Medy-Tox, Inc.

Patent Trials and Appeals Board

Jul 16, 2021

PGR2019-00062 (P.T.A.B. Jul. 16, 2021)

Trials@uspto.gov Paper 66
571-272-7822 Date: July 16, 2021

UNITED STATES PATENT AND TRADEMARK OFFICE

BEFORE THE PATENT TRIAL AND APPEAL BOARD

GALDERMA S.A.; GALDERMA LABORATORIES, INC.; GALDERMA
LABORATORIES LP; GALDERMA RESEARCH & DEVELOPMENT
SNC; NESTLÉ SKIN HEALTH, INC.; NESTLÉ SKIN HEALTH S.A.; and
NESTLÉ S.A.,
Petitioner,
v.
MEDY-TOX, INC.,
Patent Owner.

PGR2019-00062
Patent 10,143,728 B2

Before ZHENYU YANG, CHRISTOPHER G. PAULRAJ, and
TIMOTHY G. MAJORS, Administrative Patent Judges.
PAULRAJ, Administrative Patent Judge.
JUDGMENT
Final Written Decision
Cancelling Original Claims 1–10
Denying Patent Owner’s Non-Contingent Revised Motion to Amend With
Regard to Proposed Substitute Claims 19–27
35 U.S.C. § 328(a)

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I. INTRODUCTION
This is our Final Written Decision pursuant to 35 U.S.C. § 328(a).
For the reasons discussed below, we hereby deny Patent Owner’s non-
contingent revised Motion to Amend with regard to proposed substitute
claims 19–27. Paper 30 (“revised MTA” or “Rev. Mot.”). We do not
address the patentability of original claims 1–10, each of which is cancelled
by virtue of the non-contingent revised MTA.
A. Procedural Background and Summary
Galderma S.A., et al., (“Petitioner”) filed a Petition requesting post-
grant review of claims 1–10 of U.S. Patent No. 10,143,728 B2 (Ex. 1001,
“the ’728 patent”). Paper 2 (“Pet.”). Medy-Tox, Inc. (“Patent Owner”) filed
a Preliminary Response to the Petition. Paper 11.
We determined that the ’728 patent was eligible for post-grant review
and that Petitioner demonstrated that it is more likely than not that at least
one of the challenged claims was unpatentable. Accordingly, we instituted
trial as to claims 1–10 of the ’728 patent. Paper 14 (“Institution Decision”
or “Dec.”).
Following institution, Patent Owner did not file a Response to the
Petition to contest the unpatentability arguments presented in the Petition
with regard to the original claims, and instead chose to file a non-contingent
Motion to Amend. Paper 21. In its Motion to Amend, Patent Owner
requested that we provide Preliminary Guidance concerning the Motion to
Amend in accordance with the Board’s pilot program concerning motion to
amend practice and procedures. Mot. 3; see also Notice Regarding a New
Pilot Program Concerning Motion to Amend Practice and Procedures in
Trial Proceedings Under the America Invents Act Before the Patent Trial
and Appeal Board, 84 Fed. Reg. 9,497 (Mar. 15, 2019) (providing a patent
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3
owner with the option to receive preliminary guidance from the Board on its
motion to amend) (“Notice”). Petitioner filed an Opposition to the Motion
to Amend. Paper 26.
In response to Patent Owner’s request, we issued our Preliminary
Guidance, indicating our initial, preliminary, non-binding views on whether
Patent Owner had shown a reasonable likelihood that it had satisfied the
statutory and regulatory requirements associated with filing a motion to
amend in a post-grant review and whether Petitioner had established a
reasonable likelihood that the substitute claims are unpatentable. Paper 28
(“Prelim. Guid.); see 35 U.S.C. § 326(d); 37 C.F.R. § 42.221; see also
Notice, 84 Fed. Reg. at 9,497 (“The preliminary guidance . . . provides
preliminary, non binding guidance from the Board to the parties about the
[motion to amend].”)
Patent Owner thereafter filed the non-contingent revised MMTA
seeking to expressly cancel original claim 6 and replace the other original
claims with proposed substitute claims 19–27. See generally Rev. Mot.
Petitioner filed an Opposition to the revised MTA. Paper 40 (“Opp.”).
Patent Owner filed a Reply in support of its revised MTA, Paper 55
(“Reply”),1 and Petitioner filed a Sur-Reply in opposition to the revised
MTA, Paper 60.
After Patent Owner filed its revised MTA, the Chief Administrative
Patent Judge extended the time to complete this proceeding by six months
for good cause. Papers 32, 33, 34, 35. Prior to the oral hearing, we notified
the parties of a potential sua sponte ground of unpatentability for substitute

1 This corrected Reply replaced Patent Owner’s originally filed Reply, Paper
52.
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independent claim 19 as proposed in the revised MTA. Paper 54; see Nike,
Inc. v. Adidas AG, 955 F.3d 45, 51 (Fed. Cir. 2020) (holding that the Board
may sua sponte identify a patentability issue for a proposed substitute
claim); Hunting Titan, Inc. v. DynaEnergetics Europe GmbH, IPR2018-
00600, Paper 67 at 13 (PTAB July 6, 2020) (precedential) (explaining that
the Board may, in rare circumstances, raise a ground of unpatentability not
raised by the parties). We held the oral hearing on March 19, 2021, and the
transcript of that hearing has been entered into the record. Paper 65 (“Tr.”).
B. Real Parties-in-Interest
Petitioner initially identified Galderma S.A., Galderma Laboratories,
Inc., Galderma Laboratories LP, Galderma Research & Development SNC,
Nestlé Skin Health, Inc., Nestlé Skin Health S.A., and Nestlé S.A. as the real
parties-in-interest for Petitioner. Pet. 4–5. Petitioner later updated its
mandatory notices to indicate that Nestlé Skin Health S.A. was acquired by
EQT Partners on October 2, 2019, and that Nestlé S.A. sold Galderma S.A.,
Galderma Laboratories, Inc., Galderma Laboratories L.P., Galderma
Research & Development SNC, Nestlé Skin Health, Inc. (now SHDS, Inc.),
and Nestlé Skin Health S.A. to an investment consortium of the following:
(i) EQT Partners AB; (ii) PSP Investments; and (iii) Luxinva, a wholly
owned subsidiary of Abu Dhabi Investment Authority. Paper 4. Petitioner
contends that the consortium of investment partners are not real parties-in-
interest because they did not have any role in directing, preparing, or filing
the Petition, or any role in directing or controlling this proceeding. Id.
Patent Owner identifies Medy-Tox, Inc., Allergan Pharmaceuticals
Ireland, Allergan Pharmaceuticals Holding (Ireland), and Allergan, Inc., as
the real parties-in-interest for Patent Owner. Paper 5.
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Patent 10,143,728 B2
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The parties do not dispute the identification of the real parties-in-
interest.
C. Related Matters
Petitioner and Patent Owner report that the ’728 patent is not the
subject of any other judicial or administrative matter. Pet. 5; Paper 5, 2.
D. The ’728 Patent
The ’728 patent, titled “Long Lasting Effect of New Botulinum Toxin
Formulation,” discloses the use of an animal-protein-free botulinum toxin
composition that exhibits a longer lasting effect compared to an animal-
protein-containing botulinum toxin composition. Ex. 1001, codes (54), (57).
The patent issued from an application (No. 15/336,119) filed October 27,
2016, but claims earliest priority to a provisional application (No.
61/915,476) filed December 12, 2013. Id. at codes (60), (63).
The specification explains that commercially available botulinum
toxin A (BoNT/A) compositions, including BOTOX® (ona-BoNT/A), all
contain animal proteins such as albumin and have a duration effect of
approximately 3 months for treating conditions such as crow’s feet lines or
glabellar lines. Id. at 1:40–44. In contrast, the ’728 patent claims methods
of “locally administering a therapeutically effective amount of a botulinum
toxin composition that does not comprise an animal-derived product or
recombinant human albumin.” Id. at 32:4–7.
As noted in the specification, animal-protein-free botulinum toxin
compositions were previously disclosed in the inventors’ prior patent
applications, U.S. Application Publication No. 2010/0291136, now U.S.
Patent No. 8,617,568 (“Jung I”) (Exhibit 1006), and PCT/KR10–2012–
0112248 (“Jung II”) (Exhibit 1007), which are both incorporated by
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reference in their entirety into the ’728 patent. Id. at 2:63–3:20.2 The
specification notes that the use of polysorbate 20, methionine, and optionally
isoleucine, instead of an animal-derived protein such as albumin or gelatin,
as stabilizers for botulinum toxin eliminates the potential risk of infecting
the recipient with serum-derived pathogens or microorganisms. Id. at 6:4–9.
Furthermore, the specification indicates that an animal-protein-free
botulinum toxin composition exhibits a longer lasting effectiveness
compared to an animal-protein-containing botulinum toxin composition. Id.
at 5:47–56.
In support of its conclusion regarding longer lasting efficacy, the
specification describes the results of two clinical trials comparing an animal-
protein-free botulinum toxin composition with botulinum toxin stabilized
with human serum albumin. See id. at 13:60–31:55. Example 1 describes a
Phase III clinical study that compared the efficacy of 20 units (U) liquid
BoNTA/A (MT10109L), an animal-protein-free botulinum toxin
composition, to 20 U BOTOX® in managing moderate to severe glabellar
frown lines. Id. at 13:60–22:67. The specification indicates that the results
presented from the Phase III study “demonstrate that MT10109L is not
inferior to ona-BoNT/A in the improvement of glabellar lines and is
relatively similar in safety,” and “[w]ith its longer maintaining period of the
glabellar line improvement, convenience without the additional dilution step,
easy storage and re-usage, and animal derived protein-free constituents,

