Fr¿d¿ric Sedel et al.

Patent Trials and Appeals Board

May 14, 2020

13639752 - (D) (P.T.A.B. May. 14, 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.
13/639,752 11/14/2012 Frédéric Sedel 4279-102 9412
6449 7590 05/14/2020
ROTHWELL, FIGG, ERNST & MANBECK, P.C.
607 14TH STREET, N.W.
SUITE 800
WASHINGTON, DC 20005
EXAMINER
PARAD, DENNIS J
ART UNIT PAPER NUMBER
1612
NOTIFICATION DATE DELIVERY MODE
05/14/2020 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):
PTO-PAT-Email@rfem.com
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
__________

BEFORE THE PATENT TRIAL AND APPEAL BOARD
__________

Ex parte FRÉDÉRIC SEDEL and AGNÈS BELLANGER
__________

Appeal 2019-005635
Application1 13/639,752
Technology Center 1600
__________

Before DONALD E. ADAMS, ERIC B. GRIMES, and
RACHEL H. TOWNSEND, Administrative Patent Judges.

TOWNSEND, Administrative Patent Judge.

DECISION ON APPEAL
This is an appeal under 35 U.S.C. § 134 involving claims to a biotin
composition for oral administration, which have been rejected as obvious.
We have jurisdiction under 35 U.S.C. § 6(b).
We affirm.
STATEMENT OF THE CASE
Biotin is a “water-soluble vitamin which is naturally found in many
foods.” (Spec. 1.) “In mammals, biotin acts as a cofactor for four

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 Assistance
Publique-Hopitaux De Paris and Medday Pharmaceuticals. (Appeal Br. 2.)
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metabolism” enzymes and “it has also been shown that biotin can regulate
the expression of many genes.” (Id. at 1–2.)
Commercially available oral dosage forms of biotin exist. (Id. at 4.)
However, many contain other active ingredients and “less than 1 mg of
biotin.” (Id.) One dosage form “contains only biotin, as active ingredient”
but includes only “5 mg of biotin per unit dose.” (Id.) Appellant’s invention
is an oral dosage form of biotin that provides “a large amount of biotin for
each unit dose.” (Id.)
Claims 23, 25–27, 29, and 30 are on appeal. Claim 23 is
representative and reads as follows:
23. A composition for oral administration in unit dosage form,
wherein said composition is formulated for human
administration and consists of at least 100 mg biotin per unit
dose as sole active ingredient, and one or more excipients,
wherein said unit dosage form is a gel capsule, a tablet, a film-
coated tablet, a lozenge or a pill.
(Appeal Br. 26.)
The prior art relied upon by the Examiner is:
Name Reference Date
McCarty US 5,929,066 July 27, 1999
A. Reddi et al., Biotin Supplementation Improves Glucose and Insulin
Tolerances in Genetically Diabetic KK Mice, 42 Life Sciences 1323–30
(1988)
C. Revilla-Monsalve et al., Biotin supplementation reduces plasma
triacylglycerol and VLDL in type 2 diabetic patients and in nondiabetic
subjects with hypertriglyceridemia, 60 Biomedicine & Pharmacotherapy
182–185 (2006)
Diverse Populations Collaborative Group, Weight-Height Relationships
and Body Mass Index: Some Observations From the Diverse Populations
Collaboration, 128 Am. J. Phys. Anthropol. 220–29 (2005) (“DPCG”)
FMC, Avicel® PH Microcrystalline Cellulose, Material Safety Data
Sheet, 2014.
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The following ground of rejection by the Examiner is before us on
review:
Claims 23, 25–27, 29, and 30 under 35 U.S.C. § 103(a) as
unpatentable over Revilla-Monsalve, Reddi, McCarty, DPCG, and FMC.
DISCUSSION
The Examiner finds that Revilla-Monsalve teaches a pharmaceutical
composition that contains 5 mg of biotin as the sole active ingredient, as
well as including the excipient Avicel® in an oral administration dosage
form that is used to reduce hyperglycemia and hypertriglyceridemia in a
“diabetic state.” (Non-Final Action2 3–4, 6.) The Examiner finds that FMC
teaches that Avicel® is microcrystalline cellulose (MCC). The Examiner
further finds that Revilla-Monsalve “cited a study of ‘rats consuming a diet
containing 100 mg/kg of biotin during 21 days’ (page 184, col 2, third full
paragraph).” (Ans. 9.)
The Examiner recognizes that the amount of biotin exemplified in
Revilla-Monsalve is less than the minimum amount required by the claims.
(Non-Final Action 4.) However, the Examiner concludes that it would have
been obvious to optimize the amount of biotin in the Revilla-Monsalve
dosage form to at least 100 mg of biotin in light of the combined teachings
of Reddi, McCarty, and DPCG. (Id. at 4–6; Ans. 11.) In particular, the
Examiner finds that Reddi, an article cited in Revilla-Monsalve, “discovered
that high dose biotin treatment[, 2mg of biotin/kg,] is also useful for non-
insulin dependent diabetes by lowering post-prandial glucose levels and

