Date

March 25, 2016

Case number

2015 (Ne) 10014

Court

Intellectual Property High Court,
Special Division– A case in which, with regard to a manufacturing process of a preparation, etc., thecourt upheld a claim for an injunction against the import and sale of the preparation,etc. and other claims based on a patent right on the grounds that said process isequivalent to a patented invention.
– A case in which the court ruled as follows: The essential part of a patented invention
in the first requirement of the doctrine of equivalents means a characteristic part,which constitutes a unique technical idea that is not seen in prior art, in the statementsin the scope of claims of the patented invention, and the essential part should be foundbased on the statements in the scope of claims and the description, in particular, thecomparison with prior art stated in the description and the degree of contribution.
– A case in which the court ruled as follows: The fact that the applicant did not state
another structure, which a person ordinarily skilled in the art can easily conceive of as
of the filing date as one that is substantially identical with the structure stated in thescope of claims, in the scope of claims only because of the existence of such otherstructure cannot be considered to fall under the "special circumstances" in the fifth
requirement of the doctrine of equivalents; however, if the applicant is objectively andexternally recognized as having recognized another structure that is outside the scopeof claims as a replacement for a different part in the structure stated in the scope ofclaims as of the filing date, the applicant's failure to state said other structure in thescope of claims can be considered to fall under the "special circumstances" in the fifth
requirement of the doctrine of equivalents.
Reference: Article 100, paragraphs (1) and (2), Article 70, paragraph (1), and Article 29,
paragraph (2) of the Patent Act
Number of related rights, etc.: Patent No. 3310301 (the "Patent"), Invalidation Trial No.
2013-800080
Summary of the judgment
1. Background
The appellee (plaintiff in the first instance), who holds the patent right in question(the "Patent Right") for an invention titled "intermediates for the synthesis of vitamin D
and steroid derivatives and process for preparation thereof," alleged that the
manufacturing process (the "Appellant's Process") of the maxacalcitol preparations, etc.
(the "Appellants' Products") imported and sold by the appellants (defendants in the first
instance) is equivalent to the invention claimed in Claim 13 of the Patent (thei"Corrected Invention") and that the sale, etc. of the Appellants' Products constitutes
infringement of the Patent Right. Based on this allegation, the appellee filed this action
against the appellants to seek an injunction against the import, assignment, etc. of theAppellants' Products and disposal thereof.
Briefly speaking, the Corrected Invention is a process for preparing a compound
wherein an intermediate is prepared by having the starting material react with a
specific reagent and the objective substance is prepared by treating the intermediatewith a reducing agent. The Appellant's Process fulfills the constituent features
pertaining to the reagent and objective substance of the Corrected Invention(Constituent Features [A], [B-2], [D], and [E]), but does not fulfill the constituent
features pertaining to the starting material and intermediate of the Corrected
Invention (Constituent Features [B-1], [B-3], and [C]) in that the carbon skeletons of thestarting material and the intermediate do not have cis-form vitamin D structures but
have trans-form vitamin D structures that are the geometric isomers thereof.
In relation to the doctrine of equivalents, the five requirements for applying thedoctrine of equivalents are indicated in the judgment of the Third Petty Bench of theSupreme Court of February 24, 1998, 1994 (O) 1083 ("Ball spline bearing" case). In thiscase, the parties disputed whether the doctrine of equivalents is established throughspecific application of the five requirements. In addition, the appellants alleged that the
Patent should be invalidated by a trial for patent invalidation.
The court of prior instance recognized that the Appellant's Process is equivalent to
the Corrected Invention and determined that the patent for the Corrected Invention is
not recognized as one that should be invalidated by a trial for patent invalidation.
Based thereon, the court of prior instance upheld all of the appellee's claims. Therefore,dissatisfied with this, the appellants filed an appeal (the "Appeal").
2. Content of this judgment
In this judgment, the court ruled as summarized below, and recognized that theAppellant's Process is equivalent to the Corrected Invention. The court also determinedthat there is no reason for all of the grounds for invalidation alleged by the appellants.
Based thereon, the court upheld the judgment in prior instance and dismissed the
Appeal.
(1) Regarding the burden of proving the fulfillment of the five requirements for thedoctrine of equivalents"Regarding the burden of alleging and proving the fulfillment of the first to fifth
requirements, it is reasonable to understand as follows, taking into account that thedoctrine of equivalents should be applied within the scope of those that are found to beii

easily conceived of by a person ordinarily skilled in the art as one that is substantially
identical with the statements in the scope of claims beyond the scope of the literalinterpretation of said statements: a person who alleges that the subject product, etc. isequivalent to a patented invention should be considered to have the burden of allegationand proof for the first to third requirements, which are the facts required for the subject
product, etc. to be recognized as falling within said scope, while a person who denies theapplication of the doctrine of equivalents in relation to the subject product, etc. has theburden of allegation and proof for the fourth and fifth requirements, which are related
to the cases where the application of the doctrine of equivalents should be eliminated,even if the subject product, etc. is within the aforementioned scope."(2) Regarding the first requirement of the doctrine of equivalents (non-essential part)
The first requirement of the doctrine of equivalents in the Supreme Court judgmenton the "Ball spline bearing" case is that even if the structure stated in the scope ofclaims contains any part that is different from that of the product manufactured, etc. by
the other party or the process used thereby, said part is not the essential part of thepatented invention.
A. "The substantial value of an invention which the Patent Act intends to protect exists
in the disclosure, with a specific structure, to society of a means for solving a technicalproblem that could not have been solved by prior art, which is based on a unique
technical idea that is not seen in prior art. Therefore, the essential part of a patented
invention should be understood as the characteristic part which constitutes a unique
technical idea that is not seen in prior art in the statements in the scope of claims of thepatented invention.
The aforementioned essential part should be found by first understanding the
problem to be solved and means for solving the problem of the patented invention …
and its effects … based on the statements in the scope of claims and the description andthen determining the characteristic part that constitutes a unique technical idea that is
not seen in prior art in the statements in the scope of claims of the patented invention.
That is, taking into account that the substantial value of a patented invention is defined
depending on the degree of contribution in comparison with prior art in the relevant
technical field, the essential part of a patented invention should be found based on thestatements in the scope of claims and the description, in particular, through comparison
with prior art stated in the description. [i] If the degree of contribution of the patented
invention is considered to be more than that of prior art, the patented invention is foundas a generic concept in relation to part of the statements in the scope of claims …. [ii] If
the degree of contribution of the patented invention is evaluated as not much more thaniii

prior art, the patented invention is found to have almost the same meaning as stated in
the scope of claims.
However, if the statement of the problem, which is described as one that prior art
could not solve, in the description is objectively insufficient in light of prior art as of thefiling date …, a characteristic part which constitutes a unique technical idea of thepatented invention that is not seen in prior art should be found also in consideration ofprior art that is not stated in the description. In such cases, the essential part of thepatented invention is closer to the statements in the scope of claims compared to thecases where it is found only based on the statements in the scope of claims and thedescription, and the scope of application of the doctrine of equivalents is considered tobe narrower.
In addition, in determining the fulfillment of the first requirement, that is, whether
a difference from the subject product, etc. is a non-essential part, it is not appropriate to
first divide the constituent features stated in the scope of claims into essential parts andnon-essential parts and then consider that the doctrine of equivalents is not applicable
to all of the constituent features that fall under essential parts, but it is necessary to
first determine whether the subject product, etc. commonly has the essential part of thepatented invention determined as mentioned above and then consider a difference not
to be an essential part if the subject product, etc. is recognized as having said essential
part. Even if the subject product, etc. has a difference other than the characteristic partthat constitutes a unique technical idea that is not seen in prior art, this fact does not
become a reason for denying the fulfillment of the first requirement."
B. "The Corrected Invention makes it possible to prepare its objective substancethrough a new preparation route that is not available in prior art, and its degree ofcontribution to prior art is large. … The Corrected Invention made it possible toindustrially produce maxacalcitol for the first time. …
In light of the problem to be solved and means for solving the problem of theCorrected Invention and its effects as mentioned above, the essential part of theCorrected Invention … is recognized as existing in finding that a side chain having an
epoxy group by an ether bond can be introduced through one step by having an alcoholcompound at position 20 of a vitamin D structure or steroid ring structure react with an
epoxy hydrocarbon compound of Constituent Feature [B-2] which has an eliminatinggroup at its end and in making it possible to introduce a maxacalcitol side chain into an
alcohol compound at position 20 of a vitamin D structure or steroid ring structure
through a new route of first going through an intermediate that is a vitamin D structure
or steroid ring structure into which a side chain having an epoxy group by an ether bondiv

is introduced through such one step and then opening the ring of the epoxy group of theside chain. …
The Appellant's Process … is considered to have the characteristic part that
constitutes a unique technical idea that is not seen in prior art in the statements in thescope of claims of the Corrected Invention.
On the other hand, in the Appellant's Process, the point that a vitamin D structurethat corresponds to "Z" of the starting material and the intermediate, which is adifference from the Corrected Invention, is not a cis form but a trans form … is not theessential part of the Corrected Invention.
Therefore, the Appellant's Process is recognized as fulfilling the first requirement of
the doctrine of equivalents."(3) Regarding the second requirement of the doctrine of equivalents (replaceability)"In … Starting Material A and Intermediate C in the Appellant's Process, the carbon
skeleton that corresponds to Z of the Corrected Invention is a trans-form vitamin D
structure, and the Appellant's Process differs from the Corrected Invention in that the
carbon skeleton of Z of the starting material … and intermediate … in the Corrected
Invention is a cis-form vitamin D structure. However, the starting materials andintermediates in both the Appellant's Process and the Corrected Invention have thesame function and effect of being able to prepare maxacalcitol by a process of going
through an intermediate that is a vitamin D structure into which a side chain having an
epoxy group by an ether bond through one step by having an alcohol compound at
position 20 of a vitamin D structure react with the same epoxy hydrocarbon compound.
It is recognized that the same purpose as that of the Corrected Invention can beachieved and the same function and effect are produced even if the aforementioned
starting material and intermediate having a cis-form vitamin D structure in the
Corrected Invention are replaced with the aforementioned starting material andintermediate having a trans-form vitamin D structure in the Appellant's Process. …
Therefore, the Appellant's Process is recognized as fulfilling the second requirement of
the doctrine of equivalents."(4) Regarding the third requirement of the doctrine of equivalents (easiness of
replacement)
In this judgment, the court determined that the Appellant's Process is one that aperson ordinarily skilled in the art could have easily conceived of based on the Corrected
Invention as of the time of infringement of the Patent Right and found that theAppellant's Process fulfills the third requirement of the doctrine of equivalents.
(5) Regarding the fourth requirement of the doctrine of equivalents (whether the subjectv

process can be easily presumptively conceived of)In this judgment, regarding the fourth requirement of the doctrine of equivalents,
the court cited the judgment in prior instance and determined that the Appellant's
Process is not recognized as one that can be easily presumptively conceived of.
(6) Regarding the fifth requirement of the doctrine of equivalents (special
circumstances)
The fifth requirement of the doctrine of equivalents mentioned in the Supreme Court
judgment on the "Ball spline bearing" case is that there are no special circumstances,such as the fact that the subject product, etc. falls under those that are intentionally
excluded from the scope of claims in the patent application procedures for the patented
invention.
A. "The substantial value of a patented invention extends to the art which a person
ordinarily skilled in the art can easily conceive of based on the structure stated in thescope of claims as one that is substantially identical with said structure, and third
parties should expect this. Therefore, if the subject product, etc. is identical with apatented invention in the essential part, purpose, and function and effect, and is one
that a person ordinarily skilled in the art can easily conceive of based on the patented
invention, the subject product, etc. can be in principle considered to be equivalent to thepatented invention. However, with regard to a structure which was once approved by
the patentee as not falling under the technical scope of the patented invention (forexample, in the case where the applicant intentionally excluded it from the scope ofclaims in the patent application procedures) or for which the patentee has taken actionthat is externally considered as such approval, the patentee is not permitted tosubsequently make an allegation that goes against said approval or action in light of thedoctrine of estoppel. Therefore, if there are such special circumstances, the applicationof the doctrine of equivalents is exceptionally denied (see the aforementioned Supreme
Court judgment on the "Ball spline bearing" case).
(A) In this regard, even if there is another structure that is outside the scope of claims,
which a person ordinarily skilled in the art can easily conceive of as of the filing date as
one that is substantially identical with the structure stated in the scope of claims andthe applicant could thus have also easily conceived of said another structure as of thefiling date, this fact alone cannot serve as a reason for alleging that the applicant's
failure to state said another structure in the scope of claims falls under the "special
circumstances" in the fifth requirement of the doctrine of equivalents.
This is because of the following reasons. [i] As mentioned above, the substantial
value of a patented invention extends to the art that a person ordinarily skilled in theviart can easily conceive of as one that is substantially identical with the structure statedin the scope of claims based on said structure even if it is a structure other than the
structure stated in the scope of claims. This principle does not change at all in relation
to any art that a person ordinarily skilled in the art can easily conceive of as of the filingdate. If it is not at all permitted to allege the doctrine of equivalents only for the reason
that a structure could have been easily conceived of by a person ordinarily skilled in theart as of the filing date, the scope to which the substantial value of a patented invention
extends will differ from the aforementioned scope. [ii] In addition, taking into accountthat an applicant should first disclose his/her invention to the public by stating it in thedescription and then clearly specify the scope of the exclusive right in the scope ofclaims, the applicant should state the scope of claims in just proportion within the scopeof the invention disclosed in the description while fulfilling the requirements, such as
the support requirements under Article 36, paragraph (5) of the Patent Act andparagraph (6), item (i) of said Article and the clarity requirements under item (ii) of said
paragraph. However, in some cases, it is considered to be harsh to require the applicant
to prepare the scope of claims that contains all the expected infringing embodiments
and the description supporting such scope of claims within a limited period of time,taking into account the fact that, under the first-to-file system, applicants are generally
required to prepare the scope of claims and the description and file applications within alimited period of time. On the other hand, in many cases, a third party who has received
the disclosure of an invention as described in the description pertaining to a patentapplication can easily conceive of one which has the essential part of the patented
invention but part of which is not included in the literal interpretation of the scope ofclaims, based on the statements in the scope of claims and the description, etc., during
the duration of the patent. The doctrine of equivalents is applicable because if any third
party can easily escape from the exercise of rights by the patentee, including an
injunction, through replacement of the non-essential part of the patented invention,
incentive to invent in society in general will be diminished, which not only goes against
the purpose of the Patent Act, that is, contributing to the development of industry
through protection and encouragement of inventions, but also goes against social justiceand results in running counter to the principle of equity. In light of the aforementioned
situation, etc., even if a person ordinarily skilled in the art could have easily conceivedof another structure that is outside the scope of claims as of the filing date, it is notreasonable to exclude said another structure from the application of the doctrine ofequivalents only for the reason of such fact without exception.
(B) However, even in such a case, if the applicant is objectively and externallyvii

recognized as having recognized another structure that is outside the scope of claims as
a replacement for a different part in the structure stated in the scope of claims as of thefiling date (for example, where the applicant can be considered to have stated theinvention based on said another structure in the description or where the applicant
stated the invention based on another structure that is outside the scope of claims in apaper, etc. which he/she published as of the filing date), the applicant's failure to state
said another structure in the scope of claims is considered to fall under the "special
circumstances" in the fifth requirement.
The reason therefor is as follows. In the aforementioned cases, it can be understoodthat the patentee intentionally excluded said another structure from the scope of claims
when stating the scope of claims, that is, the patentee approved that said anotherstructure does not fall under the technical scope of the patented invention or took actionthat is externally understood as such approval, and the trust of a third party who
understands as such should be protected. Therefore, the patentee is not permitted tosubsequently allege the application of the doctrine of equivalents in relation to thesubject product, etc. that is based on said another structure in contradiction to suchprotection in light of the doctrine of estoppel."
B. In this judgment, the court specifically considered the statements, etc. in thecorrected description, which the appellants allege as the "special circumstances" in thefifth requirement, and determined as follows: The corrected description does not include
any statement that can be considered to be stating an invention wherein the starting
material of the Corrected Invention has a trans-form vitamin D structure, and there isno other evidence sufficient to objectively and externally recognize that the applicant
recognized a trans-form vitamin D structure as a replacement for a cis-form vitamin D
structure as the starting material of the Corrected Invention as of the filing date of theapplication for the Patent; therefore, the special circumstances in the fifth requirementof the doctrine of equivalents cannot be recognized.
(6) Regarding the existence or absence of grounds for invalidation of the Corrected
Invention
In this judgment, the court determined that all of the grounds for invalidation
alleged by the appellants are unacceptable.

viii

Judgment rendered on March 25, 20162015 (Ne) 10014 Appeal Case of Seeking Injunction against Patent Right Infringement(the court of prior instance: Tokyo District Court, 2013 (Wa) 4040)
Date of conclusion of oral argument: February 19, 2016
Judgment
Appellant: DKSH Japan K.K.
(Hereinafter referred to as "Appellant DKSH")
Appellant: Iwaki Seiyaku Co., Ltd.
(Hereinafter referred to as "Appellant Iwaki Seiyaku")
Appellant: Takata Pharmaceutical Co., Ltd.
(Hereinafter referred to as "Appellant Takata Pharmaceutical")Appellant: Pola Pharma Inc.
(Hereinafter referred to as "Appellant Pola Pharma")Counsel attorney for the aforementioned four appellants:
SHINBO Katsuyoshi
Same as above: TAKASAKI Jin
Same as above: HORA Takashi
Same as above: INOUE Akira
Same as above: SAKO Teiyu
Counsel patent attorney for the aforementioned four appellants:
MAMURA Masazumi
Same as above: WATANABE ShihoCounsel patent attorney as an assistant in court for the
aforementioned four appellants: MUROFUSHI Yoshinobu
Same as above: INOUE Kaori
Appellee: Chugai Pharmaceutical Co., Ltd.
Counsel attorney: OZAKI Hideo
Same as above: HINO EiichiroSame as above: EGURO Sayaka
Main text
1. All of the appeals in question shall be dismissed.
2. The appellants shall bear the cost of the appeal.
Facts and reasonsNo. 1 Object of the appeal