2 Petitioner relies upon Jung I and Jung II for its anticipation and
obviousness challenges presented in the Petition. Pet. 36–87. Petitioner
does not, however, argue in this proceeding that the proposed substitute
claims are anticipated or obvious. See generally Opp.
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MT10109L is a desirable substitute for the conventional powder formulation
of BoNT/A.” Id. at 22:58–67.
Example 2 describes a Phase II clinical study that compared the
efficacy of a lyophilized formulation of MT10109 versus BOTOX®, both
administered at a 20 U dose. Id. at 23:1–31:55. Based on the data from the
Phase II study, the specification concludes that “lyophilized MT10109 dosed
at 20 U demonstrates similarity to BOTOX® at early time points (e.g. day
30),” and “[f]urther, it is demonstrated that MT10109 dosed at 20 U displays
an increased sustained effect compared to BOTOX®, as the response of
treatment was seen to be increased in the MT10109 20 U group compared to
BOTOX® 20 U group at 120 days post treatment.” Id. at 31:48–55.
E. Originally Challenged Claims and Asserted Grounds in
Petition
Petitioner originally challenged claims 1–10 of the ’728 patent, of
which claim 1 is the only independent claim. In the Petition, Petitioner
advanced five grounds of unpatentability in relation to these original claims.
See Pet. 1. The grounds are summarized in the table below:
Claims Challenged 35 U.S.C. § Reference(s)/Basis
1–10 112 Indefiniteness
1–10 112 Written Description
1–10 112 Enablement
1–3, 8 102 Jung I
1–8, 10 103 Jung I, Jung II, Allergan (ELN
1145), BOTOX® COSMETIC
(Botulinum Toxin Type A) (2002)
(“2002 Label”)

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In view of Patent Owner’s election to file a non-contingent motion to
amend, none of the originally challenged claims remain at issue in this
proceeding. In particular, Patent Owner’s non-contingent revised MTA
expressly requests that we cancel original claim 6 and replace the remaining
claims with revised substitute claims 19–27. Rev. Mot. 1. Although not
expressly requested to be cancelled, we hereby also cancel original claims
1–5 and 7–10 because a non-contingent MTA is one in which “the Board
provides a final decision on the patentability of substitute claims in place of
determining the patentability of corresponding original claims.” See Notice,
84 Fed. Reg. at 9,505 (emphasis added). Accordingly, we do not address the
patentability of original claims 1–10 in this Final Written Decision insofar as
all those claims are deemed cancelled by virtue of the non-contingent
revised MTA and only address the patentability of proposed substitute
claims 19–27.
II. ANALYSIS FOR MOTION TO AMEND
A. Legal Standards for Motions to Amend
In a post-grant review, amended claims are not added to a patent as of
right, but rather must be proposed as part of a motion to amend. 35 U.S.C. §
326(d). The Board must assess the patentability of the proposed substitute
claims “without placing the burden of persuasion on the patent owner.” See
Aqua Prods., Inc. v. Matal, 872 F.3d 1290, 1328 (Fed. Cir. 2017) (en banc);
see also Lectrosonics, Inc. v. Zaxcom, Inc., IPR2018-01129, Paper 15 at 3–4
(PTAB Feb. 25, 2019) (precedential). Ordinarily, “the petitioner bears the
burden of proving that the proposed amended claims are unpatentable by a
preponderance of the evidence.” Bosch Auto. Serv. Sols., LLC v. Matal, 878
F.3d 1027, 1040 (Fed. Cir. 2017) (as amended on rehearing); see also
Lectrosonics, Paper 15 at 3–4.
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In determining whether a petitioner has proven unpatentability of the
proposed substitute claims, the Board focuses on “arguments and theories
raised by the petitioner in its petition or opposition to the motion to amend.”
Nike, 955 F.3d at 51. The Board itself also may justify any finding of
unpatentability by reference to evidence of record in the proceeding.
Lectrosonics, Paper 15 at 4 (citing Aqua Products, 872 F.3d at 1311
(O’Malley, J.)). “[O]nly under rare circumstances should the need arise for
the Board to advance grounds of unpatentability to address proposed
substitute claims that the petitioner did not advance, or insufficiently
developed, in its opposition to the motion.” Hunting Titan, Paper 67 at 9.
Before reaching the patentability issues that Petitioner argues,
however, we first consider whether Patent Owner’s revised MTA meets the
statutory and regulatory requirements of 35 U.S.C. § 316(d) and 37 C.F.R. §
42.121. Lectrosonics, Paper 15 at 4. Patent Owner bears the burden of
meeting these statutory and regulatory requirements. See “Guidance on
Motions to Amend in view of Aqua Products” (2017), available at
https://www.uspto.gov/sites/default/files/documents/guidance_on_
motions_to_amend_11_2017.pdf. Accordingly, Patent Owner must
demonstrate that: (1) the amendment proposes a reasonable number of
substitute claims; (2) the amendment does not seek to enlarge the scope of
the claims of the patent or introduce new subject matter; (3) the amendment
responds to a ground of unpatentability involved in the trial; and (4) the
original disclosure sets forth written description support for each proposed
claim. See 35 U.S.C. § 326(d); 37 C.F.R. § 42.221.
B. Proposed Substitute Claims
In its revised MTA, Patent Owner requests that we cancel original
claim 6 and replace original claims 1–5 and 7–10 with revised substitute
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claims 19–27. Rev. Mot. 1–2. Proposed substitute claim 19, which would
replace claim 1, recites (with underlining and strikethroughs representing,
respectively, text added to and deleted from claim 1, and added bracketed
letters (e.g., [a], [b], etc.) correlating to Patent Owner’s indication of specific
claim limitations):
19. A method for treating glabellar lines a condition in a
patient in need thereof, comprising:

