BETA INNOV

Patent Trials and Appeals Board

Jun 12, 2020

14399336 - (D) (P.T.A.B. Jun. 12, 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.
14/399,336 11/06/2014 Ludovic Clarion 0579-1330-1 9587
466 7590 06/12/2020
YOUNG & THOMPSON
209 Madison Street
Suite 500
Alexandria, VA 22314
EXAMINER
BADIO, BARBARA P
ART UNIT PAPER NUMBER
1628
NOTIFICATION DATE DELIVERY MODE
06/12/2020 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):
DocketingDept@young-thompson.com
yandtpair@firsttofile.com
PTOL-90A (Rev. 04/07)

UNITED STATES PATENT AND TRADEMARK OFFICE
____________

BEFORE THE PATENT TRIAL AND APPEAL BOARD
____________

Ex parte LUDOVIC CLARION, MARCEL MERSEL, and
DIDIER PETITE
____________

Appeal 2019-004144
Application 14/399,3361
Technology Center 1600
____________

Before JEFFREY N. FREDMAN, JOHN G. NEW, and
DAVID D. COTTA, Administrative Patent Judges.

COTTA, Administrative Patent Judge.

DECISION ON APPEAL

This is an appeal under 35 U.S.C. § 134 relating to sterol derivatives
for treating transformed astrocyte cells or for treating malignant
haemopathies. Spec. 1. The Examiner rejected the claims on appeal as
obvious under 35 U.S.C. § 103(a). A hearing was held on April 1, 2020.2
We reverse.

1 We use the word “Appellant” to refer to “applicant” as defined in
37 C.F.R. § 1.42. According to Appellant, the real party in interest is BETA
INNOV. Appeal Br. 1.
2 A transcript from the hearing has been entered into the record (“Tr.”).
Appeal 2019-004144
Application 14/399,336

2
STATEMENT OF THE CASE
The Specification discloses that “7β-Hydroxycholesterol (7β-OHCH),
a molecule with high anti-cancer potential, shows remarkable cytotoxicity
on immortalized (spontaneously transformed) rat astrocyte lines and GBMs
(rat line C6) ‘in vitro.’” Spec. 4 (internal citations omitted). The
Specification also discloses that the esterification of 7β-OHCH at C3-OH by
intracellular fatty acids, has been implicated in the toxic effect of 7β-OHCH.
Id. However, according to the Specification, “the mechanism of action of
7β-OHCH, whether or not esterified at C3-OH, . . . ‘in vitro’ was far from
being elucidated.” Id.
The Specification discloses:
Surprisingly, it has now been found that the sterol
derivatives according to the invention, having a 7beta-
hydroxycholesterol basic structure bearing substituents in
position 3 and protective groups in position 7, would
simultaneously permit inhibition of glycolysis, essential for the
energy supply of the high-grade cancerous astrocyte and, at the
same time, restore mitochondrial respiration, which is also
“lethal” for this cell.
Id. The Specification further discloses that “the sterol derivatives according
to the invention also have activity with respect to stem cells, thus permitting
total destruction of the glioblastoma cells.” Id. Based on these properties,
the Specification concludes that one can envisage the use of the disclosed
sterol derivatives to treat: malignant haemopathies of the myeloid type,
neuroblastomas, melanomas, and lymphomas. Id. at 5.
Claims 23–26, 28, 29, 31–37, 39–46, 48–50, and 52–62 are on appeal.
Claim 23 is representative and reads as follows:
23. A compound of formula (I) having a 7beta
hydroxycholesterol basic structure
Appeal 2019-004144
Application 14/399,336