11. The judgment in prior instance shall be revoked.
2. All of the appellee's claims shall be dismissed.
No. 2 Outline of the case
1. In this case, the appellee is one of the joint owners of the patent right for an invention
titled "intermediates for the synthesis of vitamin D and steroid derivatives and process
for preparation thereof" (Patent No. 3310301; hereinafter, said patent right is referred toas the "Patent Right"; the patent pertaining to the Patent Right is referred to as the"Patent"). The appellee alleges that the process described in the Process List attached tothis judgment (hereinafter referred to as the "Appellant's Process"), which is the process
for the preparation of the maxacalcitol active pharmaceutical ingredient described in
Item List 1 attached to the judgment in prior instance (hereinafter referred to as"Appellant's Product 1"), which is imported and sold by Appellant DKSH, and the
maxacalcitol preparations described in (1) to (3) in Item List 2 attached to the judgmentin prior instance, which are sold by Appellant Iwaki Seiyaku, Appellant Takata
Pharmaceutical, and Appellant Pola Pharma, respectively (hereinafter, each of said
maxacalcitol preparations is independently referred to as "Appellant's Product 2(1)," etc.,
and are collectively referred to as "Appellants' Products 2"; these preparations andAppellant's Product 1 are collectively referred to as "Appellants' Products"; incidentally,
Appellant's Product 1 is identified as having been prepared by the Appellant's Process in
Item List 1 attached to the judgment in prior instance, and Appellants' Products 2 are
identified as maxacalcitol preparations prepared by the Appellant's Process in Item List
2 attached to the judgment in prior instance), are equivalent to and fall under thetechnical scope of the invention claimed in Claim 13 (hereinafter referred to as the"Invention") in the scope of claims in the description pertaining to the Patent (thedescription as of the registration of establishment of the Patent Right; hereinafter,
referred to as the "Description"; incidentally, as the Patent pertains to an application
filed before June 30, 2003, the Description includes the scope of claims [Article 1, item(ii) and Article 3, paragraph (1) of the Supplementary Provisions of Act No. 24 of 2002
and Cabinet Order No. 214 of 2003]). Based on this allegation, the appellee demands
that [i] Appellant DKSH suspend the import and assignment of Appellant's Product 1
until September 3, 2017 and dispose of it, and that [ii] all the other appellants suspend
the assignment and offer for assignment of Appellants' Products 2(1) to (3), respectively,
until the same date and dispose of them, under Article 100, paragraphs (1) and (2) of the
Patent Act. Incidentally, the appellee corrected Claim 13 in the scope of claims by awritten request for correction dated September 25, 2013 in a trial for patent invalidation
for the Patent after filing this action.

2

The court of prior instance recognized that the Appellant's Process is equivalent to
the Invention and the invention claimed in Claim 13 in the scope of claims after the
aforementioned correction (hereinafter referred to as the "Corrected Invention"), andalso determined that the patent pertaining to the Invention is not recognized as one thatshould be invalidated by a trial for patent invalidation. Based thereon, the court of priorinstance upheld all of the appellee's claims. Therefore, dissatisfied with the judgment inprior instance, the appellants (defendants in prior instance) filed this appeal.
In the proceedings in this instance, a JPO decision accepting the aforementioned
correction became final and binding.
2. Facts on which the decision is premised (facts undisputed by the parties or facts thatcan be easily found by the evidence described in the text and the entire import ofargument)(1) Parties
A. The appellee is a stock company engaging in the business of research, development,
preparation, sale, and import and export, etc. of medicines.
B. Appellant DKSH is a stock company engaging in the business of import, sale, etc. of
medicines.
C. Each of Appellant Iwaki Seiyaku, Appellant Takata Pharmaceutical, and Appellant
Pola Pharma is a stock company engaging in the business of sale, etc. of medicines,
respectively.
(2) Maxacalcitol
A. The appellee prepares and sells products named "Oxarol Ointment" and "Oxarol
Lotion," respectively, which are cures for keratoma and whose active ingredient is
maxacalcitol, an activated vitamin D3 derivative.
B. For many years, calcium metabolism-controlling activity has been known as aphysiological activity of activated vitamin D3. A broad range of new activities,
including growth-inhibiting activity and differentiation-inducing activity on cells, werediscovered, and activated vitamin D3 has become expected to serve as a cure fordyskeratosis. However, activated vitamin D3 has a problem of a side effect, that is, anincrease in the blood calcium level.
The appellee discovered that maxacalcitol, which is a substance that is made bymodifying the chemical structure of calcitriol, which is activated vitamin D3, has weak
blood calcium level increasing activity while it has growth-inhibiting activity anddifferentiation-inducing activity on cells. That is, the drawing below to the left indicatesvitamin D3 (inactive), and the drawing below in the middle indicates calcitriol wherein
the 1α- and 25-positions of vitamin D3 are hydroxylated and activated (1α,25-dihydroxy3vitamin D3). The appellee discovered that it is possible to obtain a substance, whose
growth-inhibiting activity is better than calcitriol by 10 to 100 times and whose blood
calcium and phosphorus level increasing activity (a side effect) is significantly weaker
than calcitriol, by replacing the methylene group at the 22-position of calcitriol with theoxygen atom (entire import of argument). This substance is maxacalcitol (the drawing
below to the right).

Vitamin D3

Calcitriol (1α,25-dihydroxyvitamin D3)

Maxacalcitol

C. On December 26, 1985 (priority claim: December 28, 1984 (priority date)), theappellee filed a patent application (Exhibit Ko 1) for 9,10-seco-5,7,10(19)-pregnatriene
derivative, which contained maxacalcitol that was a novel substance. The appellee
obtained the registration of establishment of a patent right therefor (Patent No.
1705002) in October 1992. The duration of said patent right expired on December 26,
2010 after going through the registration of extension of the duration.
The Corrected Invention is related to a process for the preparation of a compoundcontaining this maxacalcitol.
(3) Patent Right
The appellee jointly owns the following patent right (the "Patent Right") fifty-fiftywith the Trustees of Columbia University in the City of New York (hereinafter referred
to as "Columbia University").
A. Patent number: Patent No. 3310301
B. Title of the invention: Intermediates for the synthesis of vitamin D and steroid
derivatives and process for preparation thereof
C. Filing date: September 3, 1997
D. Application number: Patent Application No. 1998-512795

4

E. Priority date: September 3, 1996 (a priority claim based on US60/025,361;
hereinafter referred to as the "Priority Date")
F. Registration date: May 24, 2002
G. Extension of the duration: On March 31, 2010, the extension of the duration of the
Patent Right was registered with the following content under Article 67, paragraph (2)of the Patent Act (incidentally, the effect of the aforementioned registration of extension
does not become a problem in this case because the appellee seeks an injunction for theperiod until the last day of the duration before the registration of extension).
(A) Disposition which serves as a reason for the extension of the duration of the Patent
Right
Approval set forth in Article 14, paragraph (9) of the Pharmaceutical Affairs Act (theAct prior to the change of the title of the law by Act No. 84 of 2013) pertaining to a
medicine as provided for in said paragraph(B) Number to specify the disposition
Approval No. 21800AMX10386000(C) Article subject to the disposition
Maxacalcitol (generic name)(D) Usage specified in relation to the article subject to the disposition
Palmoplantar pustulosis(E) Period of the extension
Five years(4) Invention
The statement of Claim 13 in the scope of claims in the Description is as follows.
"[Claim 13]
A process for preparing a compound having the following structure:(in the formula, n is an integer from 1 to 5;
each of R1 and R2 independently is optionally substituted C1-C6 alkyl;
each of W and X is independently hydrogen or C1-C6 alkyl;
Y is O, S or NR3 where R3 is hydrogen, C1-C6 alkyl or a protective group; andZ is a CD ring structure of the formula:5

a steroid ring structure of the formula:or a vitamin D structure of the formula:wherein each of the structures of Z may optionally have one or more protected or
unprotected substituents and/or one or more protective groups, and wherein any ring of
the structure of Z may optionally have one or more unsaturated bonds);
which comprises:[a] the step of reacting a compound having the following structure:(in the formula, W, X, Y and Z are as defined above)in the presence of a base, with a compound having the following structure:6

or(in the formula, n, R1, and R2 are as defined above, and E is an eliminating group)
to produce an epoxide compound having the following structure:[b] the step of treating the epoxide compound with a reducing agent to produce thecompound; and[c] the step of recovering the compound so produced."(5) Request for a trial for patent invalidation and request for correction
On May 2, 2013, Cerbios-Pharma SA (hereinafter referred to as "Cerbios") filed arequest for a trial for patent invalidation (Invalidation Trial No. 2013-800080) in
relation to the Patent (patent pertaining to Claims 1 to 30) (Exhibit Ko 28).
The appellee and Columbia University submitted a written request for correction
dated September 25, 2013 (Exhibit Ko 15) to request the correction of the Description(the number of claims after the correction is 28; hereinafter, said correction is referred toas the "Correction," and the description after the Correction is referred to as the"Corrected Description"; incidentally, only the scope of claims in the Description wascorrected by the Correction) for the purpose of restriction of the scope of claims. On
July 25, 2014, the JPO rendered a decision to the effect that "The correction shall be
accepted as requested. The request for a trial in question shall be dismissed" (Exhibit Ko
28).
Cerbios instituted an action to seek the rescission of said JPO decision (2014(Gyo-Ke) 10263) with the Intellectual Property High Court. However, on December 24,

7

2015, said court rendered a judgment that dismissed Cerbios's claim, and said judgment
became final and binding (Exhibits Ko 33 and 34).
(6) Corrected Invention
A. The statement of Claim 13 after the Correction is as stated in [Claim 13] in the scopeof claims in the Corrected Description attached to the judgment in prior instance, andthe invention pertaining to said claim (Corrected Invention; hereinafter, in the Patent,
the patent pertaining to said claim is referred to as the "Patent Pertaining to theCorrected Invention") is segmented into the following constituent features (underlined
parts are corrected parts; Constituent Features [A-1] and [A-2] to [A-6] are collectively
referred to as "Constituent Feature [A]," and Constituent Features [B-1] to [B-3] arecollectively referred to as "Constituent Feature [B]").
[A-1] A process for preparing a compound having the following structure:[A-2] (in the formula, n is 1;[A-3] R1 and R2 are methyl;[A-4] each of W and X is independently hydrogen or methyl;[A-5] Y is O; and[A-6] Z isa steroid ring structure of the formula:or a vitamin D structure of the formula:8

wherein each of the structures of Z may optionally have one or more protected or
unprotected substituents and/or one or more protective groups, and wherein any ring of
the structure of Z may optionally have one or more unsaturated bonds);[E] which comprises:[B-1] [a] the step of reacting a compound having the following structure:(in the formula, W, X, Y and Z are as defined above)[B-2] in the presence of a base, with a compound having the following structure:or(in the formula, n, R1, and R2 are as defined above, and E is an eliminating group)[B-3] to produce an epoxide compound having the following structure:9[C] [b] the step of treating the epoxide compound with a reducing agent to produce thecompound; and[D] [c] the step of recovering the compound so produced."
B. The Correction is intended to limit "Z" of the objective substance and the starting
material of the Invention to those having a "steroid ring structure" or a "vitamin D
structure" and also to limit a side chain to be introduced to those having the following
structure (3-hydroxy-3-methylbutoxy group; hereinafter referred to as a "Maxacalcitol
Side Chain"). The Correction restricts the scope of claims (incidentally, among suchobjective substances, a substance in which "Z" has a "vitamin D structure" and which
has two hydroxy groups [OH] in "Z" as substituents is maxacalcitol).

The Appellant's Process does not fall under the part that was excluded from theInvention by the Correction (the parties do not dispute this point).
(7) Appellants' acts
A. Appellant DKSH imports Appellant's Product 1, which was prepared by Cerbios, a
Swiss drug manufacturer, by the Appellant's Process, as a business and sells it at least to
Defendant Takata Pharmaceutical and Defendant Pola Pharma.
B. On August 15, 2012, Appellant Iwaki Seiyaku, Appellant Takata Pharmaceutical,
and Appellant Pola Pharma obtained the approval of the Minister of Health, Labour andWelfare in relation to the preparation and sale of Appellants' Products 2(1) to (3),respectively. These products were listed in the National Health Insurance Drug Price
Standard on December 14 of the same year.
Any maxacalcitol that is contained in Appellants' Products 2 as an active
pharmaceutical ingredient (active ingredient) was prepared by the Appellant's Process.
C. The Appellant's Process is as stated in the Process List attached to this judgment, and10

it is in short a process for preparing maxacalcitol which comprises [i] the step ofreacting Starting Material A with Reagent B (1-bromo-3-methyl-2,3-epoxybutane; it isalso referred to as "4-bromo-2,3-epoxy-2-methylbutane"; hereinafter referred to as the"Reagent" in some cases) in the presence of a base to synthesize Intermediate C of an
epoxide compound (Step I), [ii] the step of opening the ring of the epoxy group bytreating Intermediate C with a reducing agent to obtain Substance D (trans form of
maxacalcitol) (Step II), [iii] the step of converting Substance D to a cis form andremoving protective groups to obtain maxacalcitol, which is the objective substance(Step III), and [iv] the step of recovering maxacalcitol (Step IV).
D. The Appellant's Process fulfills Constituent Features [A], [B-2], [D], and [E] of theCorrected Invention.
The Appellant's Process does not fulfill Constituent Feature [B-1] of the Corrected
Invention in that the carbon skeleton of Starting Material A in Step I is not a "cis-form
vitamin D structure" (cis (5Z) secosteroid structure) which "has one or more protected… substituents" and has two protected substituents among "Z" of Constituent Feature[A-6] cited in Constituent Feature [B-1] of the Corrected Invention" but is a trans-form
vitamin D structure (trans (5E) secosteroid structure), which is a geometric isomer ofsaid cis-form vitamin D structure.
(Vitamin D structure of Z in the Corrected (Carbon skeleton of Starting Material A
Invention)

for the Appellant's Process)(Z may have one or more protected
substituents.)
In addition, the Appellant's Process does not fulfill Constituent Features [B-3] and[C] of the Corrected Invention in that the carbon skeleton of Intermediate C in Steps I
and II is not a cis-form vitamin D structure but a trans-form vitamin D structure in thesame manner as the above.
Incidentally, the basic skeleton of vitamin D group includes three double bonds
connected from the upper two rings (triene; double bonds are indicated by double lines

11

in the following figures). In vitamin D group, there are two geometric isomers thatderive from this triene structure. A vitamin D having the left-hand triene sequence in thefollowing figures is called "cis form," and a vitamin D having the right-hand triene
sequence is called "trans form."