[a] locally administering a first treatment of therapeutically
effective amount of a botulinum toxin composition
comprising a serotype A botulinum toxin in an amount
present in about 20 units of MT10109L, a first stabilizer
comprising a polysorbate, and at least one additional
stabilizer, and that does not comprise an animal-derived
product or recombinant human albumin;

[b] locally administering a second treatment of the
botulinum toxin composition at a time interval after the
first treatment;

[c] wherein said time interval is the length of effect of the
botulinum toxin composition as determined by
physician’s live assessment at maximum frown;

[d] wherein said botulinum toxin composition has a greater
length of effect compared to about 20 units of BOTOX®,
when whereby the botulinum toxin composition exhibits
a longer lasting effect in the patient when compared to
treatment of the same condition with a botulinum toxin
composition that contains an animal-derived product or
recombinant human albumin dosed at a comparable
amount and administered in the same manner for the
treatment of glabellar lines and to the same location(s) as
that of the botulinum toxin composition; and

[e] wherein said greater length of effect is determined by
physician’s live assessment at maximum frown and
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requires a responder rate at 16 weeks after the first
treatment of 50% or greater. that does not comprise an
animal-derived product or recombinant human albumin,
wherein the condition is selected from the group
consisting of glabellar lines, marionette lines, brow
furrows, lateral canthal lines, and any combination
thereof.
C. Level of Ordinary Skill in the Art
In the Petition, Petitioner proposes that a person of ordinary skill in
the art (“POSA”) “would have an advanced degree in biochemistry or
molecular biology with at least 5 years of experience in formulations
involving botulinum toxin and clinical studies involving such formulations.”
Pet. 10 (citing Ex. 1004 ¶ 14).
Patent Owner asserts that a POSA for the ’728 patent should include:
A person having a medical degree who practices dermatology,
aesthetic medicine, cosmetic surgery or other related
disciplines, and has been trained in and has experience with
administering botulinum toxin injections, including at least five
years of experience with injecting botulinum toxin formulations
and evaluating results of those treatments in patients or a person
with an advanced degree in biochemistry, molecular biology or
other related discipline with at least 5 years of experience in
protein compositions, such as botulinum toxins, and/or clinical
studies involving such compositions.
Rev. Mot. 2 (citing Ex. 2032 ¶ 62).
Patent Owner contends that the definition of a POSA must include
physicians “because the claims are primarily directed to physicians, whom
utilize the claimed methods of treatment, and have the most knowledge
regarding the prior art.” Id. Patent Owner notes that its expert Dr. Singh is a
physician “who has years of experience in administering neurotoxins [and]
understands the clinical significance of the claims and prior art,” whereas
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“Petitioner’s expert, Dr. Ramzan, is not a physician and has never treated
any patients with such toxins.” Id. at 2–3.
In our Institution Decision, we determined, based on the record at the
time, that a POSA would encompass the definition asserted by Petitioner.
Dec. 8. We maintain that determination based on the full evidence of record
adduced in this proceeding.
Factors that may be considered in determining level of ordinary skill
in the art include: (1) the educational level of the inventor; (2) type of
problems encountered in the art; (3) prior art solutions to those problems;
(4) rapidity with which innovations are made; (5) sophistication of the
technology; and (6) educational level of active workers in the field.
Orthopedic Equip. Co. v. All Orthopedic Appliances, Inc., 707 F.2d 1376 at
1381–82 (Fed. Cir. 1983).
We recognize that the claims are directed to methods of treatment, and
agree that a “clinician” or a “physician” may indeed have some relevant
experience implementing the claimed methods. But we are not persuaded
that the POSA must necessarily have a medical degree (M.D.) or be a
medical doctor to the extent that Patent Owner seeks to impose such
requirements on the POSA. In this regard, we note that none of the
inventors are physicians themselves. See Ex. 1059 ¶ 7 (recounting that
inventors Chang-Hoon Rhee and Gi-Hyeok Yang have PhDs, and inventor
Hyun Jee Kim has a Master’s degree in Pharmacy); Ex. 1050, 1; Ex. 1051,
1; Ex. 1052, 3. And although some of the publications of record appear to
be authored by individuals with medical degrees, we do not find that the
record suggests that being a physician is a prerequisite to working in the
field of botulinum toxins relevant to the claims. As such, even though
Petitioner’s expert, Dr. Ramzan, does not have a medical degree, we find
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that he is qualified to provide an opinion from the perspective of a POSA in
this proceeding based on his education and prior work experience in the field
and credit his testimony accordingly. See Ex. 1004 ¶ 5 (identifying
experience working on C. botulinum toxins, including work on
“approximately 6 products at various stages of clinical and commercial
development in the United States, Europe, and South Korea”).
D. Claim Construction
We interpret a claim “using the same claim construction standard that
would be used to construe the claim in a civil action under 35 U.S.C.
282(b).” 37 C.F.R. § 42.100(b) (2019). This standard requires that we
construe claims “in accordance with the ordinary and customary meaning of
such claim[s] as understood by one of ordinary skill in the art and the
prosecution history pertaining to the patent.” Id.
Patent Owner did not propose any claim constructions for the
substitute claims in its revised Motion. In its Opposition to the revised
Motion, Petitioner contends that “[t]he term ‘a serotype A botulinum toxin’
should be construed to mean ‘any serotype A botulinum neurotoxin,’
irrespective of whether it is in complexed or purified form and irrespective
of the size of the complex.” Opp. 1. Petitioner relies upon the definition for
“botulinum toxin” set forth in the ’728 patent as “a botulinum neurotoxin as
either pure toxin or complex, native, recombinant, or modified, and includes
botulinum toxin type A[.]” Id. (citing Ex. 1001, 4:21–23). Thus, Petitioner
contends that “the substitute claims encompass any serotype A botulinum
neurotoxin, including the 900 kDa complex known as onabotulinumtoxinA,
the mixture of 600 and 300 kDa complexes known as abobotulinumtoxinA,
and the purified, uncomplexed 150 kDa toxin known as
incobotulinumtoxinA.” Id. (citing Ex. 1094, 14:3–15). Patent Owner
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responds that “no construction is necessary as this term has a plain and
ordinary meaning that a POSA would understand, which both parties have
previously acknowledged.” Reply 1.
Upon review of the parties’ contentions, we determine that we need
not expressly construe “serotype A botulinum toxin” to resolve any disputed
issues of patentability for the proposed substitute claims. See Vivid Techs.,
Inc. v. Am. Sci. & Eng’g, Inc., 200 F.3d 795, 803 (Fed. Cir. 1999) (“[O]nly
those terms need to be construed that are in controversy, and only to the
extent necessary to resolve the controversy.”); see also Nidec Motor Corp. v.
Zhongshan Broad Ocean Motor Co., 868 F.3d 1013, 1017 (Fed. Cir. 2017)
(applying Vivid Techs. in the context of an inter partes review).
The parties also dispute whether the limitation requiring a responder
rate of “50 or greater” should be interpreted as a range of 50–100% (as
argued by Petitioner) or merely a minimum threshold of 50% (as argued by
Patent Owner). We address this issue as part of our analysis below.
E. Statutory and Regulatory Requirements
1. Reasonable Number of Substitute Claims
“There is a rebuttable presumption that a reasonable number of
substitute claims per challenged claim is one (1) substitute claim.”
Lectrosonics, Paper 15 at 4–5; 37 C.F.R. § 42.221(a)(3). Here, Patent
Owner’s revised MTA proposes nine substitute claims for nine of the
originally challenged claims. See Rev. Mot., App’x A. Thus, the revised
MTA complies with the requirement that the amendment propose a
reasonable number of substitute claims.
2. Responsive to Ground of Unpatentability
Patent Owner’s revised MTA responds to a ground of unpatentability
involved in this trial. See 37 C.F.R. § 42.221(a)(2)(i). In particular, Patent
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Owner’s claim amendments add features in an attempt to distinguish the
proposed substitute claims from the references as well as to address one or
more of the § 112 grounds asserted by Petitioner and/or addressed in our
Preliminary Guidance. Rev. Mot. 10–11; see Notice, 84 Fed. Reg. at 9,501
(“A revised MTA must provide amendments, arguments, and/or evidence in
a manner that is responsive to issues raised in the preliminary guidance (if
requested) or the petitioner’s opposition to the MTA.”).
3. No Enlargement of Claim Scope
“A motion to amend may not present substitute claims that enlarge the
scope of the claims of the challenged patent.” Lectrosonics, Paper 15 at 6–7;
35 U.S.C. § 326(d)(3); 37 C.F.R. § 41.221(a)(2)(ii).
Petitioner argues that proposed substitute claims 19 and 21–27
improperly broaden the claims beyond the original scope by eliminating the
phrase “dosed at a comparable amount” and introducing two new
requirements, namely that the botulinum toxin composition (1) contains the
same amount of neurotoxin as in about 20U MT10109L and (2) has a greater
length of effect compared to about 20U of BOTOX® (claim 19[a], [d]).
Opp. 2.
Petitioner contends that the “‘dosed at a comparable amount’
limitation in the original claims refers to a unit dose,” whereas “the
substitute claims have been rewritten to require the botulinum toxin be
administered in the same amount by weight of neurotoxin as is in 20U of
MT10109L, eliminating comparable unit doses and fundamentally
transforming the substitute claims.” Id. at 3–4.
To illustrate this point, Dr. Ramzan provides a comparison of three
botulinum neurotoxin products that were commercially available in the U.S.
(i.e., BOTOX®, DYSPORT®, and XEOMIN®). Ex. 1106 ¶¶ 31–38. Based
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on dose equivalency studies, Dr. Ramzan indicates that comparable unit
doses between the products are 50U of DYSPORT® to 20U of BOTOX®
and 20U of XEOMIN® to 20U of BOTOX®. Id. ¶ 27. And based on
published data from a peer-reviewed scientific journal measuring the mass
of 150 kDa neurotoxin in each of the products and an assumption that 20U
of MT10109L contains 0.17 ng of the 150 kDa neurotoxin protein, Dr.
Ramzan asserts that “to administer 0.17 ng of the neurotoxin in XEOMIN®,
one would need to inject 39U into a patient (or 0.17 ng multiplied by
100U/0.44 ng).” Id. ¶ 34. Thus, Dr. Ramzan opines, the 39U derived
applying a “by weight” calculation (like allegedly required in the substitute
claims) “is significantly higher than 20U of XEOMIN®, the dose equivalent
of 20U of BOTOX®” (like allegedly required applying the original claim
language). Id. Likewise, Dr. Ramzan asserts that “to administer 0.17 ng of
DYSPORT®, one would need to inject 26U into the patient (or 0.17 ng
multiplied by 100U/0.65,” which “is significantly lower than 50U of
DYSPORT®, the dose equivalent of 20U of BOTOX®.” Id. Dr. Ramzan
summarizes the comparison in the following chart:

Chart comparing “Comparable Dose” and “Same Amount By Weight”
for the products XEOMIN® and DYSPORT®
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The chart above indicates a +19U (+95%) dosing variance for
XEOMIN® and a -24U (-48%) dosing variance for DYSPORT® depending
on whether a “Comparable Dose” or “By Weight” methodology is used.
According to Petitioner and Dr. Ramzan, the large variances in the chart
above show that “there is no correlation between (i) the dose required to
administer the same amount by weight of neurotoxin in 20U of MT10109L
and (ii) the equivalent dose to 20U of BOTOX®.” Id. ¶ 35; Opp. 5–6.
Patent Owner responds that the amendment to remove the “dosed at a
comparable amount” was to address the Board’s concerns in the Preliminary
Guidance that the claims lack written description support in view of the fact
that the claims are not limited to administration of a 20 Units dose. Reply 2.
Patent Owner also contends that the amendment also addressed Petitioner’s
prior argument that “comparable amount” broadly covered “any animal
protein-free composition when dosed at any comparable amount of any
animal-protein containing composition.” Id. at 2–3. According to Patent
Owner, the claims now recite botulinum toxin compositions comprising a
specific amount—the amount of toxin present in about 20 units of
MT10109L—which is not broader than “any comparable amount.” Id. at 3.
We do not agree with Petitioner’s argument that the proposed
amendments are broader in scope than the original claims. Original claim 1
recites that “the botulinum toxin composition exhibits a longer lasting effect
in the patient when compared to treatment of the same condition with a
botulinum toxin composition that contains an animal-derived product or
recombinant human albumin dosed at a comparable amount.” Ex. 1001,
32:8–13. As noted by Petitioner, the comparison required by the original
claims was based on unit doses of an animal protein-containing botulinum
toxin composition and an animal-protein-free botulinum toxin composition
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as determined using an LD50 assay. Opp. 3. This was problematic
according to Petitioner insofar as each manufacturer uses its own proprietary
LD50 assay, and thus there was no uniform method by which those skilled in
the art could make the required comparison. Id. Proposed substitute
claim 19 now removes this ambiguity by reciting a composition with
serotype A botulinum toxin in an amount present in about 20 units of
MT10109L, and requiring a comparison of the length of effect of such a
composition with 20 units of BOTOX®.
Although the basis for the comparison has shifted from unit doses to
weight, we do not agree with Petitioner’s argument that this amendment
improperly broadens the claims’ scope. To the contrary, based on the record
here, Patent Owner persuades us that the amendment in question now
indicates a more specific amount of neurotoxin that falls within the scope of
the original claims—addressing Petitioner’s past criticisms and responding
to our concerns about unit dosing language of the earlier claims as explained
in the Preliminary Guidance. See Prelim. Guid. 6–7; Ex. 2072 ¶ 19 (noting 1
ng of a 900 kDa toxin complex, which includes the 150kDa toxin); Ex. 1106
¶ 34 (noting a 0.17 ng weight for the 150kDa serotype A toxin protein); Tr.
42:22–48:17 (discussing calculations to arrive at 0.17–0.18 nanograms of the
serotype A toxin). We find no sufficient and persuasive evidence of record
suggesting that the proposed substitute claims encompass a larger number of
compositions than the original claims.
Accordingly, we determine that the scope of each of the proposed
substitute claims is not improperly broader than the claim for which it is a
substitute.
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4. No New Matter
“A motion to amend may not present substitute claims that . . .
introduce new subject matter.” Lectrosonics, Paper 15 at 6–7; 35 U.S.C.
§ 326(d)(3); 37 C.F.R. § 41.221(a)(2)(ii). To evaluate compliance with the
prohibition on amendments that add new matter,
the Board requires that a motion to amend set forth written
description support in the originally filed disclosure of the
subject patent for each proposed substitute claim, and also set
forth support in an earlier filed disclosure for each claim for
which benefit of the filing date of the earlier filed disclosure is
sought.
Lectrosonics, Paper 15 at 7.
The revised MTA provides a chart listing purported written
description support in the originally filed disclosures of U.S. Patent
Application No. 15/336,119 (“the ’119 application”), U.S. Patent
Application 14/567,289, and Provisional U.S. Patent Application No.
61/915,476 for each of the proposed substitute claim limitations. Rev. Mot.
5–7.
Petitioner contends that proposed substitute claims 19–27 introduce
new matter by including the claimed “responder rate” limitation, i.e., the
requirement that “wherein said greater length of effect requires a responder
rate at 16 weeks after the first treatment of 50% or greater.” Opp. 12–16. In
its Opposition to the original Motion to Amend, Petitioner had previously
argued that the 16-week responder rate should be interpreted as a range of
50–100%. Paper 26, 3. In its Opposition to the revised MTA, Petitioner
now contends that this claim limitation lacks written description support
even under Patent Owner’s construction of “50% or greater” as requiring a
minimum threshold, rather than a range up to 100%. Opp. 12. Although
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Examples 1 and 2 in the ’728 patent’s specification provide 62% and 52%
responder rates for two specific formulations, Petitioner contends that
“unpredictability in the art would lead a POSA to conclude that the inventors
were only in possession of formulations exhibiting those specific 16-week
responder rates, not a minimum threshold of 50%.” Id. at 13. According to
Petitioner, Patent Owner “could have equally selected a minimum threshold
of 45%, which would encompass the responder rates of Examples 1 and 2
and is greater than the 16-week responder rates for 20U of BOTOX® in both
examples as originally defined in the specification,” and thus Patent Owner
is redefining how the specification expressly defines the “greater length of
effect” by now writing a 50% minimum threshold 16-week responder rate
requirement into the substitute claims. Id. at 14.
Petitioner further argues that there is no practical difference between
Patent Owner’s alleged “50% minimum threshold” construction and
Petitioner’s proposed range of “50-100%.” Id. In support of this contention,
Petitioner points to the deposition testimony of Patent Owner’s expert Dr.
Singh as acknowledging that compositions with 70%, 80%, and 90%
responder rates all meet Patent Owner’s minimum threshold of 50%. Id.
(citing Ex. 1089, 34:23–36:17). Petitioner asserts that Dr. Singh confirmed
that “it would be impossible to speculate . . . with any accuracy” how to
modify any of the formulations in the ’728 patent to achieve such higher
responder rates. Id. (citing Ex. 1089, 30:2–31:1).
In its Reply in support of the revised MTA, Patent Owner argues that
Petitioner mistakenly alleges that examples from the specification (showing
62% and 52% responder rates) are insufficient to support the 50% threshold
limitation. Reply 7. Citing In re Wertheim, 541 F.2d 257, 263 (CCPA
1976), Patent Owner contends that these examples provide sufficient written
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description support for the responder rate limitation because “there is no
requirement for exact correspondence between claim language and disclosed
embodiments.” Id. Patent Owner also notes that “Dr. Singh explains that a
50% responder rate is clinically meaningful to a POSA, especially
considering the use by others in the art of the 50% response rate to
determine efficacy of botulinum toxin to treat glabellar lines.” Id. (citing
Ex. 2062 ¶¶ 20–23).
Based on the record developed in this proceeding, we find that the