3
in which
A represents:
an -(R1)n- group in which R1 is an amino acid
residue, n = 1 or 2, each R1 being identical or different,
and the N-terminal end of said amino acid is optionally
substituted with an arylalkoxycarbonyl group; or
a -C(O) -R6 group in which R6 is a saturated
heterocycle comprising 5 to 14 members and including 1
or 2 heteroatoms, unsubstituted or substituted with at
least one linear or branched C1-C6 alkyl
B represents:
a -C(O)-R7 group in which R7 is a C1-C12 alkyl,
linear or branched; or R7 represents OR8, in which R8 is a
linear or branched, C1 -C12 alkyl.
Appeal Br. 39–40.
Appeal 2019-004144
Application 14/399,336

4
The Examiner rejected claims 23–26, 28, 29, 31–37, 39–46, 48–50,
and 52–62 under 35 U.S.C. § 103(a) as obvious over the combination of
Axelson,3 Xian,4 Won Hyun,5 Reckewell,6 and Fieser.7
REJECTION OF PENDING CLAIMS AS OBVIOUS
In finding the pending claims obvious, the Examiner found that each
of Axelson, Won Hyun, and Reckewell disclosed that the below 7β-
hydroxycholesterol compound was cytotoxic to various types of tumor cells.
Ans. 3. The Examiner acknowledged that these references did not teach 3,7-
diesters of this compound, as recited in the pending claims, but found that
Xian disclosed esters of 7β-hydroxycholesterol. Id. at 4. The Examiner then
concluded that the claims were obvious because “an ester is ordinarily
unpatentable over the alcohol from which it is derived” and because “the
esters, as exemplified by Xian et al., . . . are well known prodrugs.” Id.
(citing Ex parte Korten, 71 USPQ 173 (Bd. App. 1946)).

3 Axelson et al., WO 97/45440, published Dec. 4, 1997 (“Axelson”).
4 Xian et al., Studies on the Synthesis and Antitumor Activities of Oxysterol
Derivatives, Chinese Journal of Medicinal Chemistry (2005) (“Xian”).
5 Won Hyun et al., Effects of Combinations of 7β-hydroxycholesterol and
Anticancer Drugs on Ionizing Radiation on the Proliferation of Cultured
Tumor Cells, 22(2A) Anticancer Research 943–948 (2002).
6 Reckewell et al., In Vitro Study of the Cytotoxicity and Selectivity of 7β-
hydroxycholesterol, 37(2) Arzneimittel-Forschung 139–141 (1987)
(“Reckewell”).
7 Fieser et al., “α” – Spinasterol, 71 Journal of the American Chemical
Society 2226–30 (1949) (“Fieser”).
Appeal 2019-004144
Application 14/399,336

5
Appellant argues that the Examiner did not identify a “suggestion to
modify either 7β-hydroxycholesterol of AXELSON, WON, [and]
RECKEWELL . . . or any of the esters of XIAN to approach [the] compound
of claim 23.” Appeal Br. 12. More specifically, Appellant argues that “none
of [the cited] references discloses or suggests the structure of the moiety A
of claim 23.” Reply Br. 2.
As stated in In re Oetiker, 977 F.2d 1443, 1445 (Fed. Cir. 1992):
“[T]he examiner bears the initial burden . . . of presenting a prima facie case
of unpatentability.” Appellant has persuaded us that the Examiner has not
carried the burden of establishing that the claimed invention would have
been obvious over the cited art.
We recognize that the claimed compounds are esters — or, more
specifically, diesters — of the 7β-hydroxycholesterol compound disclosed in
Axelson, Won, and Reckewell. We further recognize “an ester is ordinarily
unpatentable over the alcohol from which it is derived, since esterification is
such a well understood and widely practiced procedure in the chemical art,
generally, that the conception of an ester derived from a known alcohol is
not inventive, broadly.” Ex Parte Korten, 71 USPQ 173, *1 (Pat & Tr.
Office Bd. App. 1946) (affirming the examiner’s determination that a
“broadly stated ester of a given alcohol is not patentable over the alcohol
itself”). However, this is not a case where Appellant has broadly claimed
esters of 7β-hydroxycholesterol. Rather, Appellant has claimed compounds
having specific ester moieties. The question before us is thus not, broadly
speaking, whether esters of the prior art 7β-hydroxycholesterol compound
would have been obvious, but whether a compound having the specific ester
moieties recited in claim 23 would have been obvious.
Appeal 2019-004144
Application 14/399,336