5-position

5-position

Cis form

Trans form

3. Issues
The issues of this case are [i] whether the Appellant's Process falls under thetechnical scope of the Corrected Invention as an equivalent thereto and [ii] whether the
Patent Pertaining to the Corrected Invention is recognized as one that should beinvalidated by a trial for patent invalidation (existence or absence of the grounds forinvalidation mentioned in (2)A. to C. below).
(1) Whether the Appellant's Process is equivalent to the Corrected Invention(2) Whether there are grounds for invalidation in relation to the Corrected Invention
A. Lack of an inventive step by citing Exhibit Otsu 14 Document as the primarily cited
document (Ground for Invalidation A)
B. Lack of an inventive step by citing Exhibit Ko 12 Document as the primarily cited
document (Ground for Invalidation B)
C. Lack of an inventive step by citing Exhibit Otsu 4 Document as the primarily cited
document (Ground for Invalidation C)
Incidentally, in prior instance, the appellants alleged Grounds for Invalidation 1, 2,
and 4 to 6 (Ground for Invalidation 3 is a vacant number) as briefly indicated in No. 2, 3.
in "Facts and reasons" in the judgment in prior instance. However, in this instance, theappellants backed off their allegations of Grounds for Invalidation 1, 5, and 6 as briefly
indicated in No. 2, 3. in "Facts and reasons" in the judgment in prior instance, andalleged the lack of an inventive step by citing Exhibit Ko 12 Document as the primarily
cited document (the aforementioned Ground for Invalidation B) as a new ground for12invalidation. Therefore, the grounds for invalidation to be examined in this instance are
only the aforementioned Grounds for Invalidation A to C.
No.3 Allegations of the parties
1. Regarding whether the Appellant's Process is equivalent to the Corrected Invention
The allegations of the parties concerning the fulfillment of the first to fifth
requirements of the doctrine of equivalents are supplemented as follows by theallegations of the parties in this instance, and are also as briefly indicated in No. 3, 1. to
5. in "Facts and reasons" in the judgment in prior instance. Therefore, the relevant partis cited (however, in the judgment in prior instance pertaining to the citation, the terms"plaintiff," "defendant," "Defendant's Process," and "Constituent Feature [A-6']" aredeemed to be replaced with "appellee," "appellant," "Appellant's Process," and"Constituent Feature [A-6]," respectively [hereinafter the same shall apply in the case ofcitation]; the phrase "hereinafter referred to as the 'Reagent'" in line 21 of page 16 of thejudgment in prior instance and "Exhibit Otsu 4-2" in line 14 of page 19 are revised tothe "Reagent" and "Publication of Japanese Translation of PCT International
Application No. 1992-504573 (hereinafter referred to as Exhibit Otsu 4 Document),"
respectively).
(Supplementary allegations of the parties in this instance)(1) Regarding the first requirement of the doctrine of equivalents(Appellants)
A.(A) In the case of using a starting material having a cis-form vitamin D structure, thestarting material and the intermediate are candy-like and unstable. Therefore, there are
difficulties in handling and using such starting material. In addition, as such starting
material is not crystal, it needs to be purified by column chromatography using silica,
which is an oxidation catalyst, as filler. Therefore, there is a loss at the time of
purification as vitamin D is easily degraded by oxidation.
On the other hand, in the Appellant's Process, all of Starting Material A (trans form),
Intermediate C (trans form) obtained by reaction with Reagent B, and Substance D(trans-form maxacalcitol) obtained by opening the ring of Intermediate C are crystal andhighly stable, and they can be extracted and preserved as crystal in the middle of asynthesis route. Moreover, as they can be purified by recrystallization, the number ofkinds of analogues and the amount thereof can be reduced.
In this manner, the Appellant's Process has a technical significance that theCorrected Invention does not have, as a manufacturing process, in that it increases thestability of steps and easiness of purification. On the other hand, it differs from theCorrected Invention in terms of the number of steps. That is, the Corrected Invention

13

comprises two steps while the Appellant's Process comprises three steps.
(B) Originally, processes using a starting material having a cis-form vitamin D structure,
those using a starting material having a trans-form vitamin D structure, and those using
a starting material having a steroid ring structure have been understood as different
general processes for the synthesis of vitamin D3 derivatives by persons ordinarily
skilled in the art.
In addition, the Corrected Description includes the following statement: "Some of
the compounds which are used as the starting compound in the aforementioned processaccording to the present invention are publicly known compounds. For example, … the9,10-seco-5,7,10(19)-pregnatriene-1α,3β,20β-triol optionally with the hydroxyl group
being protected described in … International Patent Publications WO/1990/09991(September 7, 1990) and WO/1990/09992 (September 7, 1990)." In the publications
corresponding to these two international patent publications (Exhibits Otsu 3-2 and 4-2),trans form and cis form are distinctively described. It is described in the latter
publication that an additional step is required for conversion from a trans form to a cisform and that cis-form maxacalcitol is prepared from a trans-form starting material. The
case of using a cis-form starting material and the case of using a trans-form starting
material are distinguished from each other.
In the end, the Corrected Invention using a cis-form starting material is established
as a separate process from a process using a trans-form starting material.
(C) In the technical field of processes for the preparation of a compound, reactivity
differs in some cases depending on a difference in the structure of a compound or aslight difference in the reaction conditions. All the steps before obtaining the objective
substance from the starting material are organically linked, and this organic linkage
itself is a technical idea for solving a problem. Therefore, a change in the constituent
elements or combination of the steps leads to a different technical idea.
As mentioned in (A) above, the Appellant's Process differs from the Corrected
Invention in terms of the starting material, the intermediate, and the necessity of a stepof isomerization from the intermediate. In addition, it also differs in terms of thestability of steps and easiness of purification.
The starting material just falls under an essential part in terms of where the starting
point of a series of steps to obtain the objective substance is placed. As mentioned in(B) above, processes using a starting material having a cis-form vitamin D structure andthose using a starting material having a trans-form vitamin D structure are understood as
separate processes. The intermediate also falls under an essential part in terms of where
the pass point in a series of steps to obtain the objective substance is placed. As

14mentioned in (A) above, a choice between stable steps and reduced number of steps
depends on whether the process goes through trans-form maxacalcitol. Therefore, theintermediate just falls under the essential part of a manufacturing process.
There is no other choice but to say that it is erroneous to extract part of amanufacturing process in disregard of such differences in the stating material and theintermediate, which are the important constituent elements of the manufacturing process,as well as differences in stability and the number of steps. The essence of the Corrected
Invention exists not in its part but in the entire manufacturing process, and theAppellant's Process, which differs from the Corrected Invention in the starting material
and the total number of steps, cannot be considered to be essentially identical with theCorrected Invention.
B.(A) In addition, a cis-form vitamin D structure and a trans-form vitamin D structure
differ in that the former has low oxidation resistance while the latter has high oxidation
resistance. The conventional manufacturing process described in Publication of
Unexamined Patent Application No. 1994-256300 (hereinafter referred to as "Exhibit
Otsu 46 Publication") wherein the starting material is an alcohol compound at the
20-position of a steroid ring structure is difficult to apply because it has the following
problem: In the case of using a starting material having a cis-form vitamin D structure,
the starting material has low oxidation resistance, and thus, protection of the triene
structure is indispensable for the selective introduction of an epoxy group into a side
chain; therefore, introduction of a side chain cannot be efficiently conducted. For the
purpose of solving said problem, in the Corrected Invention, a cis-form vitamin D
structure is chosen as the starting material, and the order of introduction of an etherbond and an epoxy group conformable to such structure is found. Consequently, theessence of the Corrected Invention exists in that it solved a problem (oxidation
resistance) that arises in the case of using a starting material having a cis-form vitamin
D structure while enjoying the advantage of the reduced number of steps by using such
starting material. The point that the starting material has a cis-form vitamin D structure
is an indispensable essential element.
In contrast to this, in the case of using a starting material having a trans-form
vitamin D structure, an isomerization step is by necessity required to obtain theobjective substance. Therefore, it is impossible to enjoy the advantage of the reduced
number of steps in the entire manufacturing process, which can be achieved in the caseof using a starting material having a cis-form vitamin D structure. On the other hand,unlike a cis-form vitamin D structure, a trans-form vitamin D structure has highoxidation resistance. Therefore, it is possible to efficiently introduce an epoxy group15

into a side chain by using a conventional oxidation process. Consequently, there is no
problem relating to oxidation resistance, and it is thus not necessary to use the principle
whereby the problem is solved. Next, a trans-form vitamin D structure has many
advantages, such as the capacity of stocking epoxy intermediate and recovery of target
compounds by recrystallization, as it is crystalline and excellent in stability.
Furthermore, in the case of using a vitamin D structure as the starting material, it isnecessary to introduce a hydroxyl group at the 1-position at any of the steps. In this case,
it is more favorable to adopt a trans-form vitamin D structure.
(B) The only effect stated in the Corrected Description is the reduction of the number ofsteps, and the effect of the Corrected Invention exists in the reduction of the number ofsteps compared to prior art. There has been no manufacturing process, as prior art,
whereby a Maxacalcitol Side Chain can be introduced in two steps in the case of using astarting material having a steroid ring structure or a cis-form vitamin D structure, likethe Corrected Invention. However, in the case of using a starting material having atrans-form vitamin D structure, a Maxacalcitol Side Chain can be introduced throughone step by a process described in Publication of Japanese Translation of PCT
International Application No. 1992-504573 (Exhibit Otsu 4 Document), which is
introduced as prior art in the Corrected Description. Therefore, it is impossible to allege
the effect of reducing the number of steps compared to prior art.
C. As mentioned above, the effect of the Corrected Invention as a manufacturing
process completely differs depending on whether the starting material has a cis-form
vitamin D structure or a trans-form vitamin D structure, and the Corrected Invention canbe established as separate inventions accordingly. In the latter case, the Corrected
Invention does not have the effect of reducing the number of steps compared to prior art.
Therefore, the Appellant's Process cannot be considered to be identical with theCorrected Invention in the essential part, and does not fulfill the first requirement of thedoctrine of equivalents.
(Appellee)A.(A) The issue of the essential part of an invention in the doctrine of equivalents is not
the question of whether there are differences between the subject product, etc. and thepatented invention but is the question of whether differences between them are related
to the essential part of the patented invention. Even if there are differences between
them, if those differences are not in the essential part of the patented invention and arein the matters which a person ordinarily skilled in the art can choose as appropriate, andthe subject product, etc. and the patented invention are identical with each other in theessential part, the first requirement of the doctrine of equivalents is fulfilled.

16

Differences in stability and easiness of purification between a cis form and a transform as alleged by the appellants are not related to the process for introducing a
Maxacalcitol Side Chain, which is the essential part of the Corrected Invention. Even if
the Corrected Invention is considered to be a different process depending on the starting
material, this does not serve as a reason for denying that the Corrected Invention and theAppellant's Process are substantially identical with each other.
(B) The reduction of the number of steps compared to prior art is not the only functionand effect of the Corrected Invention. As the Corrected Invention is a specific chemical
reaction for the introduction of a Maxacalcitol Side Chain, it should be compared to all
the other publicly known processes for the introduction of a Maxacalcitol Side Chain inorder to express its effect most accurately. The processes whereby a Maxacalcitol Side
Chain could be introduced prior to the filing of the application for the Patent were only
the following three: [i] the first process for the synthesis of maxacalcitol, which wasdeveloped by the appellee (Exhibit Ko 12; this process is very inefficient inconsideration of industrial production for such reasons as that it produces a large
amount of by-products and also requires sensitivity to safety in the context of use ofoxygen); [ii] the synthesis process called Michael process as of the time of the clinicaltest, which was developed by the appellee as an improved process of the said firstprocess (Figure 6 in Exhibit Otsu 14; this process is difficult to use for mass production
as it uses a large amount of cerium chloride, which needs to be treated as metallic
waste); and [iii] the process using prenyl bromide as the reagent, which was carried out
by the inventors of the Corrected Invention (this process cannot be used for industrial
production as it requires a mercury compound to selectively introduce a hydroxyl groupat the 25-position, which is the end of the side chain). None of these processes was
suited for industrial production. The Corrected Invention is the first process for the
introduction of a Maxacalcitol Side Chain which is industrially practicable, and its
effect exists in a difference in the process for the introduction of a Maxacalcitol Side
Chain from the aforementioned conventional processes for the introduction of a
Maxacalcitol Side Chain.
Therefore, the essential feature of the Corrected Invention exists in the novel
process for the introduction of a Maxacalcitol Side Chain, which made it possible tomass produce maxacalcitol for the first time, by way of the reaction between an alcoholcompound at the 20-position and the reagent of Constituent Feature [B-2], wherein the
double bond of prenyl bromide is oxidized into an epoxy substance in advance. The
Appellant's Process has this essential feature in common with the Corrected Invention.
B. As the side chain introduction process of the Corrected Invention does not include

17

oxidation reaction, difference in oxidation resistance between a cis form and a transform does not affect the introduction of a Maxacalcitol Side Chain of the Corrected
Invention. In addition, as the reaction of the Corrected Invention is carried out in asolvent, the fact that a trans-form vitamin D structure is crystalline and excellent instability has no relation in the process of the Corrected Invention. Furthermore, the factthat it is favorable to adopt a trans form in terms of the introduction of an hydroxyl
group at the 1-position is nothing more than the advantage of a trans form in relation tothe obtainment of the starting material because the starting material has a hydroxyl
group at the 1-position, irrespective of whether it is a cis form or a trans form.
Incidentally, there is no ground for the appellants' allegation that a Maxacalcitol Side
Chain could be introduced through one step by prior art in the case of using a starting
material having a trans-form vitamin D structure.
C. Therefore, the difference between the Corrected Invention and the Appellant's
Process is not the essential part of the Corrected Invention, and the Appellant's Processthus fulfills the first requirement of the doctrine of equivalents.
(2) Regarding the second requirement of the doctrine of equivalents(Appellants)
A. As the appellants' allegation in B. in (1) above, the effect of the Corrected Invention
exists in the reduction of the number of steps compared to prior art. In the case of aprocess wherein the starting material has a trans-form vitamin D structure, it has beenpossible to introduce a Maxacalcitol Side Chain through one step for some time now.
Therefore, it is impossible to allege the effect of reducing the number of steps compared
to prior art.
B. In addition, the efficiency of the effect of the Corrected Invention of reducing thenumber of steps should be decided based on the total number of steps in the
manufacturing process. Looking at the total number of steps in the manufacturing
process, the number of steps increases in the Appellant's Process because of thenecessity of a step of isomerization from a trans form to a cis form, and three steps aresubstantially required to obtain the objective compound. Therefore, the Appellant's
Process does not have the same function and effect as the Corrected Invention, and it
cannot be considered to be a "replacement" at all.
C. Other than these, as the appellants' allegation in A.(A) in (1) above, the Appellant's
Process has a technical significance that the Corrected Invention does not have, and theactual yield is not the same as that in the case of using a cis-form starting material.
Therefore, the Appellant's Process is considered to be different processes in the case ofusing a cis-form starting material and in the case of using a trans-form starting material.

18

Consequently, the Appellant's Process differs from the Corrected Invention, and it is notconsidered to be possible to "replace" them.
D. Therefore, the Appellant's Process does not fulfill the second requirement of thedoctrine of equivalents.
(Appellee)
The fact that the number of steps was reduced compared to prior art cannot be
considered to be the only function and effect of the Corrected Invention, as theappellee's allegation in A.(B) in (1) above.
Even if the reduction of the number of steps is the function and effect of theCorrected Invention, said effect is obtained by using the Reagent and omitting theoxidation step after reaction with a reagent that was carried out in prior art.
Consequently, even if the starting material is replaced with one having a trans-form
vitamin D structure, the same function and effect as those of the Corrected Invention
can be produced.
(3) Regarding the third requirement of the doctrine of equivalents(Appellants)
A. As the appellants' allegation in A.(B) in (1) above, processes using a starting material
having a cis-form vitamin D structure, those using a starting material having atrans-form vitamin D structure, and those using a starting material having a steroid ring
structure are understood as different processes for the synthesis of vitamin D derivatives.
A person ordinarily skilled in the art cannot easily conceive of the fact that the same
effect of reducing the number of steps, which is expected to be achieved by theCorrected Invention, can also be achieved even if the starting material having a cis-form
vitamin D structure is changed to a starting material having a trans-form vitamin D
structure.
B. The Corrected Description does not contain any working example wherein thestarting material has a cis-form vitamin D structure. Therefore, whether or not reaction
proceeds in the case of using a starting material having a cis-form vitamin D structure isoriginally unclear for a person ordinarily skilled in the art who sees the Corrected
Description. Furthermore, it is totally unclear whether or not reaction proceeds in thecase of the process using a starting material having a trans-form vitamin D structure,
which is recognized as a process that is different from the process using a starting
material having a cis-form vitamin D structure, and this is not considered to be as clear
as if stated in the scope of claims. Therefore, it cannot be said that a person ordinarily
skilled in the art can easily replace a cis-form with a trans-form.
C. Consequently, the Appellant's Process also does not fulfill the third requirement of

19

the doctrine of equivalents.
(Appellee)
A reaction experiment using a starting material having a cis-form vitamin D
structure under the experiment conditions of the working example of the Corrected
Description immediately reveals that the reaction can be carried out. In the field ofvitamin D, the mutual converse relationship between a trans form and a cis form iswell-known among persons ordinarily skilled in the art. Therefore, an experiment
immediately reveals that the reaction can also be carried out in the case of using astarting material having a trans-form vitamin D structure.
Therefore, the Appellant's Process fulfills the third requirement of the doctrine ofequivalents.
(4) Regarding the fifth requirement of the doctrine of equivalents(Appellants)
A. Regarding inventions in the chemical field for which the subject of the invention is
objectively and easily defined under certain rules by using chemical formulas andnames of compounds, there naturally arises the third-party trust that a right will never be
expanded from its clear scope based on the objective and clear statements in the scopeof claims that are indicated by chemical formulas. It is extremely difficult for a third
party to foresee expansion of the scope of a right beyond the statements in the scope ofclaims. The level of the third-party trust in the statements in the scope of claims totallydiffers between inventions in the chemical field for which the clear provision of thescope of rights is required and inventions in the fields for which functional expressions
are permitted. It is indicated in the judgment of the Supreme Court of December 14,
1972 (Phenothiazine Derivative Manufacturing Process case) that the third-party trust in
the statements in the scope of claims should be protected in relation to chemical
inventions. In the judgment of the Supreme Court of June 5, 2015 (Product-by-Process
Claim case), the court also indicates the necessity of weighing the applicant's burden ofclearly stating the scope of the exclusive right which he/she alleges and the third party's
burden of predicting the scope to which the right extends based on the statements in thescope of claims, in relation to the interpretation of claims in the field of medicine likethis case.
For the Corrected Invention for which the scope of claims is stated by chemical
formulas, it is safe to say that the applicant bears little burden to include a trans-form
starting material in the scope of claims at the time of filing the application. On the other
hand, there naturally arises the third-party trust that the right will never be expandedfrom the scope of claims specified by objective and clear expressions, as mentioned