proposed substitute claims introduce new matter in the claimed “responder
rate” limitation. We recognize that in our Preliminary Guidance, we noted
based on the record at the time that we were not of the view that the
limitation should necessarily be interpreted as a range of 50–100%. Prelim.
Guide 5–6. However, the record has been further developed since we issued
our Preliminary Guidance. As noted by Petitioner, Patent Owner’s expert
Dr. Singh acknowledged during his deposition (taken after our Preliminary
Guidance issued) that the proposed substitute claims encompass responder
rates as high as 90%. Ex. 1089, 34:23–36:17. Patent Owner’s counsel
similarly acknowledged during the oral hearing that the proposed substitute
claims would read on higher responder rates, including up to 95%, but
continued to take the position that the claim limitation was intended to
impose only a minimum threshold of 50%. Tr. 62:6–20 (Patent Owner’s
counsel agreeing the claims encompass higher responder rates, such as 75%,
85%, and 95%); see also id. at 67:12–68:13 (Patent Owner’s counsel stating
that an interpretation of between 50–100% does not affect Patent Owner’s
argument). But even if the responder rate limitation was only intended to set
a “floor” rather than a “ceiling,” Patent Owner’s counsel acknowledged that
there will nonetheless be a natural upper limit of 100% for the claimed
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responder rate. Id. at 64:2–6 (“I think that you can’t have a responder rate
over 100 percent. . . . You can’t have more people respond than you have
patients.”); see also id. at 64:18–20 (“[I]nherently a person of skill in the art
looking at the specification would know you can’t exceed 100 percent.”).
An open-ended range would raise separate issues of indefiniteness and
enablement under 35 U.S.C. § 112. See MPEP § 2173.05(c) (II) (“Open-
ended numerical ranges should be carefully analyzed for definiteness.);
MagSil Corp. v. Hitachi Glob. Storage Techs., Inc., 687 F.3d 1377, 1383
(2012) (determining that claim term “change in the resistance by at least
10%” lacked enablement because it was interpreted to be an open-ended
range with no upper limit). As such, upon further consideration of the
record, we adopt Petitioner’s proposed construction and interpret the
limitation requiring a responder rate of “50% or greater” as a range of 50–
100%.
The test for determining compliance with the written description
requirement is not simply the presence or absence of literal support in the
specification for the claim language, but rather, whether the disclosure of the
application as originally filed reasonably conveys to a person of ordinary
skill in the art that the inventor had possession of the claimed subject matter
at the time of filing. Ariad Pharms., Inc. v. Eli Lilly & Co., 598 F.3d 1336,
1351 (Fed. Cir. 2010) (en banc); Vas-Cath, Inc. v. Mahurkar, 935 F.2d 1555,
1563 (Fed. Cir. 1991); In re Kaslow, 707 F.2d 1366, 1375 (Fed. Cir. 1983).
It is well settled that the written description requirement of § 112 requires
the disclosure to convey that Patent Owner had possession of the entire
range. In re Lukach, 442 F.2d 967, 969 (CCPA 1971) (holding that a single
disclosure of a value within a range does not provide support for the entire
range).
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It is undisputed that the phrase “50% or greater” does not appear in
the specification of the ’728 patent. Nonetheless, as purported written
description support for the responder rate limitation, Patent Owner provides
the following citations in the ’119 application (Ex. 1003) that issued as the
’728 patent and similar citations in the priority applications:
Citation Description
8:7–3 Provides a general description of the invention, noting that
“the animal-protein-free botulinum toxin composition
exhibits a longer lasting effectiveness compared to an
animal-protein-containing botulinum toxin composition”
when the patient was evaluated at 16 weeks.
15:12–16:7 Describes the time between the first and second treatments
of the animal-free botulinum toxin as ranging from one
month up to 52 weeks or more; notes that “[i]n certain
embodiments, the time between the first and second
treatment . . . is greater than 16 weeks for the effective
alleviation of at least one symptom.”
19:25–31 Notes that “[i]n certain embodiments, in a treatment method
of the invention, a therapeutically effective level botulinum
toxin is present in the recipient patient for an extended
period of time of at least 16 weeks” up to 50 weeks or more.
20:25–43:2 Broad citation to the Experimental Examples section
(Examples 1 and 2).
22:7–11 Describes the 16-week study design for Example 1, noting
that each subject received a 5 point intramuscular injection
with a total dose of 20U of MT10109L or BOTOX®.
23:6–15 Describes the “primary efficacy end point” of the study as
the percentage of responders at maximum frown at week 4
based on the investigator’s live assessment (face-to-face
observation). Further describes “secondary efficacy end
point” to include: 1) percentage of responders at maximum
frown at weeks 16; 2) percentage of responders of glabellar
lines at rest based on investigator’s 10 live assessment at
weeks 4 and 16; and 3) percentage of responders at
maximum frown and at rest based on photographic
assessment at week 4. Notes that “[i]n accordance with
previous studies for ona-BoNT/A, responders were defined
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Citation Description
as those who have post-treatment [Facial Wrinkle Scale
(FWS)] scores of 0 or 1 with pretreatment FWS scores of 2
or 3,” and “[t]his means an improvement of at least 1 point
for the subjects with moderate wrinkles and at least 2 points
for the 15 subjects with severe wrinkles.”
26:3–8 “The percentage of responders at maximum frown by live
assessment at weeks 16 was significantly lower in ona-
BoNT/A group than MT10109L group. The percentage of
responders in PP set was 62.34% in MT10109L group and
40.51% in ona-BoNT/A group (p value = 0.0064) (Table 3).
And the percentage of responders in FAS set was 60.71% in
MT10109L group and 41.67% in ona-BoNT/A group (Table
3, Figure 3B). Both PP set and FAS set showed significant
difference in two groups and superiority of MT10109L.”
32:29–33:8 Describes the Phase II study of Example 1, noting that
“[t]he results presented here compare the safety and efficacy
of lyophilized formulation of MT10109 and BOTOX® in
subjects with moderate to severe glabellar lines” and that it
was “demonstrated that the response at maximum frown
was sustained in the MT10109 20U group for up to 120
days.” Notes that the experiments compared dosing of
MT10109 at 10U, 20U and 30U to BOTOX® dosed at 20U
Further notes that the efficacy was primarily assessed at
Day 30 and “the comparison of interest was the comparison
between the responder rates for MT10109 20 U and
BOTOX® 20 U.” “A responder was defined as a glabellar
line severity rating of none (0) or mild (1) at maximum
frown or at rest at Day 30, depending on the analysis.”
36:14–37:4 “The proportion of responders at maximum frown decreased
in all treatment groups from Day 14 to Day 120 (based on
the investigator’s live assessment). The proportions at Day
120 were greater in the MT10109 20 U group compared
with BOTOX® 20 U and the other MT10109 groups
(Figure 6).”
“The proportion of responders at maximum frown in the
MT 10109 20 U group at Day 60, and at Day 120 was
65.2% (15 of 23 subjects) and 52.2% (12 of 23 subjects),
respectively, and in the BOTOX® 20 U group was 68.0%
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Citation Description
(17 of 25 subjects) and 23.1 % (6 of 26 subjects),
respectively (Table 9).”
Table 1 Identifies for Example 1 study “Scales to assess the
effectiveness of MT10109L and Ona-BonT/A.”
Table 3 Provides data from Example 1 study for “Responder rate by
live assessment at maximum frown.”
Table 9 Provides data from Example 2 study for “Investigator’s Live
Assessment Rating of Glabellar Line Severity at Other
Visits, Full Analysis Set.”