2 The Non-Final Action is dated October 1, 2018.
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improving tolerance to glucose and insulin resistance” besides being useful
for treating insulin-dependent diabetes. (Id.) The Examiner relies on DPCG
for its teaching of average weight in human populations and concluding that
the human equivalent dosage in Reddi is about 153 mg for males and about
134 mg for females.3 (Non-Final Action 5, 6.)
The Examiner further finds that “McCarty teaches a unit dosage” of
biotin for oral administration of up to 200 mg per day in human patients to
treat diabetes. (Id. at 4.) In addition, McCarty teaches “no side effects or
toxicities were noted in clinical studies with oral biotin intakes of up to 200
mg daily.” (Id. at 4–5.) In light of the foregoing, the Examiner concludes
that the prior art teaches that “the dosage amount of biotin is a result-
effective variable” for treating diabetes (Non-Final Action 7) and that, in
combination, the prior art “provides a motivation and reasonable expectation
of success for formulating high dosages of biotin for treating diabetes” of at
least 100 mg (Ans. 10; Non-Final Action 6–7) and that doing so is a matter
of “determining optimum or workable ranges by routine experimentation”
(Non-Final Action 5–6; Ans. 12).
Regarding McCarty, which the Examiner acknowledges also teaches
administering chromium in a range of from about 50–1000 micrograms per
day (Ans. 13), the Examiner explains “whether or not additional actives are
taught by McCarty, this does not teach away from the fact that the reference
suggests that administering higher doses of biotin [as compared to the
dosage of Revilla-Monsalve] is well known and has pharmacological utility,

