Donald Poirier et al.

Patent Trials and Appeals Board

Dec 3, 2020

2020002058 (P.T.A.B. Dec. 3, 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.
14/007,577 12/06/2013 Donald Poirier LAVE.P0005US 8052
108197 7590 12/03/2020
Parker Highlander PLLC
1120 South Capital of Texas Highway
Bldg. 1, Suite 200
Austin, TX 78746
EXAMINER
BADIO, BARBARA P
ART UNIT PAPER NUMBER
1628
NOTIFICATION DATE DELIVERY MODE
12/03/2020 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):
docket@phiplaw.com
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
____________

BEFORE THE PATENT TRIAL AND APPEAL BOARD
____________

Ex parte DONALD POIRIER, RENE MALTAIS, and
JENNY ROY
____________

Appeal 2020-002058
Application 14/007,577
Technology Center 1600
____________

Before JOHN E. SCHNEIDER, RYAN H. FLAX, and
RACHEL H. TOWNSEND, Administrative Patent Judges.

FLAX, Administrative Patent Judge.

DECISION ON APPEAL
This is a decision on appeal under 35 U.S.C. § 134(a) involving
claims to an inhibitor of 17β-HSD1. Appellant appeals the rejection of
claim 2 under 35 U.S.C. § 103(a).1,2 We have jurisdiction under 35 U.S.C.
§ 6(b).
We reverse.

1 “Appellant” herein refers to the “applicant” as defined by 37 C.F.R. § 1.42.
Appellant identifies “Université Laval” as the real party-in-interest. Appeal
Br. 3.
2 Oral argument was heard on November 16, 2020; a transcript of the
hearing is, or will be made, a part of the record.
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STATEMENT OF THE CASE
Claim 2 is the sole claim on appeal; it is reproduced below:
2. An inhibitor of 17β-HSD1, wherein the inhibitor is
of the structure:

wherein R is halo, -NH2, alkyl, -OCH2CH2Br, aralkyl,
carboxy, -CH2-heterocyclyl, heterocyclyloyl, -C(O)N(R')(R") or
-B(OH)2, wherein R' and R" are independently or simultaneously
H or alkyl, or R' and R" are joined together, along with the
nitrogen atom to which they are attached, to form a heterocyclic
ring,
or a pharmaceutically acceptable salt or tautomer thereof.
Appeal Br. 15 (Claims Appendix). The Final Action indicates that claims 2–
47 are pending, with claims 6–44 being withdrawn and claims 3 and 4 being
objected to for depending from a rejected claim. Final Action 1–2. Claims
5, 45, and 47 stand allowed. Id.
The Specification states:
17β-Hydroxysteroid dehydrogenase type (17β-HSD1)
transforms estrone (E1) into estradiol (E2), the most potent
natural ligand for the estrogen receptor (ER). This enzyme also
catalyzes the reduction of dehydroepiandrosterone (DHEA) into
5-androstene-3β, 17β-diol (Δ5-diol), a weaker estrogen but
especially important after menopausis. Inhibitors of 17β-HSD1
are thus interesting therapeutic agents for the control of estrogen-
dependent diseases such as breast cancers and endometriosis.
Spec. ¶ 2.
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The following rejection is on appeal:
Claim 2 stands rejected under 35 U.S.C. § 103(a) over Laplante,3
Bolger,4 Dorn,5 Price,6 Cook,7 Peters,8 and Yarger.9
DISCUSSION
I. LEGAL STANDARDS
“[T]he examiner bears the initial burden, on review of the prior art or
on any other ground, of presenting a prima facie case of unpatentability.
[Once] that burden is met, the burden of coming forward with evidence or
argument shifts to the applicant.” In re Oetiker, 977 F.2d 1443, 1445 (Fed.
Cir. 1992). Arguments made by Appellant in the Appeal Brief and properly
presented in the Reply Brief have been considered. See 37 C.F.R.
§ 41.37(c)(1)(iv) (2017); see also Ex parte Borden, 93 USPQ2d 1473, 1474
(BPAI 2010) (informative) (“Any bases for asserting error, whether factual
or legal, that are not raised in the principal brief are waived.”).
When analyzing obviousness, “[t]he 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,