20

above. In weighing the applicant's burden and the third-party trust, the third-party trust
should be protected more in light of the principle of "fairness," which is the principle ofequivalents.
In the first place, in the judgment of the Third Petty Bench of the Supreme Court of
February 24, 1998, Minshu, Vol. 52, No. 1, at 113 (hereinafter referred to as the"Supreme Court Judgment on the "Ball spline bearing" Case"), the court first indicatesthat it is a principle to comply with the provisions of Article 70, paragraph (1) of the
Patent Act, which is a statute law. The court then indicates that the doctrine ofequivalents is applicable only within the scope that does not inhibit the development ofindustry, which is the purpose of the Patent Act. Thereby, the court only approves thedoctrine of equivalents on the premise of the existence of a reason for protecting thepatentee even in contradiction to the principle of the Patent Act. Approving theestablishment of equivalence in this case leads to approving an argument that ignores
the aforementioned principle of the Patent Act to the effect that the applicant may
prepare claims on the premise of the expansion of a right by application of the doctrineof equivalents, which will cause extensive damage to third parties who believe in the
public notice function of the patent system.
B. In addition, in this case, the reason for the applicant to describe the starting material
having a cis-form vitamin D structure alone is not a difficulty or a mistake at the time offiling the application, according to the circumstances mentioned below. There is no
circumstance where the applicant forgot to state a trans-form vitamin D structure whendefining the starting material. In stating the scope of claims, the applicant decided thestarting material, being clearly and objectively conscious of not including a trans-form
vitamin D structure in the scope of claims. The applicant thus intentionally chose toactively exclude a trans-form vitamin D structure.
(A) It is a well-known matter that there are two kinds of geometric isomers, cis form
and trans form, as the basic skeletons of vitamin D and that there are only these twokinds of basic skeletons in the natural world. In addition, as of the Priority Date, a routefor the synthesis of a vitamin D derivative using a starting material having a trans-form
vitamin D structure was widely known among persons ordinarily skilled in the art. The
inventors of the Patent who study vitamin D derivatives should have known these facts
very well. Therefore, the applicant was never erroneously ignorant of the existence of asynthesis route using a starting material having a trans-form vitamin D structure as of
the Priority Date.
Moreover, as the appellants' allegation in A.(B) in (1) above, processes using astarting material having a trans-form vitamin D structure and those using a starting21

material having a cis-form vitamin D structure were understood as different processes inrelation to the synthesis of vitamin D derivatives.
(B) In Claim 13 in the scope of claims in the Corrected Description, a chemical bond is
described by a wavy line, "〰H," in the structural formula of Constituent Feature [B-3]of the Corrected Invention, and it is thereby clearly specified that the steric structure at
the root of H includes both R-stereoisomer and S-stereoisomer. However, the geometricisomer of a vitamin D structure is described as being limited to a cis form. The applicant
can immediately understand that a trans form is not included in the scope of claims anda third party also understand as such if the applicant describes only a cis form in thescope of claims in relation to geometric isomer while clearly specifying that both of said
stereoisomers are included. Therefore, in the Corrected Description, the applicant
clearly and objectively states that a trans form is not included in the scope of claims.
(C) Moreover, as the appellants' allegation in A.(B) in (1) above, the detailed
explanation of the invention (in lines 32 to 48 in column 41) in the Corrected
Description describes two international publications describing a starting material
having a trans-form vitamin D structure, in addition to a patent gazette describing astarting material having a cis-form vitamin D structure. Despite that, it is stated in the
Corrected Description (in lines 10 to 12 in column 37) that "each of the CD ring
structure, steroid structure, and vitamin D structure for the present invention particularlymeans a structure as described below … (omitted)." The chemical structural formula ofa cis-form vitamin D structure is then chosen and described. As a result of this choice, a
cis-form vitamin D structure alone is stated in the scope of claims. In this manner, thestarting material is "particularly" limited to a cis form out of the two kinds of theexisting basic skeletons. Therefore, in the Corrected Description, the applicant clearly
and objectively states that a trans form is not included in the scope of claims.
Consequently, a trans-form vitamin D structure is intentionally excluded from the scopeof claims.
(D) Furthermore, the following figures are stated in the detailed explanation of theinvention (line 1 and thereafter in the right-hand column on page 20) in the Corrected
Description as examples of vitamin D structures protected by addition of SO2.

22

The left and right figures indicate the same compound, and it is sufficient to draw
the left figure to indicate an "example of vitamin D structures protected (by addition of
SO2)." Despite that, the aforementioned two structural formulas are presented in the
Corrected Description, which can only be interpreted as meaning that each of thesestructural formulas expresses a structural formula immediately after addition of SO2 to a
cis-form starting material (structural formula on the left side) and a structural formula
immediately after addition of SO2 to a trans-form starting material (structural formulaon the right side), respectively, as indicated in the following figures.

Cis form
Trans form

In addition, it is common general technical knowledge as of the Priority Date that if
a vitamin D derivative to which SO2 is added as a protective group is used as a starting
material, it necessarily becomes a trans form in alkylation reaction (Exhibit Otsu 1).
Despite the existence of such a statement that is based on the assumption of atrans-form starting material in the "detailed explanation of the invention" section in the
Corrected Description, the starting material is limited to a cis-form starting material in
the scope of claims. Therefore, an intentional limitation is also clear in this regard.
(E) Although the Corrected Description includes only working examples using a starting23

material having a steroid ring structure, the Corrected Invention is enlarged to include
the cases where the partial structure corresponding to "Z" is a cis-form vitamin D
structure. The applicant also knew that if the applicant specifies the starting material asa cis form when adding a vitamin D structure to the scope of right as enlargement fromworking examples, this leads to setting the limits of enlargement and such statement
defines the scope to which the right can be claimed against third parties. In addition, if a
specifically stated invention has already been generalized and a third party sees thedescription wherein the invention is stated in the scope of claims as the scope of
exclusive right alleged by the applicant him/herself, the third party naturally recognizes
as follows: The scope to which the right extends was determined after consideration of
the partial structure corresponding to "Z", and at the same time, a vitamin D structurethat was not stated in the scope of claims was excluded from the scope to which theright extends.
(F) As it was not required to state a specific working example for each starting material
in the examination practice at the time of the filing of the patent application in question,
the starting material the applicant chose was totally voluntary. The applicant could
choose any of a cis-form vitamin D structure, a trans-form vitamin D structure, a steroid
ring structure, and a CD ring, etc. as the partial structure corresponding to "Z" of thestarting material, and there was no difficulty in including a trans form.
(G) It can be understood that the applicant limited starting materials having a vitamin D
structure to those having a cis-form vitamin D structure, in consideration of theinvolvement of an inventive step of the invention. That is, as the appellants' allegation in(2) above, the only function and effect stated in relation to the Corrected Invention in
the Corrected Description is "reduction of the number of steps," but said function andeffect cannot be alleged in the case of using a trans-form starting material because anadditional step of converting a trans form to a cis form is required. Moreover, in thecase of using a starting material having a trans-form vitamin D structure, the effect of
reducing the number of steps compared to prior art cannot be achieved because there are
publicly known arts (Exhibits Otsu 4-2 and 50) whereby a side chain is introduced
through one step. Therefore, the applicant limited the starting material to cis-form
starting materials because it was highly likely to be unable to receive an examiner's
decision to grant a patent based on the allegation of the effect of reducing the number ofsteps if it included a starting material having a trans-form vitamin D structure in thesubject of the invention.
(H) As mentioned above, in the Corrected Invention, there are the "special
circumstances, such as the fact that the subject item falls under what is intentionally24excluded from the scope of claims," as mentioned in the Supreme Court Judgment on
the "Ball spline bearing" Case, in relation to a trans-form vitamin D structure, but there
is no circumstance where the patentee should be specially protected, which is indicatedin said judgment as a ground for the application of the doctrine of equivalents,
specifically, the fact that "it is extremely difficult to foresee all kinds of infringements… and state the scope of claims in the description." Then, the Corrected Description
does not disclose any invention using a trans-form starting material, and there isabsolutely no circumstance where it is against social justice unless the right is to be
expanded to include trans-form starting materials. On the other hand, a third party whosees the Corrected Description can only understand that the right of the Corrected
Invention does not extend to a manufacturing process using a starting material having atrans-form vitamin D structure.
C. In addition to the above, when the appellants adjusted earlier and later patents in
preparation for commercialization of the preparations, the appellee sent a document toAppellant DKSH, and thereby alleged not only that the Appellant's Process constitutes
infringement under the doctrine of equivalents in relation to a cis-form vitamin D
structure but also that the Appellant's Process constitutes literal infringement in relation
to a CD ring structure on the premise that a CD ring structure having an optional
substituent falls under those that form a trans-form vitamin D structure. In the Corrected
Description, a trans-form substituent-bonded vitamin D structure is not excluded inrelation to a CD ring structure, but only a cis-form vitamin D structure is stated in thescope of claims. Taking this fact into account, it is further clear that a trans form isintentionally excluded from the scope of claims in the case of a vitamin D structure. The
aforementioned appellee's document is intended to have the appellants reconfirm thecontent stated in the Corrected Description to the effect that the starting material islimited to a cis form in the case of using a starting material having a vitamin D structure.
This is an indication made by the patentee before the appellants started preparing andselling their preparations, and it should be considered to be an intentional limitation.
Moreover, the appellee only alleged equivalence in this lawsuit, and subsequently
deleted a CD ring from the options for "Z" by the Correction. Regarding the statements
concerning different constituent features, i.e. literal infringement in the case of a CDring and infringement under the doctrine of equivalents in the case of a cis-form vitamin
D structure, literal infringement can be alleged in relation to only one (CD ring) of them.
This fact indicates that a trans-form vitamin D structure is excluded from the statementsof the constituent features in relation to the other one (cis-form vitamin D structure).
Accepting the allegation of infringement under the doctrine of equivalents in place of25

the allegation of literal infringement in such a case goes against the principle of fairness
that underlies the doctrine of equivalents, i.e. protection of third parties.
D. Therefore, the Appellant's Process does not fulfill the fifth requirement.
(Appellee)
A. Whether or not the scope of claims is clearly stated has no relationship to thenecessity of applying the doctrine of equivalents or the principle of the doctrine ofequivalents. An invention is required to be clearly stated in the scope of claims, and it ispossible only in the case of an invention thus clearly defined to make an evaluation as towhether the relevant product is equivalent to the invention.
As long as the doctrine of equivalents is acknowledged by the Supreme Court
Judgment on the "Ball spline bearing" Case, an applicant can file a patent application on
the premise of said doctrine. In addition, a third party is required to evaluate a patent on
the premise of said doctrine. Therefore, a choice of a certain literal structure in thescope of claims does not necessarily become an indication of an intention to give up
alleging the right for structures other than the literal structure. The same applies even if"structures other than the literal structure" are widely known.
B. The appellants allege that the applicant should state all equivalent arts, which can beeasily known as of the filing date, in the description in a manner that they are includedin the scope of claims and that if the applicant fails to do so, he/she is not permitted toallege the applicability of the doctrine of equivalents. However, such obligation is notprovided for in any part of the Patent Act, and there is no ground therefor in the current
patent practice where the doctrine of equivalents has already been established.
According to the appellants' allegation, if the applicant makes an invention of a "cisform," he/she must also study an invention of a "trans form" for filing a patentapplication. Furthermore, the applicant also needs consideration at the time of filing anapplication so as to prevent the occurrence of other "intentional exclusion." The morematters to be considered to avoid "intentional exclusion," the longer study time isrequired. Therefore, more time, labor, and costs are required for filing a patentapplication. On the other hand, an infringer will be able to seek an equivalent to an
invention without worrying about infringement under the doctrine of equivalents byconsidering another person's patent and deeming that the doctrine of equivalents does
not extend to an equivalent unless the equivalent is stated in the scope of claims. Thissituation is unjustifiable.
(A) The appellants allege that if the applicant states "cis form" in the scope of claims
when only two kinds, cis form and trans form, exist, it means a "particular" limitation to
cis form. However, there is no reason for understanding that the statement of one of the26

two kinds is an active indication of the intention to "particularly" limit the invention.
(B) The following is stated in column 37 in the Corrected Description, as pointed out by
the appellants, in the course of the explanation of the structural formulas of the starting
material of the Corrected Invention: "Each of the CD ring structure, steroid ring
structure, and vitamin D structure for the present invention particularly means astructure as described below." The three kinds of structural formulas of Z, which arestated in the scope of claims, are thus only stated. On the other hand, documents arecited in column 41 in the Corrected Description in relation to part of the starting
materials of the Corrected Invention that falls under the category of publicly known
compounds.
The appellants purposefully link these separate statements and thereby allege thatthe patent applicant intentionally excluded a trans-form vitamin D structure from thetechnical scope of the invention at the time of filing of the application. This allegation isexcessively arbitrary.
(C) The appellants allege that the limitation was made intentionally based on theexistence of statements concerning vitamin D structures protected by addition of SO2 in
the Corrected Description.
A protective group for SO2 is to protect a vitamin D structure from oxidation
reaction. However, the reaction of the Corrected Invention does not include any reactionthat possesses oxidizing properties. Therefore, said protective group is not a protective
group used in the reaction of the Corrected Invention but is an example of protective
groups used for vitamin D structures in general. The two figures of protective groups
stated in the Corrected Description have the same structure, and it is thus sufficient tostate one of these figures. However, both of these figures are stated. Therefore, theappellants' allegation that these figures indicate the applicant's intentional exclusion of atrans form is hard to understand.
(D) It is general in the patent practice that the technical scope of an invention stated in
the scope of claims is broader than specific embodiments stated in working examples,and even in such cases, it is not said that the scope of claims is "enlarged" from theworking examples. The appellants' allegation as if there were the "first-phaseenlargement" between the working examples and the scope of claims and the finding ofequivalence were the "second-phase enlargement" is not based on the correctunderstanding of the Patent Act.
C. The appellants make allegations based on the statements in the document which theappellee sent to the appellants before the filing of this action. However, in said
document, the appellee alleges that a trans-form vitamin D structure is equivalent to the27claims of a cis-form vitamin D structure, as well as a literal infringement of the claimsof a CD ring structure. Therefore, the allegation that such act falls under an intentional
exclusion is not understandable. Moreover, said document is nothing more than awritten counterargument of a lawyer against Cerbios's opinion. An expression of an
opinion made in such discussions does not fall under the special circumstances in thefifth requirement of the doctrine of equivalents.
D. The appellants allege that the acknowledgement of equivalence in this case goesagainst the ideas of fairness. However, this case is a case where protection under thedoctrine of equivalents should be granted based on the principle of fairness. The
appellee invented maxacalcitol in 1985 and conducted its clinical tests withconsiderable investment, and thereby developed a new business for medicine. However,as in the appellee's allegation in A.(B) in (1) above, conventional manufacturing
processes could not realize mass production or could only supply a small amount as an
expensive medicine even if the clinical tests were successful. The Corrected Invention,
which was discovered after a period of about 10 years, made it possible to supply
maxacalcitol to society as a medicine at a sufficiently reasonable price. The appellants
entered the market as generic medicine manufacturers in December of 2012 after theduration of the substance patent expired and the extended duration of the invention of
the use of maxacalcitol for the treatment of psoriasis expired in September 2012. This
market entry was possible because Cerbios supplied the active pharmaceuticalingredient of maxacalcitol at a price affordable for the appellants. Cerbios did notuniquely develop the Appellant's Process but came to know the Corrected Invention
from the technical information of the appellee and supplied the appellants with theactive pharmaceutical ingredient of maxacalcitol that it prepared by the Appellant's
Process on the assumption that it is possible to avoid infringement of the Patent bychanging cis form to trans form. Cerbios obtained the most important information, i.e.
the use of the Reagent, from the technical information of the appellee. This fact isobvious from the fact that Cerbios did not submit a document that corresponds to apaper titled "Reactions of 1-halo-3-methyl-2,3-epoxybutane with alcohols" wherein the
Reagent was stated (placed in a book titled "CHEMISTRY OF HETEROCYCLICCOMPOUNDS" that was distributed in 1982; hereinafter referred to as "Exhibit Otsu 9
Document") in a request for a trial for patent invalidation (Invalidation Trial No.
2013-800080), which Cerbios filed in relation to the Patent.
If it is possible, in this case, to avoid infringement of the Patent Pertaining to theCorrected Invention concerning an efficient industrial production process formaxacalcitol, which the researchers of the appellee had discovered through efforts over28

10 years, only by changing cis form to trans form, the infringers can enjoy the effect of
the efficient production achieved by the Corrected Invention and enter the market with
inexpensive generic medicines. This is not reasonable in light of the purpose of Article 1of the Patent Act.
E. Therefore, the Appellant's Process fulfills the fifth requirement.
2. Regarding whether there are grounds for invalidation in relation to the Corrected
Invention(1) Regarding the lack of an inventive step by citing Exhibit Otsu 14 Document as theprimarily cited document (Ground for Invalidation A)(Appellants)
A. Figure 9 in a paper written by Noboru Kubodera, which is titled "Active Vitamin D
Analogs - Important and Various Roles by Medicinal Chemists during the Course ofDevelopment of Promising Candidates as Useful Medicines" (Journal of Synthetic
Organic Chemistry, Japan, Vol. 54, No. 2; Exhibit Otsu 14; hereinafter referred to as"Exhibit Otsu 14 Document") describes a process for the synthesis of AnticipatedMetabolites of Maxacalcitol 12 and 13, which comprises the step of reacting the samestarting
material
as
that
of
the
Corrected
Inventionwith
4-bromo-2-methyl-tetrahydropyranyloxy-2-butene to produce a steroid compound
having a prenyl group, the step of subsequently producing Epoxide Compounds 18 and
19 by using the Katsuki-Sharpless reaction, and the step of light illumination andthermal isomerization by using DIBAH (diisobutylaluminum hydride) thereon(hereinafter referred to as "Exhibit Otsu 14 Invention").
The Corrected Invention and Exhibit Otsu 14 Invention differ in the following
points but are identical with each other in all the other points.
(Difference 1) Regarding a side chain, which is the objective substance, the side chainof the Corrected Invention is a Maxacalcitol Side Chain whose group at the end is amethyl group, while the side chain of Exhibit Otsu 14 Invention is one whose group at
the end is a hydroxymethyl group and is not a Maxacalcitol Side Chain.
(Difference 2) In the Corrected Invention, the reagent used for alkylation reaction is"4-bromo-2,3-epoxy-2-methylbutane" (the Reagent). On the other hand, in Exhibit Otsu
14 Invention, it is "4-bromo-2-methyl-tetrahydropyranyloxy-2-butene."(Difference 3) In the Corrected Invention, an epoxide compound having the following
structure is obtained by reacting the starting material, in the presence of a base, with theReagent:29n=1, R1, and R2 = methyl.
On the other hand, in Exhibit Otsu 14 Invention, a compound having the following
structure is produced by reacting the starting material with a reagent that differs fromthe Reagent:and then, epoxide compounds having the following structures are produced by using the
Katsuki-Sharpless reaction:

Compound 18

Compound 19

However, Difference 3 is a difference that naturally arises from Difference 2, and it
is not separate from and independent of Difference 2. Therefore, the only substantial
difference is Difference 2.
B. The aforementioned differences can be easily overcome as follows.
(A) Exhibit Otsu 14 Document is a document that considers a process for the synthesisof maxacalcitol as a whole, and it clearly specifies that a process for the industriallyefficient preparation of maxacalcitol is a technical problem.