As indicted above, Patent Owner points to data included in the
specification showing 16-week responder rates of 52%, 61%, and 62%,
which are all greater than 50%. Ex. 1003, 26:3–8, 36:14–37:4. The issue is
whether these discrete data points support the full claimed range of
50–100%. We find that it does not. The disclosure and data in the
specification might support a method by which to achieve responder rates of
50% to about 62%, but this does not suggest—and the specification does not
describe—that the inventors were capable of achieving significantly higher
responder rates (up to 100%) using the MT10109L formulation. In this
regard, we note that the specification recognizes that responder rate
differences of about 20% between MT1019L and ona-BoNT/A were
considered to be “significant.” Id. at 26:7–8. A responder rate of, for
example, 82%, although it is encompassed by the claims and would
represent a “significant” result well beyond a 62% rate, is nowhere described
in the specification. As such, there is no basis to conclude that the inventors
were in possession of a method that could achieve a responder rate up to
38% higher than the highest responder rate described in the applications to
which the ’728 patent claims priority.
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The Wertheim case does not support Patent Owner’s position. In
Wertheim, the court considered whether there was sufficient written
description support in a foreign priority application for claim limitations
reciting a coffee solid content of “at least 35%” and “between 35% and
60%.” 541 F.2d at 261–62. The specification of the priority application
indicated that ground roasted coffee is concentrated prior to foaming by
suitable means “until a concentration of 25 to 60% solid matter is reached,”
while the examples disclosed embodiments having solids contents of 36%
and 50%. Id. at 262. The court found that this disclosure did not provide
written description support for the claims reciting “at least 35%” because
that limitation “reads literally on embodiments employing solids contents
outside the 25-60% range described in the Swiss application.” Id. at 263.
The court further noted that appellants did not meet their burden of showing
that the upper limit of solids content described, i.e., 60%, is inherent in “at
least 35%.” Id. at 264. The court, however, found that the claims reciting a
solid content range of “between 35% and 60%” presented a different
question because that claimed range fell within the broader described range
of 25% to 60% and was further supported by the specific example with a
solid content of 36%. Id. The court noted that:
In the context of this invention, in light of the description
of the invention as employing solids contents within the range of
25-60% along with specific embodiments of 36% and 50%, we
are of the opinion that, as a factual matter, persons skilled in the
art would consider processes employing a 35-60% solids content
range to be part of appellants’ invention and would be led by the
Swiss disclosure so to conclude.
Id. at 264.
We find that the written description issue in this case with respect to
the “50% or greater” responder rate limitation is analogous to the written
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description issue with respect to the “at least 35%” limitation addressed in
Wertheim. Indeed, there appears to be even less written description support
for the limitation here compared to Wertheim insofar as Patent Owner has
not identified the disclosure of a narrower range in the specification to
support the broader claimed responder rate range. Rather, Patent Owner has
identified only discrete 16-week responder rates of 52%, 61%, and 62%
from the examples, but we find that none of these examples would suggest
to a POSA that the inventors were in possession of a method that achieves
responder rates significantly higher than 62%, including up to 100%.
In Wertheim, the court also addressed a new matter rejection under
35 U.S.C. § 132 with respect to a claim limitation requiring that the frozen
foam be ground “to a particle size of at least 0.25 mm.” Id. at 265–66. As
noted by the court, the new matter rejection was “tantamount to a rejection
of the claims on the description requirement of 35 U.S.C. § 112, first
paragraph.” Id. at 265. Notwithstanding the specification’s indication of a
preferred particle size range of 0.25 to 2 mm, the court found that the “at
least 0.25 mm” limitation (with no upper limit) was supported by an
alternative embodiment disclosed in the specification in which freeze-dried
plates or lumps are subsequently ground to the desired particle size. Id. at
265–66. The court held that “[t]he clear implication of this disclosed
modification is that appellants’ specification does describe as their invention
processes in which particle size is ‘at least 0.25 mm,’ without upper limit, as
delineated by the rejected claims.” Id. at 266. As such, because the
inventive aspect of the limitation at issue in that case related to achieving
smaller particle sizes for the ground coffee, the court was not concerned
with the fact that there was no upper limit for the “at least 0.25 mm” particle
size claim limitation. We find this to be distinguishable from the “50% or
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greater” limitation at issue in this proceeding. In this case, there is no
indication in the specification that the inventors of the ’728 patent
contemplated achieving responder rates up to 100%. But even if that were
considered an implicit goal, the specification does not suggest that the
inventors were in possession of a method that would have achieved such
higher rates using the claimed animal-protein-free botulinum toxin
compositions. Cf. AbbVie Deutschland GmbH & Co. v. Janssen Biotech,
Inc., 759 F.3d 1285, 1300 (Fed. Cir. 2014) (holding insufficient a disclosure
that is “only a research plan, leaving it to others to explore the unknown
contours of the claimed genus”).
In sum, for the foregoing reasons, we find that the inclusion of the
“50% or greater” responder rate limitation impermissibly introduces new
subject matter into each of the proposed substitute claims. As such, Patent
Owner has not met the statutory and regulatory requirements for the revised
MTA.
F. Unpatentability Grounds
With regard to the proposed substitute claims, Petitioner also raises
multiple unpatentability grounds under 35 U.S.C. § 112 for lack of written
description support, lack of enablement, and indefiniteness. Opp. 7–25. As
it is dispositive to our conclusion, we focus our analysis on the written
description and enablement grounds with respect to the “50% or greater”
responder rate limitation.
1. Lack of Written Description
For the reasons we have discussed above with regard to the statutory
and regulatory prohibition against new matter, we also find the proposed
substitute claims are unpatentable under 35 U.S.C. § 112(a) for lack of
written description support. See Ariad, 598 F.3d at 1348 (noting that the
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prohibition against “adding new matter to the claims has properly been held
enforceable under § 112, first paragraph”).
2. Lack of Enablement
Petitioner separately argues that the proposed substitute claims are not
enabled with respect to the “50% or greater” limitation. In assessing
whether the claims satisfy the enablement requirement of 35 U.S.C.
§ 112(a), we consider the so-called “Wands factors”: (1) the quantity of
experimentation necessary, (2) the amount of direction or guidance
presented, (3) the presence or absence of working examples, (4) the nature
of the invention, (5) the state of the prior art, (6) the relative skill of those in
the art, (7) the predictability or unpredictability of the art, and (8) the breadth
of the claims. In re Wands, 858 F.2d 731, 737 (Fed. Cir. 1998).
With respect to the quantity of experimentation necessary, Petitioner
contends that:
Given Dr. Singh’s admission that substantial changes in
excipients and neurotoxin can make it impossible to speculate
whether a certain formulation would meet the claimed 50%
threshold responder rate, a clinical study would need to be
conducted for any formulation in which an excipient or the
neurotoxin was changed, amounting to a research plan of trial
and error.
Opp. 17 (citing Ex. 1106 ¶ 86); see also id. at 14 (citing Ex. 1089, 30:2–
31:1, where Dr. Singh acknowledged that if you changed some of the
formulation components, including the type of botulinum toxin A, it would
be “impossible to speculate” whether the formulation would exhibit or meet