3 Yannick Laplante et al., Estradiol and estrone C-16 derivatives as
inhibitors of type 1 17β-hydroxysteroid dehydrogenase: Blocking of ER+
breast cancer cell proliferation induced by estrone, 16 J. BIOORG. MED.
CHEM. 1849–60 (2008) (“Laplante”).
4 U.S. Patent 5,232,917, issued Aug. 3, 1993 (“Bolger”).
5 U.S. Patent 5,512,570, issued Apr. 30, 1996 (“Dorn”).
6 U.S. Patent 6,933,312 B2, issued Aug. 23, 2005 (“Price”).
7 U.S. Patent 5,952,319, issued Sept. 14, 1999 (“Cook”).
8 U.S. Application Publication 2009/0029957 A1, published Jan. 29, 2009
(“Peters”).
9 U.S. Application Publication 2010/0130463 A1, published May 27, 2010
(“Yarger”).
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416 (2007). “[W]hen the question is whether a patent claiming the
combination of elements of prior art is obvious,” the answer depends on
“whether the improvement is more than the predictable use of prior art
elements according to their established functions.” Id. at 417. “If a person
of ordinary skill can implement a predictable variation [of a known work],
§ 103 likely bars its patentability.” Id.
“[R]ejections on obviousness grounds cannot be sustained by mere
conclusory statements; instead, there must be some articulated reasoning
with some rational underpinning to support the legal conclusion of
obviousness.” Id. at 418 (quoting In re Kahn, 441 F.3d 977, 988 (Fed. Cir.
2006)). An invention
composed of several elements is not proved obvious merely by
demonstrating that each of its elements was, independently,
known in the prior art. Although common sense directs one to
look with care at a patent application that claims as innovation
the combination of two known devices according to their
established functions, it can be important to identify a reason that
would have prompted a person of ordinary skill in the relevant
field to combine the elements in the way the claimed new
invention does.
Id.
With these standards in mind, we address the Examiner’s rejections
and Appellant’s arguments thereover.
II. ANALYSIS
The Examiner determines that Laplante teaches an ether prodrug in its
intermediate compound “6m,” and “[b]ecause ethers are known prodrug
moieties, prior art compound 6m and the instantly claimed ether derivative
would be readily recognized as prodrug derivatives of prior art compound
4m.” Final Action 3–4; Answer 3–4 (citing Laplante, generally, and
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specifically at 1851 (Table 1)). The Examiner takes the position that Bolger,
Dorn, and Price teach that ethers are well-known prodrugs, which offer
advantages in drug efficacy, reduction of side effects, and stability. Answer
4–5. The Examiner identifies the “ether derivatives” of the claimed
invention include the claimed R group OCH2CH2Br––a compound that, as
claimed, is not expressly disclosed in the cited prior art. Id. at 3–6. The
Examiner cites Cook, Peters, and Yarger as teaching that, in the steroid art, it
was known to make substitutions with alkyls, alkoxy groups, halogen
groups, and hydroxyls. Id. at 5–6. The Examiner summarizes his position
as follows:
In essence, because the production of prodrugs were well
known in the art at the time of the present invention, the
production of other prodrugs derivatives of compound 4m,
including other ether derivatives thereof, is rendered prima facie
obvious absen[t] a showing of unexpected and unobvious results.
Id. at 8.
Appellant argues there would not have been a motivation to modify
Laplante’s disclosed compound because Laplante does not characterize the
6m compound as a prodrug. Appeal Br. 5–8 (citing the Declaration of Rene
C.-Gaudreault under 37 C.F.R. § 1.132, dated Sept. 25, 2018 (“Gaudreault
Declaration”)). Dr. Gaudreault states that, “at the time the present
application was filed, [the skilled artisan] would [not] have considered
[Laplante’s] 6m to be a prodrug of 4m.” Gaudreault Declaration ¶ 3.
Appellant also argues that ether moieties are distinguishable from “aliphatic
ethers” because the latter, such the claimed OCH2CH2Br R group, are not
well-known prodrug moieties and “none of the cited art teaches that aliphatic
ethers are well-known prodrug moieties.” Id. at 7–9. Dr. Gaudreault states
that “aliphatic ethers should not be confused with particular cases of
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activated ether-like acetals (R-O-CH2-O-R), which are much [more] prone to
hydrolysis as compared to aliphatic ethers and could potentially be used as
prodrug groups.” Gaudreault Declaration ¶ 5. Appellant argues that “the