30

(B) In addition, as indicated in Figure 1 below, Figure 9 in Exhibit Otsu 14 Document
describes a reaction of opening the ring of an epoxy group by reduction from an epoxide
compound, and also describes that the anticipated metabolite of maxacalcitol was
obtained in a good yield.
(Figure 1)

Reduction (ring-opening reaction)(Epoxide compound)(Anticipated metabolite)

The side chain of this anticipated metabolite was synthetized on the assumption of
the possibility that one of the methyl groups at the end of a Maxacalcitol Side Chain
will change to a hydroxymethyl group "on the assumption of the part that is easily
subject to metabolism in view of the structure" of maxacalcitol. It differs from a
Maxacalcitol Side Chain only in that one of the methyl groups at the end (CH3; theblue-colored part in Figure 1 above) is a hydroxymethyl group (CH2-OH; thered-colored part in Figure 1 above).
(C) In the study of organic synthesis, it is normal to obtain ideas from a process for thesynthesis of a compound having a similar structure. When seeing the statements in
Figure 9 in Exhibit Otsu 14 Document, a person ordinarily skilled in the art, who
intends to obtain the process for the efficient preparation of maxacalcitol described in
Exhibit Otsu 14 Document as a solution for the problem, can be motivated to apply thesynthesis process of Exhibit Otsu 14 Invention to the synthesis of maxacalcitol andchange the hydroxymethyl group in the epoxide compound to a methyl group by
focusing attention on the fact that the structures of the side chain of a vitamin D
derivative, which is the anticipated metabolite of Exhibit Otsu 14 Invention, and its
precursor, i.e. steroid compound, and the structure of a Maxacalcitol Side Chain arevery similar to each other as mentioned above.
In the ring-opening reaction indicated in Figure 1 above, the hydroxymethyl groupand methyl group at the end of the epoxide compound are preserved in the anticipatedmetabolite as they are. Therefore, a person ordinarily skilled in the art can easily
understand and conceive of the fact that even if the hydroxymethyl group in the epoxide
compound of Exhibit Otsu 14 Invention is replaced with a methyl group, both of the31methyl groups are preserved as indicated in Figure 2 below, and maxacalcitol can besynthesized by the ring-opening reaction of the epoxy group.
(Figure 2)

Epoxide compound

Steroid compound having the sameside chain as that of maxacalcitol

The fact that the hydroxymethyl group and the methyl group are preserved as they
are even after the opening of the ring of the epoxy group is consistent with the common
general technical knowledge of persons ordinarily skilled in the art (Exhibit Otsu 10).
Moreover, a process for forming a side chain wherein two methyl groups are bonded
at the end in the same manner as maxacalcitol by opening the ring of the epoxy group of
the epoxide compound having a steroid ring structure with a reducing agent had been
known by persons ordinarily skilled in the art prior to the Priority Date, as indicated in
Figure 3 below (Exhibit Otsu 19; however, the side chain indicated in Figure 3 differsfrom a Maxacalcitol Side Chain in that the atom at the 22-position is not an oxygen
atom but a carbon atom).
(Figure 3)

The inventors of the Corrected Invention themselves conceived of maxacalcitol byreplacing the carbon atom at the 22-position of a calcitriol side chain with an oxygen
atom (Exhibit Otsu 14). However, it is described in International Publication No.
1993/21204 (Exhibit Otsu 19; hereinafter referred to as "Exhibit Otsu 19 Document")
that an epoxide compound is used when forming the same side chain as said calcitriol
side chain. A person ordinarily skilled in the art can immediately understand that theprocess for forming a Maxacalcitol Side Chain described in Figure 9 in Exhibit Otsu 14
Document is very similar to the process for forming a side chain of Exhibit Otsu 1932

Document. A person ordinarily skilled in the art who has technical knowledge similar tothat which is described in Exhibit Otsu 19 Document has no difficulty in conceiving of
the synthesis of a maxacalcitol precursor (epoxide compound) from the epoxide
compound indicated in Figure 9 in Exhibit Otsu 14 Document.
Therefore, based on Figure 9 in Exhibit Otsu 14 Document, a person ordinarily
skilled in the art who recognizes the problem mentioned in (A) above can easily
conceive of using and is motivated to use an epoxide compound in which thehydromethyl group of the epoxide compound indicated in Figure 9 is replaced with amethyl group as the precursor of maxacalcitol for the purpose of synthesizing
maxacalcitol.
(D) Then, as mentioned below, it is easy to conceive of the alcohol compound at the
20-position of the steroid ring structure as the reagent and starting material of theCorrected Invention based on the epoxide compound indicated in Figure 2 above.
a. In considering the routes for the synthesis of known substances, "retrosynthesis" iscommon practice used by researchers in the field of organic synthesis (Exhibits Otsu 37
and 38). In retrosynthesis, researchers consider synthesis processes by starting from theobjective substance and retrograding required reactions. As of the Priority Date,retrosynthesis was a synthesis process which any person engaging in synthetic organic
chemistry has necessarily learned. It is natural for a person ordinarily skilled in the art touse retrosynthesis to solve the problem of efficiently producing a known substance,
maxacalcitol.
Retrosynthesis is applied to synthesize an epoxide compound that serves as aprecursor for the synthesis of maxacalcitol as efficiently as possible, and the matter thatis first considered is whether it is possible to synthesize such epoxide compound by
one-step reaction.
Looking at the epoxide compound indicated in Figure 2 above, it can be cut between
the oxygen atom of the ether bond and the carbon atom on its right side, as indicated in
Figure 4 below, and such cut is also reasonable from the perspective of organic
synthesis (Exhibit Otsu 39A Written Opinion).
(Figure 4)
Cutting into the starting material and the reagent by retrosynthesis analysis

33

Raw
material
EpoxidecompoundCutting part

Reagent

In the case of cutting as indicated above, the oxygen atom in the ether bond part iselectronically negatively charged. Therefore, a hydrogen atom that has low
electronegativity is added to cancel the negative charge. On the other hand, the carbon
atom, which is in the other part of the cutting, is electronically positively charged.
Therefore, Br or another halogen atom that has high electronegativity is added to cancel
the positive charge. This is common general technical knowledge. In fact, therelationship between the starting material and the reagent is also the same in Exhibit
Otsu 14 Invention, and a substance obtained by making the 22-position of the steroid
ring structure after this cutting be a hydroxyl group is the very starting material of
Exhibit Otsu 14 Invention.
b. Cutting at the aforementioned part is also consistent with the common generaltechnical knowledge of persons ordinarily skilled in the art. That is, a method ofalkylating the hydroxyl group at the 22-position of the starting material with alkyl
bromide is art which was well-known and common among persons ordinarily skilled in
the art as of the Priority Date (Exhibit Ko 1). In addition, it was also well-known as of
the Priority Date that a glycidyl ether compound can be synthesized by reacting acompound having an epoxy group, such as epibromohydrin, with alcohol whenalkylating a certain compound (Exhibits Otsu 6 to 8 and 29 to 31; Exhibit Otsu 31 inrelation to secondary alcohol that is bonded to a sterically complex three-membered ringskeleton; Exhibits Otsu 41 and 42 in relation to sterically complex steroid alcohol).
c. Based on the above, a person ordinarily skilled in the art who considers an efficientmanufacturing process for maxacalcitol can conceive, through application ofretrosynthesis, of applying the Reagent (compound indicated at the bottom right of
Figure 4 above; its structure is the same as that of the epoxy reagent of Corrected
Invention 1) which is obtained by first cutting an epoxide compound at the part
indicated in said figure and then adding Br on the side of the carbon atom to the starting
material of Exhibit Otsu 14 Invention (compound indicated at the top right of Figure 4;
the carbon skeleton of the starting material of the Corrected Invention is the same as34

that of a steroid ring structure; hereinafter referred to as the "Steroid Starting Material")
which is obtained by adding a hydrogen atom on the side of the oxygen atom.
In addition, in Exhibit Otsu 14 Invention, two steps, specifically, introduction ofprenyl and the Katsuki-Sharpless reaction, are required to introduce an epoxy group intoa side chain. However, a person ordinarily skilled in the art can easily understand that it
is possible to reduce the number of steps because an epoxy group can be introduced intoa side chain through one step by using the Reagent.
d. A person ordinarily skilled in the art who has conceived of the Reagent as above candiscover Exhibit Otsu 9 Document, in which the Reagent is described, as a result of
document search.
Exhibit Otsu 9 Document reports that the Reagent reacts with 10 kinds of alcoholsthat have different structures. Said document describes that among these alcohols,
isopropanol reacts with the Reagent in a good yield of about 50% despite the conditions
not being optimized.
The reaction between isopropanol and the Reagent is SN2 reaction. The issues thatarise in relation to the predictability of the obtainment of the objective product by SN2reaction are similarity in the structure of the functional group, which becomes thereaction site, and, for alcohols, similarity in the environment in the immediate vicinityof the reaction point, such as what grade of alcohol is the structure of the reaction point.
The molecular weight of the entire compound provided for reaction and the molecular
structure of the sites that are distant from the reaction site and are not related to reaction
do not become issues (Exhibit Otsu 39A Written Opinion and Exhibit Otsu 64).
Then, isopropanol is the secondary alcohol like the starting material of the Corrected
Invention, and isopropanol and the starting material of the Corrected Invention are very
similar to each other in the partial structure of the reaction site (the parts circled in bluein Figure 5 below). Therefore, a person ordinarily skilled in the art can understand thatSN2 reaction between the starting material of the Corrected Invention and the Reagent
also proceeds well.
(Figure 5)(Isopropanol)(Starting material of the Corrected Invention)

35

Looking at a molecule model, which is common practice used by persons ordinarily
skilled in the art when considering reaction, the Reagent has a large space in the path of
a nucleophilic agent (substance subjected to reaction). Therefore, it is clear that reaction
with the Steroid Starting Material easily proceeds and that the steroid ring structure does
not become a steric obstruction to reaction with the Reagent at all.
e. Then, Exhibit Otsu 9 Document also describes the step of opening the ring of an
epoxy group of an epoxy ether compound obtained by reaction of butanol and theReagent in an intended direction with a reducing agent. It also describes that a side
chain that is identical with a Maxacalcitol Side Chain is formed if said ring is opened. It
is obvious that the side chain formed by using isopropanol in place of butanol will havethe same structure (Maxacalcitol Side Chain) if the ring of the epoxy group is opened.
Therefore, a person ordinarily skilled in the art should be considered to be motivatedto synthesize the epoxide compound of the Corrected Invention based on the idea thatepoxy alkylation reaction between the Reagent and the Steroid Starting Material ishighly likely to proceed with high degree of probability (Exhibit Otsu 39A Written
Opinion).
C. Regarding the allegation of the appellee(A) Regarding whether a person ordinarily skilled in the art can easily conceive of theidea of using an epoxide compound wherein the hydroxymethyl group of the epoxide
compound indicated in Figure 9 in Exhibit Otsu 14 Document is replaced with a methylgroup
The appellee alleges that there is no reason for focusing attention only on the
reduction reaction of the epoxy substance of Exhibit Otsu 14 Invention because theKatsuki-Sharpless reaction is used due to the existence of two kinds of different stericconfigurations for the vitamin D derivatives that are the objective substances of Exhibit
Otsu 14 Invention. However, both of these vitamin D derivatives are very similar to a
Maxacalcitol Side Chain in terms of their structure, and are obtained in a good yield by
the opening of the ring of the epoxy group. Therefore, a person ordinarily skilled in theart can conceive of application to the synthesis of maxacalcitol by focusing on either ofthese derivatives. In addition, a person ordinarily skilled in the art can easily understandthe purpose of using the Katsuki-Sharpless reaction in Exhibit Otsu 14 Document, andhe/she can understand that the issue in terms of steric configuration does not arise inrelation to maxacalcitol and that it is possible to efficiently prepare maxacalcitol byusing only one kind of precursor epoxide compound. Therefore, the existence of two

36

kinds of isomers in Figure 9 does not reduce the easiness of conceiving of the idea
alleged by the appellants.
In addition, the appellee alleges that it is straightforward to replace the reagent withprenyl bromide in the case of applying Exhibit Otsu 14 Invention to the synthesis of
maxacalcitol. However, retrosynthesis is applied in order to synthesize an epoxide
compound, which is a precursor, as efficiently as possible, and a person ordinarily
skilled in the art would not bother to adopt a roundabout synthesis process which
comprises a larger number of steps. Therefore, the appellee's allegation is unreasonable.
(B) Regarding the predictability of reaction between the Reagent and the Steroid
Starting Material
The appellee alleges that a person ordinarily skilled in the art cannot predict the
progress of reaction between the Reagent and the Steroid Starting Material, and cites thefollowing as grounds for the allegation: [i] The Reagent can cause a side reaction as it
has three candidates for the reaction point; [ii] The ring of the epoxy group of theReagent can be opened; [iii] It is not possible to predict that reaction proceeds at
Reaction Point 1 mentioned later based on the charge distribution of the Reagent; [iv] It
is not possible to predict that reaction proceeds by direct replacement reaction based on
knowledge about the reactivity of epihalohydrin; [v] The reaction of the Steroid Starting
Material is affected by the solid of the Reagent.
However, regarding [i] and [ii] above, it is clear from Exhibit Otsu 9 Document
itself that reaction proceeds at Reaction Point 1 by direct replacement reaction without
the ring of the epoxy group being opened.
In addition, regarding [iii] above, the appellee's allegation that in the Reagent, boththe carbon atom at the reaction point and a carbon atom next to it are positively charged
is erroneous.
Regarding [iv] above, it is known that in Williamson reaction, epihalohydrin also
reacts at Reaction Point 1 (Exhibit Otsu 58).
Furthermore, regarding [v] above, said fact is nothing more than the knowledge
which the researchers of the appellee personally had, and is not common generaltechnical knowledge. It was well-known as of the Priority Date that the hydroxyl groupof the Steroid Starting Material easily yields SN2 reaction with a variety of alkyl halide
reagents that have molecular weight equivalent to that of the Reagent or have a structure
similar to that of the Reagent (Exhibits Ko 12 and 20 and Exhibits Otsu 18 and 41).
D. As mentioned above, a person ordinarily skilled in the art who intends to find an
efficient manufacturing process for maxacalcitol can easily conceive of all of thefollowing matters: [i] changing the hydroxymethyl group at the end to a methyl group to37

make the anticipated metabolite of maxacalcitol of Exhibit Otsu 14 Invention bemaxacalcitol (Difference 1), [ii] applying the Reagent to the Steroid Starting Material inplace of the reagent of Exhibit Otsu 14 Invention (Difference 2), and [iii] obtaining theepoxide compound of the Corrected Invention by applying the Reagent to the Steroid
Starting Material (Difference 3).
Then, the existence of Exhibit Otsu 9 Document that describes the Reagent builds
further confidence in the possibility of the aforementioned application. The fact that
Exhibit Otsu 9 Document neither describes nor suggests use of the Reagent in place ofthe reagent of Exhibit Otsu 14 Invention does not affect said easiness. In fact, theinventors of the Corrected Invention say that they thought that maxacalcitol could besynthesized by using the Reagent after seeing the reaction of isopropanol of Exhibit
Otsu 9 Document (Exhibit Ko 13 and Exhibit Otsu 24).
Therefore, the Corrected Invention can be easily conceived of by a person ordinarily
skilled in the art based on Exhibit Otsu 14 Invention and the technical matters describedin Exhibit Otsu 9 Document.
(Appellee)
A. The reaction steps of Exhibit Otsu 14 Invention are as indicated in the following
figures.