3 The Examiner arrived at this amount by multiplying the dosage (mg/kg) in
Reddi by the average weight for human males or females. (Id.)
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which is dose-dependent.” (Ans. 14.) The Examiner explains that “[t]here
is no evidence in the cited references or in any of Appellant’s data that teach
away from formulating a unit dosage form having a high dose of biotin,
including 100 mg or more.” (Ans. 14.) The Examiner further finds that the
Specification “makes no mention of the criticality of 100 mg or more
biotin.” (Ans. 7.)
We agree with the Examiner’s conclusion of obviousness, but rely
only on McCarty. In affirming a multiple reference rejection under 35
U.S.C. § 103, the Board may rely on fewer than all of the references relied
on by the Examiner in an obviousness rationale without designating it as a
new ground of rejection. In re Bush, 296 F.2d 491, 496 (CCPA 1961).
McCarty teaches two compounds “administered orally or parenterally
in daily dosages which provide between 50 and 1,000 μg of chromium and
between 25 μg and 200 mg biotin” for treating Type II diabetes. (McCarty
Abstract.) In addition, as the Examiner noted, McCarty teaches a preferred
dosage range for biotin in the combination therapy is between 1 mg to 100
mg. (Id. at 3: 9–12.) McCarty teaches that “[f]or oral administration, the
chromic picolinates and biotin may be provided as a tablet . . . [or] hard or
soft capsule.” (Id. at 3:13–16.)
Regarding the oral dosage form, McCarty further teaches that the
composition is a pharmaceutically acceptable composition and may include
excipients, including “lubricating agents such as magnesium stearate, stearic
acid or talc.” (Id. at 3:16–34.)
Furthermore, as the Examiner noted, McCarty teaches that no side
effects or toxicities were noted in previous clinical studies with oral biotin
intakes of up to 200 mg daily. (Id. at 1:63–66.)
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Although McCarty does teach that the amounts of chromium and
biotin are selected so that the chromium and biotin together “provide a
greater than additive effect” in treating diabetes (id. Abstract; Appeal Br. 23
(“McCarty stresses the importance of the synergistic effects of chromic
tripicolinate and biotin.”)), McCarty does not require that these two
compounds must be administered as a combination of active ingredients in a
single dosage form for combination therapy to be achieved. (Compare
McCarty 2:34–47 (noting the compounds individually), with id. at 2:48–50
(noting the use of the two compounds combined in a pharmaceutical
composition).) Indeed, McCarty suggests that commercially available forms
of these drugs sold separately could be used in the method so long as they
were used in the dosage range. (Id. at 3:1–13.) The claims of McCarty
indicating that biotin is administered orally (claim 7) and chromic
tripicolinate is administered parenterally (claim 8) further support the
conclusion that McCarty does not require biotin and chromic tripicolinate to
be combined into a single dosage form to administer the combined therapy.
Thus, we do not find persuasive Appellant’s argument that McCarty
“suggests only a combination of biotin and chromic tripicolinate” as a
single dosage form (Reply Br. 10; Appeal Br. 23–24).
We note that taking the minimum amount of pills is generally more
desirable for a patient than taking numerous pills to obtain the same dosage
amount. With that, and McCarty’s suggestion that 100 mg is part of a
preferred range for administration to a diabetic patient but that up to 200 mg
can be used, and its teaching that dosage forms can be tablets or capsules,
making a dosage form of biotin in a capsule or tablet to include 100 mg
biotin and at least one excipient would have been obvious to one of ordinary
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skill in the art with a reasonable expectation of success.4 “[W]here the
general conditions of a claim are disclosed in the prior art, it is not inventive
to discover the . . . workable ranges by routine experimentation.” In re
Aller, 220 F.2d 454, 456 (CCPA 1955).
“It is well-established that the Board is free to affirm an examiner’s
rejection so long as ‘appellants have had a fair opportunity to react to the
thrust of the rejection.”’ In re Jung, 637 F.3d 1356, 1365 (Fed. Cir.
2011) (citing In re Kronig, 539 F.2d 1300, 1302–03 (CCPA 1976)). We
find this to be the case given the arguments Appellant made and discussed
below.
Appellant argues that McCarty only explicitly discloses a 3 mg unit
dosage form of biotin (Appeal Br. 18), much like the many prior art articles
cited by Appellant describing unit dosages of biotin administered (Appeal
Br. 19–21), and is another reason, combined with the fact that it “discloses
an extraordinarily broad range of daily dosages (to be combined with
chromic tripicolinate),” that McCarty does not provide a motivation to

4 Regarding the requirement of claims 25 and 29 that the excipient be talc or
MCC, we note that talc is a lubricating agent taught in McCarty. The
selection of this excipient would have been obvious to one having ordinary
skill in the art. Sinclair & Carroll Co. v. Interchemical Corp., 325 U.S. 327,
335 (1945) (“Reading a list and selecting a known compound to meet known
requirements is no more ingenious than selecting the last piece to put into
the last opening in a jig-saw puzzle. It is not invention.”); see also Merck &
Co. Inc. v. Biocraft Laboratories, Inc., 874 F.2d 804, 807 (Fed. Cir. 1989).
Furthermore, Revilla-Monsalve teaches that it was known in the art that
biotin is compatible with an excipient such as MCC and in an oral dosage
form. It would have been obvious to include MCC in an oral dosage form of
100 mg of biotin that includes an excipient suggested by McCarty.