the 50% responder rate limitation). As further evidence of the high amount
of experimentation necessary, Petitioner points out that the substitute claims
encompass formulations that contain abotulinumtoxinA, which requires a
dose of 2.5 times the dose of 20U of BOTOX®, and thus “substantial
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development work would be necessary to achieve the threshold responder
rate with such a low dose of abobotulinumtoxinA.” Id. at 17 (citing Ex.
1106 ¶ 87).
With respect to the amount of direction provided in the specification,
Petitioner contends that “[t]he specification describes clinical data for
MT10109 (in liquid and lyophilized forms) but does not teach a POSA how
to modify MT10109 by changing the neurotoxin, the polysorbate, or the
other stabilizer while still maintaining the threshold 16-week responder
rate.” Id. at 18 (citing Ex. 1106 ¶ 89).
With respect to the presence or absence of working examples,
Petitioner contends that the specification provides only two working
examples that exhibit very specific responder rates (52% and 62%) “tied to
the specific formulations in a specific patient population.” Id. (citing
Ex. 1106 ¶ 90).
With respect to the nature of the invention and the state of the prior
art, Petitioner contends that “[a]t the time of the ’728 patent, there was
nothing that would permit a POSA to correlate the formulation of any
botulinum toxin composition with a 16-week responder rate of 50% or
greater” and thus “the 16-week responder rate could only be determined by
conducting a costly and expensive clinical trial.” Id. at 18–19 (citing
Ex. 1106 ¶¶ 91–92).
With respect to the relative skill of those in the art and predictability
in the art, Petitioner contends that the parties agree that the level of skill in
the art is relatively high, but contends that achieving the claimed 16-week
responder rates is unpredictable. Id. at 19 (citing Ex. 1106 ¶¶ 93–94).
Finally, with respect to the breadth of the claims, Petitioner contends
that the proposed substitute claims are “so broad that they include a large
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number of potential botulinum toxin A compositions, but the specification
provides no guidance as to which ones would exhibit the claimed ‘greater
duration of effect’ (as measured by responder rates at 16 weeks using
physician’s live assessment) and which ones would not.” Id. (citing Ex.
1106 ¶¶ 97–101). Petitioner points to Dr. Ramzan’s testimony explaining
that the “the teachings of the ’728 patent do not establish any structure-
function correlation between the ingredients (or their amounts) of a
botulinum toxin A composition and its 16-week responder rate.” Id.
at 19–20. Petitioner also contends the ’728 patent does not teach a person of
ordinary skill in the art how to formulate any abobotulinum A neurotoxin
composition that exhibits the claimed responder rate when administered in
the same amount as 20U of BOTOX®.” Id. at 21.
Patent Owner responds that the revised proposed substitute claims are
enabled because Petitioner relies upon “the flawed proposition that clinical
studies categorically require undue experimentation, while mischaracterizing
the abilities of a POSA.” Reply 9. According to Patent Owner, “[i]t would
take no more than routine experimentation to confirm that similarly
formulated toxin compositions meet the claimed duration limitation.” Id. at
10 (citing Ex. 2062 ¶¶ 28–32). Patent Owner relies upon the testimony of its
expert Dr. Middaugh as explaining “that in view of the disclosure of the
’728 Patent, a POSA would expect other similar formulations containing
polysorbate and a stabilizer to have a similarly greater length of effect
compared to BOTOX®.” Id. Patent Owner also contends that Petitioner’s
arguments are flawed insofar as the Federal Circuit does not require working
examples to satisfy the enablement requirement and that such arguments rest
on the mistaken premise that the claims require comparability between the
claimed composition and 20U of BOTOX®. Id. at 11. Additionally, with
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regard to proposed substitute claim 20 in particular, Patent Owner contends
that a POSA would be able to replicate MT10109L without knowledge of
Patent Owner’s proprietary manufacturing process.” Id. at 11–12.
Having considered the arguments and evidence of record, we
determine that a preponderance of the evidence supports the conclusion that
the full scope of the claims is not enabled. In particular, Petitioner has
persuasively shown through the testimony of its expert Dr. Ramzan that,
based on the guidance provided in the specification, a POSA would not have
been able to achieve responder rates significantly higher than the
exemplified 62% responder rate, including as high 85%, 95%, or even
100%, using the claimed animal-protein-free botulinum toxin formulations
without undue experimentation. Ex. 1106 ¶¶ 85–101.
We find the Magsil case to be instructive. There, the court held that
the claims were not enabled with respect to a limitation reciting “a change in
the resistance by at least 10% at room temperature” when the specification
only taught that the inventors were able to achieve a maximum change in
resistance of 11.8%. Magsil, 687 F.3d at 1379–85. The court found that the
specification only enabled an ordinarily skilled artisan to achieve a small
subset of the claimed range, and the “[t]he open claim language chosen by
the inventors does not grant them any forgiveness on the scope of required
enablement.” Id. at 1383–84.
Likewise, in In re Fisher, the court held that claims reciting an
open-end range of a potency of “at least 1 International Unit of ACTH per
milligram” were not enabled by a specification disclosing products having
potencies from 1.11 to 2.30 International Units. 427 F.2d 833, 839 (CCPA
1970). The court in Fisher noted that:
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The issue thus presented is whether an inventor[] who is the
first to achieve a potency of greater than 1.0 for certain types of
compositions, which potency was long desired because of its
beneficial effect on humans, should be allowed to dominate all
such compositions having potencies greater than 1.0, including
future compositions having potencies far in excess of those
obtainable from his teachings plus ordinary skill.
Id. The court concluded “that appellant has not enabled the preparation of
ACTHs having potencies much greater than 2.3, and the claim recitations of
potency of ‘at least 1’ render the claims insufficiently supported under the
first paragraph of 35 U.S.C. § 112.” Id. Here, unlike the open-ended ranges
at issue in Magsil and Fisher, we have interpreted the responder rate
limitation to have an upper limit of 100%. But even with that bounded
interpretation, we find nothing in the specification to suggest that a POSA
would, absent undue experimentation, have been able to achieve responder
rates much higher than the maximum responder rate of 62% disclosed in the
examples of the ’728 patent.
Although Patent Owner has argued that the claims are enabled with
regard to other limitations, Patent Owner does not address the enablement
arguments made with regard to the full scope of the responder rate limitation
when it is interpreted to be a range of 50–100%. Rather, Patent Owner’s
arguments are based on the assumption that the responder rate limitation
only requires a threshold of 50%, which we have rejected for the reasons
stated above.
Accordingly, we conclude that the proposed substitute claims are
unpatentable for lack of enablement under 35 U.S.C. § 112(a).
III. CONCLUSION
For the foregoing reasons, we conclude that Patent Owner has not met
its burden of meeting the statutory and regulatory requirement against
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introducing new matter in the proposed substitute claims. Additionally, we
determine that Petitioner has demonstrated by a preponderance of the
evidence that the proposed substitute claims are unpatentable under
35 U.S.C. § 112(a) for lack of written description support and lack of
enablement.3 Accordingly, we deny Patent Owner’s revised Motion to
Amend with regard to proposed substitute claims 19–27.4 Original claims
1–10 of the ’728 patent are cancelled by virtue of Patent Owner’s non-
contingent revised MTA.
In summary:
Motion to Amend Outcome Claim(s)
Original Claims Cancelled by Amendment 1–10
Substitute Claims Proposed in the Amendment 19–27
Substitute Claims: Motion to Amend Granted
Substitute Claims: Motion to Amend Denied 19–27
Substitute Claims: Not Reached