Potassium hydride(base)
Removal of a THP group

BromideAlcohol at the
20-position (8)Step [ii]Williamson reaction
Step [i]Opening of theepoxy ring

Step [iv]Katsuki-Sharplessasymmetricepoxidation

Compound (having an
OH group at the end of
the side chain)Compound (12)(not maxacalcitol)
Step [v]Epoxy alcohol (18)

Step [iii]Compound (13)(not maxacalcitol)

Opening of theepoxy ring

Step [iv]
Epoxy alcohol (19)38

Step [v]Common features and differences between the Corrected Invention and Exhibit Otsu
14 Invention are as alleged by the appellants, and the inventions differ in the structure of
the end of the side chain subject to introduction and also differ in the reagent used forreaction.
B. The appellants allege that it is easy to use substances obtained by replacing thehydromethyl group of each of Epoxide Compounds (18) and (19) with a methyl groupas the precursor for maxacalcitol, focusing attention on the point that AnticipatedMetabolites (12) and (13), which are the final objective substances, are obtained by the
opening of the ring of the epoxy groups of Epoxide Compounds (18) and (19) in thereaction steps of Exhibit Otsu 14 Invention.
However, the reaction of Epoxide Compounds (18) and (19) is used in the reaction
steps of Exhibit Otsu 14 Invention because special reaction steps, including the
Katsuki-Sharpless reaction, are adopted to make it possible to selectively produce thesteric configurations of the end of the side chain of the Final Objective Substances (12)and (13). That is, whether the final objective substance is (12) or (13) depends onwhether the epoxide compound used is (18) or (19). The reaction does not require a step
involving an epoxide compound without the objective of controlling the steric structure.
On the other hand, as there is no different steric configuration for the end of a
Maxacalcitol Side Chain, there is no reason for focusing attention only on the reduction
reaction of an epoxy substance in the reaction steps of Exhibit Otsu 14 Invention whendeveloping a process for preparing maxacalcitol. The appellants focus attention only on
the reduction reaction of an epoxy substance of Exhibit Otsu 14 Invention based on theafterthought which arose after seeing the Corrected Invention.
Supposing the case of applying Exhibit Otsu 14 Invention to the synthesis of
maxacalcitol while focusing attention on the similarity between the structure of the
anticipated metabolites of Exhibit Otsu 14 Invention and that of maxacalcitol, it isnatural not to replace the hydroxymethyl group bonded to the epoxy group with amethyl group but to change the reagent to be reacted with the starting material (8) inExhibit Otsu 14 Invention to bromide having the structure indicated in the lower rightfigure (prenyl bromide) (Exhibit Otsu 13).

Reagent of Exhibit Otsu 14

39

Prenyl bromideThe reagent in the right figure reacts with the starting material, but it does notproduce an epoxide compound. If the end of the side chain of the objective substancebecomes a Maxacalcitol Side Chain, there is no reason for producing an epoxy
substance by using the Katsuki-Sharpless reaction.
Exhibit Otsu 14 Document does not suggest that an epoxy reagent is used in theWilliamson reaction with the alcohol compound at the 20-position, and it does notcontain any statement suggesting that the ring-opening reaction of an epoxy substance isused in the introduction of a Maxacalcitol Side Chain. The allegation that the Reagent
can be derived from Exhibit Otsu 14 Invention ignores the technical significance of thereaction steps of Exhibit Otsu 14 Invention.
C. Moreover, the reaction between the Reagent and the alcohol compound at the
20-position, like the starting material of the Corrected Invention, had been predicted tobe difficult based on the common general technical knowledge of organic chemistry, as
mentioned below.
(A) Difficulty in prediction on the side of the Reagent
a. The higher the degree of positive charge (δ+) of the reaction point on the R'-X side ofalkyl halide is or the more stable the positive charge is, the more easily the Williamson
reaction, which is the reaction of the Corrected Invention, proceeds (Exhibit Otsu 56).

In terms of the common sense of organic chemistry, when considering the structureof the reagent of the Corrected Invention, both the α carbon atom, which is the reaction
point, and the β carbon atom next to it are supposed to be positively charged because
each is bonded to a negative atom, specifically, Br atom and oxygen atom, respectively,
as indicated in the figure below. However, both of those neighboring carbon atoms are
positively charged and thus repel each other. Therefore, the positive charge of the
carbon atom at the reaction point is difficult to stabilize, and Williamson reaction is also
predicted to be difficult to progress.
Reaction point40

b. In addition, as the Reagent has three candidates for the reaction point, the possibilityof causing a side effect is predicted.
Reaction Point 2

Reaction Point 3

Reaction Point 1

c. Furthermore, an epoxide compound having an epoxy group in its molecule isgenerally rich in reactivity, and its ring is easy to open. Therefore, the opening of thering by reaction is predicted.
d. According to many studies concerning epihalohydrin, whose structure is similar tothat of the Reagent, epihalohydrin causes the opening of the ring of an epoxy group byreaction with a nucleophilic reagent in many cases (direct replacement reaction occurs
in few cases). The conditions and route of such reaction (whether or not direct
replacement reaction occurs) are difficult to predict (Exhibit Ko 31). It is impossible topredict the direct replacement reaction of the Reagent from the knowledge of
epihalohydrin.
(B) Difficulty in prediction on the side of the alcohol compound at the 20-position
On the other hand, the alcohol compound at the 20-position is sensitive to the effectof the solid (bulkiness of the position of the ring of the reagent, etc.) of the reagent
which is the reaction partner. It is not possible to directly introduce a Maxacalcitol Side
Chain into the alcohol compound at the 20-position, and reaction between the alcoholcompound at the 20-position and Compound 9 of Exhibit Ko 13 or Reagent 1 of Exhibit
Ko 12 mentioned later does not proceed at all. The alcohol compound at the 20-position
is presumed to have a steric hindrance that hinders its reaction with the Williamson
reaction reagent that has a structure into which a Maxacalcitol Side Chain can be
introduced.
D. Exhibit Otsu 9 Document describes the consequence that the prediction based on thecommon general technical knowledge of organic chemistry mentioned in C. above is
not applicable to reaction between the Reagent and a low-molecular-weight alcohol,such as isopropanol. However, the reason why reaction between the starting material
and reagent of Exhibit Otsu 9 Document proceeds has not been clarified, and Exhibit
Otsu 9 Document does not include any statement that explains the reason in anunderstandable manner. Moreover, the reaction yield (40.6 to 76.4%) and reaction
conditions (requiring a heated reflux at 40 to 80°C for eight to 10 hours) of Exhibit Otsu

41

9 Document suggest that the Reagent has a steric hindrance. In that case, the Reagent
has a reason for having people predict the difficulty of reaction in general. On the other
hand, Exhibit Otsu 9 Document also suggests the existence of an action that promotes
reaction, which goes beyond an action that makes reaction difficult, in reaction withlow-molecular-weight alcohol, though the reason therefor is unknown.
However, Exhibit Otsu 9 Document does not have people predict reactivity inrelation to reaction with the alcohol compound at the 20-position, whose structure
significantly differs from that of low-molecular-weight alcohol. Therefore, it isreasonable to predict that reaction with the Reagent is also difficult, or to consider thatwhether or not the alcohol compound at the 20-position reacts with the Reagent is
unknown without conducting experiments. In addition, there is no knowledge thatserves as the basis for the predictability of the reactivity of the Reagent other thanExhibit Otsu 9 Document, and it is also difficult to predict the reaction of the Corrected
Invention from the perspective of the Reagent.
In the Corrected Invention, actual experiments revealed that a combination of thealcohol compound at the 20-position causes reaction in a very good yield, despite theaforementioned prediction based on the common general technical knowledge. In
consideration of the purpose of the patent system, a reaction that is not known toproceed without experiments should be evaluated as an invention involving an inventive
step only if it is found to be reactive by actual experiments.
(2) Regarding the lack of an inventive step by citing Exhibit Ko 12 Document as theprimarily cited document (Ground for Invalidation B)(Appellants)
A. In a paper written by Noboru Kubodera and four other authors titled "Synthetic
studies of vitamin D3 analogues VIII" (Chem. Pharm. Bull., 1986, 34 (10), 4410;
Exhibit Ko 12; hereinafter referred to as "Exhibit Ko 12 Document"), it is stated thatalkylation reaction did not occur though Compound 9, which is the same starting
material as that of the Corrected Invention (Steroid Starting Material), and"1-bromo-3,3-ethylenedioxybutane" (hereinafter referred to as "Exhibit Ko 12 Reagent
1") as a reagent were used for the purpose of the synthesis of maxacalcitol.
The aforementioned process for preparing maxacalcitol described in Exhibit Ko 12
Document (hereinafter referred to as "Exhibit Ko 12 Invention") and the Corrected
Invention are identical with each other in the requirements for the objective substance,
the starting material, and recovery, but differ in the reagent (Difference 1) and also
differ in the intermediate and the reduction treatment to ring opening step (Difference
2).

42

B. The aforementioned Difference 1 can be easily overcome as mentioned below.
(A) As the appellants' allegation in (1) above, obtaining an efficient process for
preparing maxacalcitol was naturally a technical problem facing a person ordinarily
skilled in the art as of the Priority Date (Exhibit Ko 12 and Exhibit Otsu 14).
In addition, alkylation of the hydroxyl group at the 22-position of the Steroid
Starting Material by an alkylation reagent in preparing maxacalcitol was the art that had
already been commonly used as of the Priority Date (Exhibit Ko 12 and Exhibits Otsu
18 and 14). As of the Priority Date, a person ordinarily skilled in the art who was
engaged in studies of the aforementioned technical problem only had to find analkylation reagent that could alkylate the hydroxyl group at the 22-position of thesteroid compound in a good yield.
(B) In Note 10 in Exhibit Ko 12 Document, the following is stated as a reason for a
failure in synthesis using Exhibit Ko 12 Reagent 1: "It may be due to the bulkiness of
1-halo-3,3-ethylenedioxybutane." This statement suggests that among Exhibit Ko 12
Regent 1 (figure below), one wherein five-membered ring cyclic ether is less bulky canbe expected to cause the progress of alkylation reaction with the Steroid Starting
Material (Compound 9).

(C) On the other hand, a Maxacalcitol Side Chain has a structure wherein four-carbon
straight alkyl is bonded to an ether group. Therefore, the reagent used for introducing a
Maxacalcitol Side Chain is also required to be one whose straight chain structure has
four carbons.
Then, Exhibit Ko 12 Document describes that maxacalcitol was obtained at the yieldof 9% by reaction between the Steroid Starting Material and "4-bromo-1-butene"(hereinafter referred to as "Exhibit Ko 12 Reagent 2") indicated in the figure below.

In that case, a person ordinarily skilled in the art can conceive of using and ismotivated to use a compound which has a cyclic structure but is not bulky while
maintaining a four carbon straight alkyl structure, specifically, a compound whose
number of elements that constitute the ring of the cyclic part is reduced to reduce thefive-membered ring cyclic ether part, as the reagent.
Then, it is possible to find Exhibit Ko 9 Document, which places the Reagent as acompound that meets the aforementioned conditions, by examining compounds that43

were publicly known at that time.
(D) The content described in Exhibit Otsu 9 Document is as the appellants' allegation in
B.(D)d. in (1) above. The alkylation reaction described in Exhibit Ko 12 Document andthe reaction between the Reagent and alcohol in the presence of alkali metal, alkoxide,
as described in Exhibit Otsu 9 Document have commonality in that they are arts relating
to SN2 reaction. Therefore, the Reagent is predicted to react well with the Steroid
Starting Material.
In addition, as it is obvious from a three-dimensional model, in Exhibit Ko 12
Reagent 1, the five-membered ring serves as a wall to block the path of the nucleophilic
agent. Therefore, the oxygen atom of the Steroid Starting Material cannot get closer tothe reagent, and SN2 reaction does not proceed due to this steric hindrance. On the other
hand, the Reagent has a large space in the path of the nucleophilic agent, and the epoxy
group does not block the path of the Steroid Starting Material. Therefore, thenucleophilic agent can get closer to the back side of the carbon at the reaction point.
Therefore, a person ordinarily skilled in the art who sees the statements in Note 10 in
Exhibit Ko 12 Document can understand that the steric hindrance is overcome for theReagent and is also strongly motivated to use the Reagent for the reaction in this regard.
(E) Then, as the appellants' allegation in B.(D)d. in (1) above, Exhibit Otsu 9 Document
also describes that an epoxide compound obtained by reacting butanol and the Reagent
was made into a Maxacalcitol Side Chain by treating the epoxy group with a reducing
agent. Furthermore, it is possible to reduce the number of steps compared to Exhibit Ko
12 Invention, which goes through a step involving a ketone body, by introducing an
epoxy group. Therefore, a person ordinarily skilled in the art would use the Reagent.
(F) In addition, Exhibit Ko 12 Document does not include any statement or fact thathinders the use of the Reagent in place of Exhibit Ko 12 Reagent 1.
(G) Therefore, it is natural for a person ordinarily skilled in the art who recognizes thetechnical problem mentioned in (A) above to try to react the Steroid Starting Material of
Exhibit Ko 12 Document with the Reagent described in Exhibit Ko 9 Document basedon the suggestion of Exhibit Ko 12 Document.
C. The aforementioned Difference 2 (difference in the intermediate and the reduction
treatment to ring-opening step) is automatically overcome if Difference 1 (difference inthe reagent) is overcome. In addition, it was widely known prior to the Priority Date that
it is possible to produce the same side chain as a Maxacalcitol Side Chain by opening
the ring of the epoxy group of an epoxy group-introduced steroid compound with areducing agent. Consequently, Difference 2 can be easily overcome.
D. Therefore, the Corrected Invention is one which a person ordinarily skilled in the art

44can easily conceive of based on Exhibit Ko 12 Invention and Exhibit Ko 9 Document.
(Appellee)
A. As alleged by the appellants, the Corrected Invention and Exhibit Ko 12 Inventiondiffer in the reaction reagent (Difference 1) and also completely differ in theintermediate and the step of forming a Maxacalcitol Side Chain by opening the ring of
the epoxy group (Difference 2).
B. The appellants allege that a person ordinarily skilled in the art who was engaged instudies of an efficient process for preparing maxacalcitol only had to find an alkylation
reagent which can alkylate the hydroxyl group at the 22-position of a steroid compoundin a good yield. However, a process which the appellee actually used for the preparationof a curative medicine in a clinical test as the improved technology of Exhibit Ko 12
Invention is not the Williamson reaction that is the same as Exhibit Ko 12 Invention,
which is alkylation using an alkylation reagent, but a process called Michael process.
Therefore, said allegation is based on an afterthought that arose after seeing theCorrected Invention. There are many alkylation reagents, but the Reagent is the only
alkylation reagent that can be used for the industrial production of maxacalcitol.
C. The "bulkiness" referred to in Note 10 in Exhibit Ko 12 Document is mentioned incomparison
withalkylation
reaction
between"1α,3β-bis(tetrahydropyranyloxy)-5-androstene-17β-ol"and"1-chloro-4,4-ethylenedioxypentane" (hereinafter referred to as "Exhibit Ko 12 Reagent
3"). It is presumed to be based on the degree of distance of the five-membered ring fromthe reaction point of the introduction of a side chain in the starting material. Originally,
the aforementioned alkylation reaction differs from the reaction of Exhibit Ko 12
Invention in the structure of the reaction point on the side of alcohol, which is thestarting material. Therefore, there is no reason for putting emphasis on Note 10.
Moreover, in Exhibit Ko 12 Document, the reaction using Exhibit Ko 12 Reagent 1,
which is a bulky reagent having a five-membered ring, failed, and the yield of thereaction using Exhibit Ko 12 Reagent 2, which does not have any cyclic structure, as thereagent was 9%. Both of those reactions do not have satisfactory reactivity. Therefore, aperson ordinarily skilled in the art who sees Exhibit Ko 12 Document normally thinksof another reagent, and the appellants' allegation that "a person ordinarily skilled in theart considers that a reaction using a compound which has a cyclic structure but is notbulky goes well" is incomprehensible.
D. It is impossible to predict from Exhibit Ko 9 Document that a reaction between the
Reagent and high-molecular-weight alcohol, like the Steroid Starting Material of
Exhibit Ko 12 Document, proceeds, as the appellee's allegation in D. in (1) above.