6
In Takeda, the Federal Circuit provided the following guidance on
analyzing obviousness based on the structural similarity of a prior art
compound to the claimed compound:
Our case law concerning prima facie obviousness of structurally
similar compounds is well-established. We have held that
“structural similarity between claimed and prior art subject
matter, proved by combining references or otherwise, where the
prior art gives reason or motivation to make the claimed
compositions, creates a prima facie case of obviousness.”
Dillon, 919 F.2d [688,] 692 [(Fed. Cir. 1990)]. In addition to
structural similarity between the compounds, a prima facie case
of obviousness also requires a showing of “adequate support in
the prior art” for the change in structure. In re Grabiak, 769
F.2d 729, 731–32 (Fed. Cir. 1985).

We elaborated on this requirement in the case of In re Deuel, 51
F.3d 1552, 1558 (Fed. Cir. 1995), where we stated that
“[n]ormally a prima facie case of obviousness is based upon
structural similarity, i.e., an established structural relationship
between a prior art compound and the claimed compound.”
That is so because close or established “[s]tructural
relationships may provide the requisite motivation or
suggestion to modify known compounds to obtain new
compounds.” Id. A known compound may suggest its homolog,
analog, or isomer because such compounds “often have similar
properties and therefore chemists of ordinary skill would
ordinarily contemplate making them to try to obtain compounds
with improved properties.” Id. We clarified, however, that in
order to find a prima facie case of unpatentability in such
instances, a showing that the “prior art would have suggested
making the specific molecular modifications necessary to
achieve the claimed invention” was also required. Id. (citing
In re Jones, 958 F.2d 347 (Fed. Cir. 1992); Dillon, 919 F.2d
688; Grabiak, 769 F.2d 729; In re Lalu, 747 F.2d 703 (Fed. Cir.
1984)).
Takeda Chem. Indus., Ltd. v. Alphapharm Pty. Ltd., 492 F.3d 1350, 1356
(Fed. Cir. 2007) (emphasis added).
Appeal 2019-004144
Application 14/399,336

7
Under the framework set forth in Takeda, in order to support that it
would have been obvious to modify the 7β-hydroxycholesterol compound
disclosed in the art to include the ester moieties recited in claim 23 at the 3
and 7 positions, there must have been a reason why the “prior art would have
suggested making the specific molecular modifications necessary to achieve
the claimed invention.” Id. (quotation marks and citations omitted). Here,
the only explanation offered by the Examiner as to why the ordinary artisan
would have modified the prior art 7β-hydroxycholesterol compound to
include moiety A at the 3 position and moiety B at the 7 position is to point
to the structural similarity between an ester and an alcohol. Accordingly, we
find that the Examiner has not carried the burden to establish that the
claimed compound would have been obvious over the cited art. As this
deficiency is common to the Examiner’s rejection of all of the pending
claims, we reverse the Examiner’s rejection of claims 23–26, 28, 29, 31–37,
39–46, 48–50, and 52–62 under 35 U.S.C. § 103(a) as obvious over the
combination of Axelson, Xian, Won Hyun, Reckewell, and Fieser.

Appeal 2019-004144
Application 14/399,336

8
CONCLUSION
In summary:
Claims
Rejected
35 U.S.C. § References(s)/
Basis
Affirmed Reversed
23–26, 28,
29, 31–37,
39–46, 48–
50, 52–62
103 Axelson,
Xian, Won
Hyun,
Reckewell,
Fieser
23–26, 28,
29, 31–37,
39–46, 48–
50, 52–62
Overall
Outcome
23–26, 28,
29, 31–37,
39–46, 48–
50, 52–62

REVERSED