IV. ORDER
In consideration of the foregoing, it is hereby:

3 In view of our conclusion with regard to the “50% or greater” limitation,
we do not reach the other unpatentability arguments with regard to the
proposed substitute claims, including the sua sponte ground of
unpatentability that we asked the parties to address at oral argument.
4 Should Patent Owner wish to pursue amendment of the challenged claims
in a reissue or reexamination proceeding subsequent to the issuance of this
decision, we draw Patent Owner’s attention to the April 2019 Notice
Regarding Options for Amendments by Patent Owner Through Reissue or
Reexamination During a Pending AIA Trial Proceeding. See 84 Fed. Reg.
16,654 (Apr. 22, 2019). If Patent Owner chooses to file a reissue application
or a request for reexamination of the challenged patent, we remind Patent
Owner of its continuing obligation to notify the Board of any such related
matters in updated mandatory notices. See 37 C.F.R. § 42.8(a)(3), (b)(2).

PGR2019-00062
Patent 10,143,728 B2
35
ORDERED that original claims 1–10 of the ’728 patent are cancelled
by virtue of Patent Owner’s non-contingent revised Motion to Amend;
FURTHER ORDERED that Patent Owner’s non-contingent revised
Motion to Amend is denied as to proposed substitute claims 19–27; and
FURTHER ORDERED that, because this is a final written decision,
parties to this proceeding seeking judicial review of our Decision must
comply with the notice and service requirements of 37 C.F.R. § 90.2.
PGR2019-00062
Patent 10,143,728 B2
36
FOR PETITIONER:
Joseph Mahoney
Amanda Bonner
Erick Palmer
MAYER BROWN LLP
jmahoney@mayerbrown.com
astreff@mayerbrown.com
ejpalmer@mayerbrown.com

FOR PATENT OWNER:
Dominick Conde
VENABLE LLP
dconde@venable.com