45

E. As mentioned above, there is no reason for the appellants' allegation that a person
ordinarily skilled in the art could have easily conceived of the structure of the Corrected
Invention pertaining to differences between the Corrected Invention and Exhibit Ko 12
Invention.
(3) Regarding the lack of an inventive step by citing Exhibit Otsu 4 Document as theprimarily cited document (Ground for Invalidation C)
The parties' allegations concerning Ground for Invalidation C are as briefly
indicated in No. 3, 7. in "Facts and reasons" in the judgment in prior instance. Therefore,
the relevant part is cited (however, in the judgment in prior instance pertaining to thecitation, the terms "Ground for Invalidation 2," "Exhibit Otsu 4-2," and "Exhibit Otsu 9"
are deemed to be replaced with "Ground for Invalidation C," "Exhibit Otsu 4
Document," and "Exhibit Otsu 9 Document," respectively; hereinafter the same shallapply in the case of citation).
No. 4 Court decisionThis court also determines that the Appellant's Process is equivalent to the Corrected
Invention and that the Patent Pertaining to the Corrected Invention is not recognized as
one that should be invalidated by a trial for patent invalidation. The reasons therefor are
as follows.
1. Regarding whether the Appellant's Process is equivalent to the Corrected Invention(1) Regarding the five requirements of the doctrine of equivalents and burden of proof
A patentee shall have the exclusive right to work the patented invention as abusiness (main clause of Article 68 of the Patent Act). The technical scope of a patented
invention shall be determined based upon the statements in the scope of claims attachedto the application (Article 70, paragraph (1) of said Act). An applicant for a patent shallstate all matters necessary to specify the invention for which he/she requests the grant ofa patent in the scope of claims (Article 36, paragraph (5) of said Act). Therefore, thestatements in the scope of claims function to publicly notify third parties of the scope ofthe exclusive right of the patent. Consequently, the technical scope of a patented
invention is in principle defined by the literal interpretation of the structure stated in thescope of claims.
However, even if, within the structure stated in the scope of claims, there is a partwhich is different from a product manufactured, etc. or a process used by the other party(hereinafter referred to as the "subject product, etc."), it is reasonable to understand thatthe subject product, etc. falls under the technical scope of the patented invention as anequivalent to the structure stated in the scope of claims if the following requirements are46

fulfilled: [i] said part is not the essential part of the patented invention; [ii] even if said
part is replaced with a part in the subject product, etc., the purpose of the patented
invention can be achieved and the same function and effect can be obtained; [iii] aperson ordinarily skilled in the art to which the invention pertains (a person ordinarily
skilled in the art) could have easily conceived of the aforementioned replacement at thetime of the manufacturing, etc. of the subject product, etc.; [iv] the subject product, etc.
is neither identical with publicly known art at the time of the filing of the patentapplication for the patented invention nor is one which a person ordinarily skilled in theart could have easily presumptively conceived of at the time of said filing based on such
publicly known art; and [v] there are no special circumstances, such as the fact that the
subject product, etc. falls under those that were intentionally excluded from the scope ofclaims in the patent application procedures for the patented invention (hereinafter
requirements [i] to [v] above are referred to as the "First Requirement" to the "Fifth
Requirement" in order of precedence). This is because [1] it is extremely difficult toforesee all kinds of infringements which may occur in the future and formulate thescope of the claims in the description at the time of filing a patent application, and if
another person is able to easily avoid injunction and other exercise of rights by thepatent holder by only replacing part of the structure stated in the scope of claims by thesubstance or art, etc. which came to be known after the filing of the patent application, it
will greatly reduce incentives for invention in society in general, which is not only
against the purposes of the Patent Act, i.e. contributing to the development of industry
through the protection and encouragement of inventions, but would be against social
justice and the ideas of fairness. [2] Taking this into account, it is reasonable tounderstand that the substantive value of the patented invention extends to the art whicha third party can easily conceive of as one that is substantially identical with thestructure stated in the scope of claims based on said structure and that third parties
should foresee this. [3] On the other hand, concerning arts which were publicly knownat the time of the filing of the patent application for the patented invention or arts which
a person ordinarily skilled in the art could have easily presumptively conceived of basedon these arts, no one could have obtained a patent; therefore, such arts cannot be foundto be within the technical scope of the patented invention. [4] Furthermore, concerning
arts which the patentee had once acknowledged not to fall under the technical scope of
the patented invention or arts in relation to which he/she had behaved as if he/she had
objectively acknowledged so, e.g. where the applicant intentionally excluded art fromthe scope of claims in the patent application procedures, the patentee is not entitled toclaim otherwise afterwards, since this is against the doctrine of estoppel (Supreme Court

47

Judgment on the "Ball spline bearing" Case).
Regarding the burden of alleging and proving the fulfillment of the First to Fifth
Requirements, it is reasonable to understand as follows, taking into account that thedoctrine of equivalents should be applied within the scope of those that are found to beeasily conceived of by a person ordinarily skilled in the art as one that is substantially
identical with the statements in the scope of claims beyond the scope of the literalinterpretation of said statements: a person who alleges that the subject product, etc. isequivalent to a patented invention should be considered to have the burden of allegationand proof for the First to Third Requirements, which are the facts required for the
subject product, etc. to be recognized as falling within said scope, while a person who
denies the application of the doctrine of equivalents in relation to the subject product,
etc. has the burden of allegation and proof for the Fourth and Fifth Requirements, which
are related to the cases where the doctrine of equivalents should not be applied, even if
the subject product, etc. is within the aforementioned scope.
(2) Differences between the Corrected Invention and the Appellant's Process
As mentioned in No. 2, 2.(7)(D) above, the Appellant's Process fulfills Constituent
Features [A], [B-2], [D], and [E] of the Corrected Invention, but it does not fulfill
Constituent Features [B-1], [B-3], and [C] of the Corrected Invention in that Starting
Material A and Intermediate C in said process are not cis-form compounds having avitamin D structure but are trans-form compounds having a vitamin D structure, which
are the geometric isomers of said cis-form compounds. Therefore, the fulfillment of therequirements for the doctrine of equivalents is determined below in a sequential order todetermine whether the Appellant's Process using trans-form compounds having avitamin D structure as the starting material and the intermediate can be considered to beequivalent to the case of using cis-form compounds having a vitamin D structure as thestarting material and the intermediate in the Corrected Invention.
(3) Regarding the First Requirement of the doctrine of equivalents (non-essential part)
A. Regarding the finding of the essential partThe substantial value of an invention which the Patent Act intends to protect exists inthe disclosure, with a specific structure, to society of a means for solving a technicalproblem that could not have been solved by prior art, which is based on a unique
technical idea that is not seen in prior art. Therefore, the essential part of a patented
invention should be understood as the characteristic part which constitutes a unique
technical idea that is not seen in prior art in the statements in the scope of claims of thepatented invention.
The aforementioned essential part should be found by first understanding the48

problem to be solved and means for solving the problem of the patented invention (seeArticle 36, paragraph (4) of the Patent Act and Article 24-2 of the Ordinance for
Enforcement of the Patent Act) and its effect (purpose and structure and its effect; see
Article 36, paragraph (4) of the Patent Act prior to amendment by Act No. 116 of 1994)
based on the statements in the scope of claims and the description, and then determining
the characteristic part which constitutes a unique technical idea that is not seen in prior
art in the statements in the scope of claims of the patented invention. That is, taking into
account that the substantial value of a patented invention is defined depending on the
degree of contribution in comparison with prior art in the relevant technical field, theessential part of a patented invention should be found based on the statements in thescope of claims and the description, in particular, through comparison with prior art
stated in the description. [i] If the degree of contribution of the patented invention isconsidered to be more than that of prior art, the patented invention is found as a genericconcept in relation to part of the statements in the scope of claims (as mentioned later in
C. and D.; the Corrected Invention is an example of such a case). [ii] If the degree ofcontribution of the patented invention is evaluated as not much more than prior art, thepatented invention is found to have almost the same meaning as stated in the scope ofclaims.
However, if the statement of the problem, which is described as one that prior art
could not solve, in the description is objectively insufficient in light of prior art as of thefiling date (or the priority date; hereinafter the same applies in (3) in this section), acharacteristic part which constitutes a unique technical idea of the patented invention
that is not seen in prior art should be found also in consideration of prior art that is notstated in the description. In such cases, the essential part of the patented invention iscloser to the statements in the scope of claims compared to the cases where it is foundonly based on the statements in the scope of claims and the description, and the scope of
application of the doctrine of equivalents is considered to be narrower.
In addition, in determining the fulfillment of the First Requirement, that is, whether
a difference from the subject product, etc. is a non-essential part, it is not appropriate to
first divide the constituent features stated in the scope of claims into essential parts andnon-essential parts and then consider that the doctrine of equivalents is not applicable toall of the constituent features that fall under essential parts, but it is necessary to first
determine whether the subject product, etc. commonly has the essential part of thepatented invention determined as mentioned above and then consider a difference not tobe an essential part if the subject product, etc. is recognized as having said essential part.
Even if the subject product, etc. has a difference other than the characteristic part which49

constitutes a unique technical idea that is not seen in prior art, this fact does not becomea reason for denying the fulfillment of the First Requirement.
B. Statements in the Corrected Description
The following is stated in the "detailed explanation of the invention" section in the
Corrected Description (Exhibit Ko 15; incidentally, line numbers cited at the end ofeach sentence do not include chemical formulas as lines).
(A) "Background of the invention""Vitamin D and its derivatives have important physiological functions. For example,
1α,25-dihydroxy vitamin D3 exhibits a broad range of physiological functions, such as
calcium
metabolism-controlling
activity,
growth-inhibiting
activity,differentiation-inducing activity on cells, such as tumor cells, and immune-controlling
activity. However, vitamin D3 derivatives exhibit undesirable side effects, such as
hypercalcemia.
Novel vitamin D derivatives have been developed to retain effectiveness in thetreatment of specific diseases while reducing associated side effects.
For example, Publication of Unexamined Patent Application No. 1986-267550(issued on November 27, 1986) discloses a 9,10-seco-5,7,10(19)-pregnatriene derivative,
which exhibits an immune-controlling activity and differentiation-inducing activity on
tumor cells. In addition, Publication of Unexamined Patent Application No.
1986-267550 (issued on November 27, 1986) also discloses two kinds of processes for
preparing the final end product, one using pregnenolone and the other using
dehydroepiandrosterone as the starting material.
1α,25-dihydroxy-22-oxavitamin D3 (OCT), that is, the 22-oxa analog of
1α,25-dihydroxy vitamin D3 has potent in vitro differentiation-inducing activities with
low in vivo calcemic liability. OCT is being clinically investigated as a candidate fortreatment of secondary hyperparathyroidism and psoriasis.
Publication of Unexamined Patent Application No. 1994-072994 (issued on March
15, 1994) discloses a 22-oxacholecalciferol derivative and a process for the preparation
thereof. It discloses a process for preparing an oxacholecalciferol derivative which
comprises steps of reacting a pregnene derivative having a hydroxyl group at the
20-position with a dialkylacrylamide compound to obtain an ether compound and thenreacting the thus-obtained ether compound with an organometal compound to obtain thedesired compound.
Publication of Unexamined Patent Application No. 1994-080626 (issued on March
22, 1994) discloses a 22-oxavitamin D derivative. It also discloses a process which
comprisesastepofreacting50

1α,3β-bis(tert-butyldimethylsilyloxy)-pregne-5,7-diene-20(S or R)-ol as a starting
material with an epoxide in the presence of a base to obtain a compound having an etherbond at the 20-position.
In addition, Publication of Unexamined Patent Application No. 1994-256300 (issued
on September 13, 1994) and Kubodera et al. (Bioorganic & Medicinal Chemistry
Letters, 4(5): 753-756, 1994) disclose a process for stereospecifically preparing an
epoxy
compoundwhich
comprises
stepsofreacting
1α,3β-bis(tert-butyldimethylsilyloxy)-pregna-5,7-diene-20(S)-ol
with
4-(tetrahydropyran-2-yloxy)-3-methyl-2-butene-1-bromide to obtain an ether compound,deprotecting it, and subjecting the deprotected ether compound to Sharpless oxidation.
However, the aforementioned processes require more than one step for introducing an
ether bond and an epoxy group into a side chain of a steroid group and therefore, resultin low yield of the desired compound.
Furthermore, none of the aforementioned documents disclose a synthesis process inwhich an alcohol compound is reacted with an epoxy hydrocarbon compound having aneliminating group at its end, thereby forming an ether bond. Also, the aforementioned
documents do not disclose a bicyclo [4.3.0] nonane structure (hereinafter referred to as a
"CD ring structure" in this description), a steroid structure, or a vitamin D structure,each having an ether bond and an epoxy group at a side chain." (line 6 of page 15 to line
13 of page 16)(B) "Detailed explanation of the invention"a. "The present invention provides a process for preparing a compound having thefollowing structure:(in the formula, n is an integer from 1 to 5; each of R1 and R2 independently is
optionally substituted C1-C6 alkyl; each of W and X is independently hydrogen or
C1-C6 alkyl; Y is O, S or NR3 where R3 is hydrogen, C1-C6 alkyl or a protective group;
and Z is:

51

,

, or

where each of R4, R5, R8, … and R17 independently is hydrogen, a substituted or
unsubstituted lower alkyloxy, amino, alkyl, alkylidene, carbonyl, oxo, hydroxyl, or
protected hydroxyl; and each of R6 and R7 independently is hydrogen, substituted or
unsubstituted lower alkyloxy, amino, alkyl, alkylidene, carbonyl, oxo, hydroxyl,
protected hydroxyl, or together constitute a double bond); which comprises:(a) the step of reacting a compound having the following structure:(in the formula, W, X, Y and Z are as defined above)in the presence of a base, with a compound having the following structure:

52

or

(in the formula, n, R1, and R2 are as defined above, and E is an eliminating group)
to prepare a compound; and(b) the step of recovering the compound so prepared. …
The process for preparing a compound having the following structure:

is novel and is useful for the synthesis of vitamin D derivatives which can have avariety of physiological activities, such as differentiation-inducing activity andgrowth-inhibiting activity on cells." (line 6 of page 24 to the second line from thebottom of page 25).
b. "The present invention also provides a compound having the following structure:

,

, or

(in the formula, Z represents a CD ring structure, a steroid structure or a vitamin D
structure, each of which may optionally have one or more protected or unprotected53

substituents and/or one or more protective groups). Each of the CD ring structure,
steroid structure, and vitamin D structure for the present invention particularly means astructure as described below, any ring of which may optionally have one or moreunsaturated bonds. In the steroid structure, one having one or two unsaturated bonds are
preferred, and 5-ene steroid compound, 5,7-diene steroid compound, or a protectedcompound thereof, are particularly preferred.
CD ring structure:

Steroid structure:

Vitamin D structure:

The substituents on Z, which is the CD structure, steroid structure, or vitamin D
structure, are not particularly limited but may be exemplified by a hydroxyl group, a
substituted or unsubstituted lower alkyloxy group, …and an oxo group (=O), with ahydroxyl group being preferred. These substituents may be protected. …
Examples of a protective group for an unsaturated bond in the steroid structure
include 4-phenyl-1,2,4-triazoline-3,5-dione and diethyl maleate. An example of adducts
having such protective group is the following: …
Furthermore, the vitamin D structure may be protected by addition of SO2.
Examples of such protected vitamin D structures are given below:." (first line from the bottom of page 25 to line 2 of page 28)c. "An outline of the reaction disclosed in this description for the preparation of thecompound of Formula I is shown in the following Reaction Scheme A.
Reaction Scheme A:

54

Some of the compounds which are used as a starting compound in the
aforementioned process according to the present invention are publicly known
compounds. For example, when "Y" is O, the following can be used as the starting
compounds: the lα,3β-bis(tert-butyldimethylsilyloxy)-pregna-5,7-diene-20(S)-ol as
described in Publication of Unexamined Patent Application No. 1986-267550 (issued on
November 27, 1986); the 9,10-seco-5,7,10(19)-pregnatriene-1α,3β,20β-triol optionallywith the hydroxyl group being protected as described in Publication of Unexamined
Patent Application No. 1986-267550 (issued on November 27, 1986) and International
Patent Publications WO 1990/09991 (September 7, 1990) and WO 1990/09992(September
7,1990);
theoctahydro-4-(t-butyldimethylsilyloxy)-7-methyl-1H-indene-1-ol described in J. Org.
Chem., 57, 3173 (1992); and the octahydro-4-(acetyloxy)-7-methyl-1H-indene-1-ol as
described in J. Am. Chem. Soc., 104, 2945 (1982)." (second line from the bottom of
page 29 to line 10 of page 30)
d. "The present invention relates to a process for preparing vitamin D or steroid
derivatives via the novel intermediates described above in this description. An outline ofthis reaction is shown in the following Reaction Scheme B.
Reaction Scheme B:

Step (1)

Step (2)The reaction in Step (1) of the aforementioned two-step reaction according to thepresent invention can be carried out in the same way as in the process of Reaction
Scheme A, which was already described in this description.
The reaction in Step (2) is a reaction to open the epoxy ring in the epoxide
compound obtained in Step (1) and it is carried out using a reducing agent. The

55

reducing agent which can be used in Step (2) is such that it is capable of opening thering of an epoxide compound obtained in Step (1) to create a hydroxyl group, preferably
capable of selectively forming a tertiary alcohol." (lines 5 to 12 of page 39)
e. "The following Reaction Scheme C shows reaction routes using the compounds andprocesses of the present invention. Processes for the synthesis of a vitamin D compoundfrom the corresponding steroid compound can be carried out by a conventional process
such as ultraviolet irradiation and thermal isomerization. Processes for the synthesis of avitamin D compound from the corresponding CD ring compound are also conventional.
Such processes are described in, for example, E. G. Baggiolini et al., J. Am. Chem. Soc,
104, 2945-2948 (1982) and Wovkulich et al., Tetrahedron, 40, 2283 (1984). It should beunderstood that a part or all of the processes shown in Reaction Scheme C are embraced
within the present invention.
Reaction Scheme C:(in the formula, W, X, Y, O, R1, and R2 are the same as defined above, and any ring of
the structure may optionally have one or two unsaturated bonds)." (line 7 of page 42 toline 3 of page 43)
C. Content of the Corrected Invention(A) According to the statements in B. above, the following is recognized in relation to
the Corrected Invention.
a. The Corrected Invention relates to a process for preparing a compound that is useful56

for the synthesis of vitamin D derivatives which can have a variety of physiologicalactivities, such as differentiation-inducing activity and growth-inhibiting activity on
cells.
b. In the past, 1α,25-dihydroxy-22-oxavitamin D3 (maxacalcitol), which is the 22-oxa
analog (derivative in which the atom at the 22-position is replaced with an oxygenatom) of calcitriol (1α,25-dihydroxy vitamin D3), etc. had been developed as novelvitamin D derivatives.
Publication of Unexamined Patent Application No. 1986-267550 (Exhibit Ko 1-2;
hereinafter referred to as "Exhibit Ko 1 Publication") is a document that disclosed a
9,10-seco-5,7,10(19)-pregnatriene derivative, which contains maxacalcitol as a novel
substance, and a process for preparing it. Said process is a process for preparing
maxacalcitol, etc. by reacting the alcohol compound at the 20-position of a steroid ring
structure with 4-bromo-1-butene as a reagent to introduce a side chain (which is not a
Maxacalcitol Side Chain) at the 20-position, oxidizing it, reacting it with anotherreagent, an organometal compound (methylmagnesium bromide), and finally carrying
out ultraviolet irradiation and thermal isomerization.
c. After the disclosure of the manufacturing process described in Exhibit Ko 1
Publication, processes for preparing a 22-oxa analog by reacting the alcohol compoundat the 20-position of a steroid ring structure with a reagent to form a side chain were
described in [i] Publication of Unexamined Patent Application No. 1994-72994 (Exhibit
Otsu 35), [ii] Publication of Unexamined Patent Application No. 1994-80626 (Exhibit
Otsu 36), and [iii] Publication of Unexamined Patent Application No. 1994-256300(Exhibit Otsu 46 Publication; incidentally, the process described in this publication is
the same as one indicated in Figure 9 of Exhibit Otsu 14 Document) (however, as
mentioned below, out of these processes, the process described in [i] is the only process
for preparing a compound having a Maxacalcitol Side Chain).
The process described in [i] above is a process for preparing maxacalcitol by firstreacting the alcohol compound at the 20-position of a steroid ring structure with adialkylacrylamide compound to introduce a side chain (which is not a Maxacalcitol Side
Chain) at the 20-position by an ether bond and furthermore reacting it with anorganometal compound to form a Maxacalcitol Side Chain.
The process described in [ii] above is a process for preparing a 22-oxavitamin D
derivative (which does not have a Maxacalcitol Side Chain) by first reacting the alcoholcompound at the 20-position of a steroid ring structure with an epoxide compound in
the presence of a base to introduce a side chain (an epoxy group is not formed in theside chain) by an ether bond and then removing a protective group of the side chain.