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prepare a high-unit dose composition “wherein biotin is the sole active
ingredient” (id. at 19). We disagree with Appellant’s conclusion. The prior
art referenced in McCarty using low doses of biotin, at or below the range of
Revilla-Monsalve, along with the other prior art studies Appellant cites, does
not detract from McCarty’s teaching that a daily dosage of up to 200 mg of
biotin, and preferably up to 100 mg, is within the scope of McCarty’s
teachings. That McCarty itself does not make such a composition (Reply
Br. 4) does not evidence non-obviousness of such a unit dosage form. “It is
well settled that a prior art reference is relevant for all that it teaches to those
of ordinary skill in the art.” In re Fritch, 972 F.2d 1260, 1264 (Fed. Cir.
1992).
We also do not find persuasive Appellant’s argument that McCarty
teaches away from an oral dosage form of biotin as the only active
ingredient and at a high dosage level (Appeal Br. 24; Reply Br. 11). A
reference teaches away from a claimed invention if it “criticize[s],
discredit[s], or otherwise discourage[s]” modifying the reference to arrive at
the claimed invention. In re Fulton, 391 F.3d 1195, 1201 (Fed. Cir. 2004).
The fact that McCarty promotes the use of biotin together with chromic
tripicolinate is not evidence that McCarty criticizes, discredits, or
discourages a single dosage form of biotin. And, indeed, as discussed above
McCarty suggests combination therapy in which each compound is
administered as a separate dosage form. Moreover, the fact that McCarty
does not provide an exemplification of a dosage at the high end of the
disclosed range, does not evidence criticism, discrediting or discouragement
from making a single dosage form in this disclosed acceptable range.
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Appellant argues that “the present application . . . disclose[s]
unexpected advantages of high-unit dose biotin compositions” (Appeal Br.
22) and “McCarty provides no examples whatsoever describing the actual
production of a composition, much less its effectiveness upon administration
to a patient” (id. at 23) which supports a conclusion that “a person of
ordinary skill in the art would not have been motivated to, nor would have
had a reasonable expectation of successfully formulating a unit dose of at
least 100 mg biotin as sole active ingredient” (id. at 24). We do not find
Appellant’s argument persuasive of non-obviousness. We have addressed
motivation above regarding a reason to make a single dose formulation of
biotin that has at least 100 mg biotin therein. That McCarty does not
provide an example of the effectiveness of such a composition is not
persuasive of non-obviousness of the composition, which has no efficacy
limitations. See Catalina Mktg. Int’l, Inc. v. Coolsavings.com, Inc., 289 F.3d
801, 809 (Fed. Cir. 2002) (“[T]he patentability of apparatus or composition
claims depends on the claimed structure, not on the use or purpose of that
structure.”).
Furthermore, regarding a reasonable expectation of success, the prior
art teaches that oral dosage forms of biotin are known and the Examiner’s
position is that one of ordinary skill in the art using routine experimentation
would have found it obvious to formulate and achieve an oral dosage form
that includes 100 mg biotin. (See, e.g., Ans. 8, 10.) Appellant does not
provide any argument or evidence that formulating such a dosage form
would have required extraordinary skill or would have been unexpectedly
difficult. Rather, Appellant provides the Declaration of Dr. Frédéric Sedel
that “demonstrates the significant unexpected advantages of administering
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high-dose biotin to patients suffering from multiple sclerosis.” (Appeal Br.
22.) Such evidence regarding unexpected effectiveness in use with multiple
sclerosis patients does not establish the formulation containing 100 mg
biotin itself was unexpectedly achieved.
Thus, we affirm the Examiner’s rejection of claims 23, 25–27, 29, and
30 under 35 U.S.C. § 103(a) as unpatentable over Revilla-Monsalve, Reddi,
McCarty, DPCG, and FMC.
DECISION SUMMARY

Claims
Rejected
35 U.S.C.
§
Reference(s)/Basis Affirmed Reversed
23, 25–27,
29, 30
103 Revilla-Monsalve,
Reddi, McCarty,
DPCG, FMC
23, 25–27,
29, 30

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). See 37 C.F.R.
§ 1.136(a)(1)(iv).
AFFIRMED