Examiner has not provided any reasons why person of skill in the art would
choose to make the specific ether derivatives, -OCH2CH2Br or the
heterocyclyloyl, covered by claim 2.” Appeal Br. 9.
We are persuaded by Appellant’s argument. We particularly agree
with Appellant’s position: “[l]acking from the examiner’s rejection is any
reason or explanation for why a person of skill in the art would have chosen
to modify either 4m or 6m of Laplante in the specific manner necessary to
make either the -OCH2CH2Br derivative or any of the other derivatives
covered by claim 2.” Appeal Br. 10.
It is unclear from the Examiner’s statements exactly why a prodrug
would meet the claimed compound, which must be an inhibitor of
17β-HSD1, where the Examiner’s evidence indicates that prodrugs are not
active compounds, but are compounds that transform into active drugs
(compounds possessing intrinsic activity are not true prodrugs). See, e.g.,
Bolger, 4:56–5:11; see also Reply Br. 2 (renewing this argument). Further,
Laplante indicates that its compound 6m, which the Examiner identifies as a
prodrug that would have rendered the claimed compound obvious, exhibits a
38% inhibition of 17β-HSD1, with no indicated benefits in, e.g., delivery
characteristics or therapeutic value that the Examiner indicates make
prodrugs useful, or any indication that it will be transformed in the body into
an active drug via “some metabolic process.” See Laplante, 1852; see also
Bolger, 4:56–5:11; and Dorn, 12:29–35. Thus, exactly why compound 6m
would qualify as a prodrug is unclear, as is why a skilled artisan would have
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believed a prodrug for Laplante’s compound 4m would have been required
at all, as there is no indication in the reference, or otherwise, that its
compound 4m (the ultimate, desired active compound according to the
Examiner) has stability, delivery, therapeutic value, or side effect problems
that the prior art and Examiner indicate would make a prodrug desirable.
The Examiner’s position appears somewhat internally inconsistent.
As Appellant points out, Laplante’s compounds 4m and 6m were
17β-HSD1 inhibiting compounds, with Laplante focusing on 4m as the best
inhibitor (at 77% inhibition compared to the weaker 38% of the 6m
compound). Laplante 1852. However, even this best-inhibiting compound
was “expected to display some estrogenic activity,” which was “unwanted
activity” because “[a] 17β-HSD1 inhibitor must be devoid of estrogenic
activity to be considered useful in the treatment of breast cancer.” Id.
Ultimately, Laplante explained that any strategy for reducing this estrogenic
activity of 4m also decreased inhibitory activity. Id. at 1855 (conclusions).
Thus, Laplante is ultimately unclear whether 4m (or 6m) actually provides
useful pharmaceutical compounds.
Laplante’s 6m compound was relatively undiscussed. See generally
id. However, the initial disclosure of compounds 4m and 6m shows only
that the 4m compound may become the 6m compound, but does not indicate
the reverse, as would be required of a prodrug to fit the Examiner’s
determinations. Id. at 1851 (Scheme 1: the arrow at step “e” points only
from 4m to 6m, indicating 4m can become 6m, but not the reverse). Thus,
although it might be possible to design a prodrug for 4m based on 6m, the
cited prior art does not suggest doing so.
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Moreover, the evidence supports that the compound of claim 2,
focused upon by the Examiner here, that is, where the R group is
-OCH2CH2Br, is an aliphatic ether not an aldehyde ether as taught as 6m by
Laplante, which Appellant’s witness indicates were known to have different
properties and characteristics such that the claimed compound would not
have been considered a candidate for a prodrug (for 4m or otherwise).
For the reasons set forth above, we find that the Examiner has not
established that the skilled artisan would have selected Laplante’s 4m
compound as particularly useful, or would have been motivated to adapt the
related compound 6m to be a prodrug for the 4m compound or even to
modify 6m to actually meet the claimed composition. Such drug strategies
and modifications may have been possible for the skilled artisan, but
evidence is lacking that there would have been a motivation to do so. Thus,
we reverse the rejection of claim 2.
CONCLUSION
In summary:

Claim
Rejected 35 U.S.C. § Reference(s)/Basis Affirmed Reversed
2 103(a)
Leplante, Bolger,
Dorn, Price, Cook,
Peters, Yarger
2

REVERSED