not
separately argued claims 2, 3, and 19 fall together with claim 1. 37 C.F.R.
§ 41.37(c)(1)(vii).

Ayra and Bowe:
ISSUE

Does the preponderance of evidence on this record support the
Examiner’s conclusion of obviousness?
FINDINGS OF FACT
FF 4. Bowe teaches a “mixture of bile salt compound and drug [i.e.
insulin] for transmucosal delivery (see page 12219[,] column 1[,] paragraph
1 – Insulin assay; page 12220[,] column 2[,] paragraph 1 – Selection of
promising transport agents” (id.).
FF 5. Bowe combined a “salt of deoxycholic acid . . . with insulin to
produce a standard for enhanced insulin absorption across a mucous
membrane” (Ans. 6).
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FF 6. Bowe found “that the distinct characteristics of the most successful
compounds were esterification of the carboxylic acid of the parent [bile acid]
molecule, and in the case of the most potent compound, the presence of an
amine (see Bowe et al. page 12220[,] column 2[,] lines 4-7 and Figure 1[,]
compounds 6 and 9)” (Ans. 7).
FF 7. The Examiner finds that “[t]he Nα-deoxycholyl-L-lysine methylester
compound made obvious by Ayra et al. is a bile acid whose carboxylic acid
group has been esterified and that also contains a positive charge due to its
amine” (Ans. 7 (emphasis added)).
FF 8. Bowe teaches that “the presence of the [C3] amine improves the
transport efficacy, although it is not clear how . . . and suggests that it is
worth investigating whether positively charged groups are useful features to
include in the design of other absorption promoters” (Bowe 12223: col. 1, ll.
26-32).
FF 9. Bowe concludes that “[m]ore work is necessary to understand the
complex relationship between the physicochemical properties of the
glycosylated steroids and their efficacy as transport agents” (Bowe 12223:
col. 1, ll. 2-4).
PRINCIPLES OF LAW
A finding of obviousness would not obtain where “what was
‘obvious to try’ was to explore a new technology or general
approach that seemed to be a promising field of
experimentation, where the prior art gave only general guidance
as to the particular form of the claimed invention or how to
achieve it.” O’Farrell, 853 F.2d at 903. This expresses the
same idea as the KSR requirement that the identified solutions
be “predictable.” 550 U.S. at 421, 127 S. Ct. 1727; see also
Procter & Gamble, 566 F.3d at 996-97; Kubin, 561 F.3d at
1359-60.
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Bayer Schering Pharma AG v. Barr Labs., Inc., 575 F.3d 1341, 1347 (Fed.
Cir. 2009).
ANALYSIS
Appellants contend that the distinct characteristics or “‘key elements’
[identified by the Examiner] of the most successful compound produced and
used by Bowe . . . [are] a positive charge due to a (C3) amine and an
esterified carboxylic acid group” (App. Br. 22). “The instantly claimed
invention does not have a positive charge at C3” (App. Br. 23). In addition,
Appellants contend that “[i]t is also possible that [in Bowe] the positive
charge at C3 must be accompanied by glucose residues being present at C7
and C12 to achieve the results obtained, since compounds lacking glucose
residues at C7 and C12 were not tested by Bowe” (App. Br. 23). “The
instantly claimed invention does not have glucose residues at C7 and C12”
(id.).
Notwithstanding the foregoing differences between the bile acid
compound of Bowe and Ayra; and the distinct mechanism of drug delivery
(i.e. Ayra’s covalently linked drug and bile acid vs. Bowe’s mixture of bile
acid and drug (FF 3 and 4)), the Examiner asserts that “[i]n light of . . . the
similarity in properties between the best transport enhancers in Bowe et al.
and the Nα-deoxycholyl-L-lysine methylester made obvious by Ayra et al.
one of ordinary skill in the art would have had a reasonable expectation that
the compound of Ayra et al. would function as a transmucosal absorption
enhancer” (Ans. 13 (emphasis added)). We disagree.
The Examiner recognizes that Ayra teaches the covalent attachment of
the drug to the bile acid to facilitate transport, while Bowe’s transport
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mechanism does not require a covalent attachment of the drug to the bile
acid (FF 3 and 4). As discussed above, Appellants have identified structural
differences between the bile acids taught by Ayra and Bowe. With regard to
the C3 amine, Bowe teaches that further investigation is necessary to
determine the effect of a positive charge on the design of absorption
promoters (e.g., bile acids) (FF 8). All of this dovetails with Bowe’s
teaching that “[m]ore work is necessary to understand the complex
relationship between the physicochemical properties of the glycosylated
steroids and their efficacy as transport agents” (FF 9), and supports a
conclusion that the combination of Ayra and Bowe provides a general
approach in a promising, yet unpredictable, field of experimentation. Bayer
Schering Pharma AG v. Barr Labs., Inc., 575 F.3d at 1347.
CONCLUSION OF LAW
The preponderance of evidence on this record fails to support the
Examiner’s conclusion of obviousness. The rejection of claims 21-24, 27,
28, 44, 47, 49, 50, 66, and 67 under 35 U.S.C § 103(a) as unpatentable over
the combination of Ayra and Bowe is reversed.

Ayra, Bowe, and The American Heritage Dictionary:
ISSUE

Does the preponderance of evidence on this record support the
Examiner’s conclusion of obviousness?
FINDINGS OF FACT
FF 10. Ayra and Bowe are relied upon as discussed above (see generally
Ans. 9).
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FF 11. The Examiner relies on The American Heritage Dictionary for the
definition of the term “excipient” (id.).
ANALYSIS
Appellants contend that The American Heritage Dictionary fails to
make up for the deficiency in the combination of Ayra and Bowe (see App.
Br. 25). We agree.
CONCLUSION OF LAW
The preponderance of evidence on this record fails to support the
Examiner’s conclusion of obviousness. The rejection of claims 21, 45, 47,
and 48 under 35 U.S.C § 103(a) as unpatentable over the combination of
Ayra, Bowe, and The American Heritage Dictionary is reversed.
TIME PERIOD FOR RESPONSE
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-IN-PART

alw

ALAN J. HOWARTH
P.O. BOX 1909
SANDY, UT 84091-1909