57

The process described in [iii] above is a process for preparing a
26-hydroxy-22-oxavitamin D derivative (which differs from a Maxacalcitol Side Chainin that one of the methyl groups at the end thereof is a hydroxymethyl group), by firstreacting the alcohol compound at the 20-position of a steroid ring structure with
4-(tetrahydropyran-2-yloxy)-3-methyl-2-butene-1-bromide to introduce a side chain(which is not a Maxacalcitol Side Chain) at the 20-position by an ether bond, removing
the protective group of the side chain, and furthermore forming an epoxy group at theside chain by the Katsuki-Sharpless oxidation reaction to finally open the ring of theepoxy group.
However, the processes described in [i] and [ii] above are not those involving
introduction of an epoxy group into a side chain having a steroid ring structure. In
addition, the process described in [iii] above is not one involving a reaction with an
epoxy hydrocarbon compound, and requiring more than one step for introducing an
ether bond and an epoxy group into a side chain having a steroid ring structure. That is,none of the aforementioned publicly known documents, including Exhibit Ko 1
Publication, discloses either a synthesis process wherein the alcohol compound at the
20-position is reacted with an epoxy hydrocarbon compound having an eliminatinggroup at its end to form an ether bond or a process for introducing an ether bond and an
epoxy group into a side chain having a steroid ring structure or a vitamin D structure
through one step, in relation to processes for preparing a 22-oxa analog (22-oxavitamin
D derivative), let alone maxacalcitol.
d. The problem to be solved of the Corrected Invention is to provide a novel
manufacturing process which has not been disclosed in prior art as mentioned in c.
above, as a process for preparing vitamin D or steroid derivatives having a Maxacalcitol
Side Chain (process for introducing a Maxacalcitol Side Chain into a compound having
a vitamin D structure or a steroid ring structure). As a specific means for solving the
problem, the Corrected Invention adopts a process for preparing a vitamin D or steroid
derivatives having a Maxacalictol Side Chain, which comprises the step of reacting thealcohol compound at the 20-position of a vitamin D structure or a steroid ring structure(compound of Constituent Feature [B-1]), in the presence of a base, with an epoxyhydrocarbon compound having an eliminating group at its end (reagent of Constituent
Feature [B-2]) to synthesize an epoxide compound having a steroid ring structure or avitamin D structure which has an ether bond and an epoxy group at the side chain(intermediate of Constituent Feature [B-3]) and the step of treating it with a reducing
agent to open the ring of the epoxy group of the side chain, thereby forming a hydroxyl
group (incidentally, out of the two kinds of reagents stated in Constituent Feature [B-2],

58

one that does not contain an epoxy group forms the same structure as the other one that
contains an epoxy group in the presence of a base).
e. Incidentally, out of the carbon skeletons of "Z" of the starting material, intermediate,
and objective substance of the Corrected Invention, all of those having a vitamin D
structure are cis forms. However, the carbon skeleton of Z "may optionally have one ormore protected or unprotected substituents and/or one or more protective groups"(Constituent Feature [A-6]). As mentioned later in (7)B.(B)c., if SO2 is added to a
cis-form vitamin D structure as a protective group, the double bond at the 5-position of
the vitamin D structure is lost and the rotational hindrance is eliminated, and thestructure ceases to be a geometric isomer. The "Z" of the Corrected Invention also
literally includes vitamin D structures for which cis form and trans form are no longer
distinguished due to addition of such a protective group (hereinafter, the term "vitamin
D structure" refers to one which is not limited to either a cis form or a trans form unlessotherwise specified).
f. The Corrected Description does not specially state the effect of the Corrected
Invention (see Article 36, paragraph (4) of the Patent Act and Article 24-2 of theOrdinance for Enforcement of the Patent Act). However, as mentioned above, theproblem to be solved of the Corrected Invention exists in the provision of a novel
process for preparing vitamin D or steroid derivatives having a Maxacalcitol Side Chain,
which had not been disclosed in prior art. Taking this into account, the effect of theCorrected Invention is recognized as being capable of preparing vitamin D or steroid
derivatives, such as maxacalcitol, which have a Maxacalcitol Side Chain by a novel
process which had not been disclosed in prior art.
(B) As mentioned above, the Corrected Invention makes it possible to prepare its
objective substance through a new preparation route that was not available in prior art,
and its degree of contribution to prior art is large. Then, out of the manufacturing
processes for maxacalcitol that were publicly known as of the Priority Date, the firstmanufacturing process for maxacalcitol described in Exhibit Ko 1 Publication had
disadvantages, such as cumbersome operation, low yield of the objective substance, anddifficulty in separation and purification. The manufacturing process mentioned in(A)c.[i] above, which is stated in the Corrected Description, was invented as an
improvement of said process (Exhibit Otsu 35). However, the process described in [i] isalso unfavorable for mass synthesis. Therefore, as of the Priority Date, further
improvements were considered, and new processes for industrially manufacturing
maxacalcitol were sought. The Corrected Invention made it possible for the appellee,
who held a substance patent for maxacalcitol, to industrially manufacture maxacalcitol

59for the first time (Exhibit Otsu 14; entire import of argument).
(C) On the other hand, the appellants allege that a process for introducing a
Maxacalcitol Side Chain through one step by using a starting material having atrans-form vitamin D structure is also publicly known based on the process described in
Publication of Japanese Translation of PCT International Application No. 1992-504573(Exhibit Otsu 4 Document) as prior art as of the Priority Date. The appellants also allege
that there is also a publicly known document (paper published in 1991 which is titled"22-okisabitamin D ruientai no gōsei oyobi seibutsugakuteki kassei" (Synthesis andbiological activity of 22-oxavitamin D analog); Exhibit Otsu 50) which indicates, prior
to the Priority Date, that it was possible to introduce a Maxacalcitol Side Chain throughone step. However, the invention described in Exhibit Otsu 4 Document is a process for
preparing a novel vitamin D derivative whose number of carbons of the side chain
differs from that of a Maxacalcitol Side Chain. In addition, Exhibit Otsu 4 Document
cannot be recognized as specifically disclosing a process for preparing a vitamin D
derivative having a Maxacalcitol Side Chain through one step even in consideration ofother statements therein. Moreover, regarding the "details of synthesis of an alcoholcompound to o-alkylation," it is stated in the publicly known document pointed out by
the appellants (Exhibit Otsu 50) that "see Reference Document 5 [note in this judgment:
page 45 of International Publication No. 1990/09991]." The only process for thesynthesis of a Maxacalcitol Side Chain that is specifically disclosed in International
Publication No. 1990/09991 (Exhibit Otsu 3-1) is a process for forming a Maxacalcitol
Side Chain by first reacting the alcohol compound at the 20-position with prenyl
bromide to introduce a side chain (which is not a Maxacalcitol Side Chain) by an etherbond and then having it react with mercury acetate (Preparation Examples 11 and 12 of
Exhibit Otsu 3-1). Therefore, it is reasonable to understand that the one referred to in
the aforementioned publicly known document (Exhibit Ko 50) is also said process.
Consequently, there is no reason for the appellants' allegation, and the statement of prior
art in the Corrected Description is not recognized as being objectively insufficient.
D. Essential part of the Corrected Invention
In light of the problem to be solved and means for solving the problem of theCorrected Invention and its effect as mentioned above, the essential part of theCorrected Invention (the characteristic part which constitutes a unique technical ideathat is not seen in prior art in the statements in the scope of claims) is recognized asexisting in finding that a side chain having an epoxy group by an ether bond can be
introduced through one step by having an alcohol compound at the 20-position of avitamin D structure or steroid ring structure react with an epoxy hydrocarbon compound60

of Constituent Feature [B-2] which has an eliminating group at its end, and in making it
possible to introduce a Maxacalcitol Side Chain into an alcohol compound at the
20-position of a vitamin D structure or steroid ring structure through a new route of firstgoing through an intermediate that is a vitamin D structure or steroid ring structure into
which a side chain having an epoxy group by an ether bond is introduced through such
one step and then opening the ring of the epoxy group of the side chain.
On the other hand, the fact remains that an intermediate that is obtained byintroducing a side chain having an epoxy group by an ether bond into the starting
material is synthesized by reacting the starting material with an epoxy hydrocarbon
compound and that a Maxacalcitol Side Chain can be introduced thereafter by opening
the ring of the epoxy group of the side chain, irrespective of whether the carbon
skeleton (Z) of the alcohol compound at the 20-position, which is the starting material,
has a cis-form or trans-form vitamin D structure. The same also applies to the cases
where the carbon skeleton (Z) of the intermediate is either a cis-form or trans-form
vitamin D structure. Therefore, the fact that the vitamin D structure of the carbon
skeleton (Z) of the starting material or the intermediate is a cis form cannot be
considered to be a characteristic part, which constitutes a unique technical idea that is
not seen in prior art in the statements in the scope of claims of the Corrected Invention,and it is thus not included in the essential part of the Corrected Invention.
E. Fulfillment of the First Requirement of the Appellant's Process
The Appellant's Process is a process for introducing a Maxacalcitol Side Chain into
the alcohol compound at the 20-position of a vitamin D structure by reacting the alcoholcompound at the 20-position of a vitamin D structure (Starting Material A) with thesame compound (Reagent B) as the epoxy hydrocarbon compound of Constituent
Feature [B-2] which has an eliminating group at its end, thereby going through anintermediate (Intermediate C) that is a vitamin D structure wherein a side chain having
an epoxy group is introduced by an ether bond into the starting material, and thenopening the ring of the epoxy group of the side chain thereafter. Therefore, it isconsidered to have the characteristic part which constitutes a unique technical idea thatis not seen in prior art in the statements in the scope of claims of the Corrected
Invention.
On the other hand, in the Appellant's Process, the point that a vitamin D structurethat corresponds to "Z" of the starting material and the intermediate is not a cis form but
a trans form, which is a difference from the Corrected Invention, is not the essential partof the Corrected Invention, as mentioned in D. above.
Therefore, the Appellant's Process is recognized as fulfilling the First Requirement61

of the doctrine of equivalents.
F. Regarding the appellants' allegation(A) The appellants allege as follows: The essence of the Corrected Invention exists insolving the problem (oxidation resistance) in the case of using a cis-form starting
material while enjoying the advantage of reduction of the number of steps by choosing a
cis-form starting material and finding an order of introduction of an ether bond and an
epoxy group that is suitable for said starting material (which does not include anoxidation step) because the conventional process described in Exhibit Ko 46 Publication
includes an oxidation step and thus had a problem of not being capable of efficiently
introducing a side chain in the case of using a cis-form starting material with low
oxidation resistance; therefore, the point that the starting material has a cis-form vitamin
D structure is an indispensable essential element; on the other hand, if the starting
material has a trans-form vitamin D structure, there is no problem of low oxidation
resistance, and it is not possible to enjoy the advantage of reduction of the number ofsteps because an isomerization step is required.
However, as mentioned above, the essential part of a patented invention should befound by determining the characteristic part which constitutes a unique technical ideathat is not seen in prior art in the statements in the scope of claims of the patented
invention. As mentioned above, the problem to be solved of the Corrected Invention isto provide a novel process for introducing a Maxacalcitol Side Chain which is disclosed
neither in the art described in Exhibit Otsu 46 Publication nor in other prior arts
described in the Corrected Description, and the Corrected Invention provides a means
for solving the problem. Then, the process described in Exhibit Otsu 46 Publication has
problems, such as oxidation resistance, in using a cis-form starting material, and even if
such problems do not occur in the case of the Corrected Invention, there is no reason forunderstanding the problem solved by the Corrected Invention as being limited as suchaccording to the findings in C. and D. above. Therefore, using a compound with low
oxidation resistance as the starting material cannot be recognized as the essential part of
the Corrected Invention.
Moreover, it is certainly true that using a cis-form starting material has theadvantage of not requiring an isomerization step. However, Reaction Scheme C in the
Corrected Description describes a route of conversion from a steroid compound to avitamin D compound in any of the stages of the starting material, intermediate, andobjective substance. As of the Priority Date, the synthesis of a vitamin D compoundfrom a steroid compound could have been carried out by a conventional process. The
Corrected Invention includes not only a compound having a cis-form vitamin D

62

structure but also a compound having a steroid ring structure as the starting material. In
the case of choosing a steroid ring structure as "Z," a process which comprises the stepof subjecting the steroid ring structure to ultraviolet irradiation and thermal
isomerization under the conditions for converting it into a vitamin D structure and thestep of recovering the compound thus prepared as the objective substance is also
described as one of the embodiments of the Corrected Invention (B.(B)e. above). That is,in the Corrected Invention, the difference in the total number of steps that depends onthe existence or absence of a conversion step cannot be considered to be the essential
part of the Corrected Invention, taking into account that the total number of steps,
including a conversion step, can originally vary depending on whether "Z" of thestarting material is a steroid ring structure or a vitamin D structure.
In this regard, the appellants allege that the essential part of the Corrected Invention
naturally differs in the case of using a compound having a steroid ring structure as thestarting material compared to the case of using a compound having a vitamin D
structure as the starting material. However, even if multiple options are stated in thescope of claims, the essential part of a patented invention should be found based on theentire statements in the scope of claims in light of the technical significance ofpermission of such options. Therefore, the appellants' allegation is unacceptable.
(B) Moreover, the appellants also allege as follows: The effect of the Corrected
Invention exists in the reduction of the number of steps required to introduce a
Maxacalcitol Side Chain compared to prior art; however, there has been prior art
whereby a Maxacalcitol Side Chain can be introduced through one step in the case ofusing a trans-form starting material; therefore, the Appellant's Process cannot be
considered to be identical with the Corrected Invention in the essential part. However,as mentioned in C.(C) above, it cannot be recognized that a process whereby a vitamin
D derivative having a Maxacalcitol Side Chain can be prepared through one step byusing a trans-form starting material has been publicly known. In addition, the functionand effect of the Corrected Invention and the fact that the Appellant's Process produces
the same function and effect are as mentioned later in (4)C. Therefore, there is no reason
for the appellants' allegation.
(C) The appellants allege as follows: In the technical field of processes for preparing
compounds, the organic linkage of all the steps itself is a technical idea for solving aproblem, and a manufacturing process using a cis-form starting material and amanufacturing process using a trans-form starting material are understood as different
processes by persons ordinarily skilled in the art; therefore, it is erroneous to take up
only a part of a manufacturing process and consider it as the essential part thereof in63

disregard of differences in the starting material and the intermediate, which areimportant constituent elements of the manufacturing process, and differences in stability,
easiness of purification, and the total number of required steps between a cis form and atrans form.
However, as mentioned above, the essential part of a patented invention should befound by determining the characteristic part which constitutes a unique technical ideathat is not seen in prior art in the statements in the scope of claims of the patented
invention. The entire organic linkage of all steps cannot necessarily be considered toform the essential part even in relation to a process for preparing a compound.
Therefore, existence of slight differences in the starting material and the intermediatethat do not affect a reaction required to introduce a side chain does not immediately
mean the existence of differences in the essential part.
In addition, a manufacturing process using cis-form starting material andintermediate and one using trans-form starting material and intermediate are generally
understood as different manufacturing processes. Moreover, even if these processes
differ in stability, easiness of purification, and the total number of steps, the essential
part of the Corrected Invention exists in that it made it possible to introduce a
Maxacalcitol Side Chain into the alcohol compound at the 20-position of a vitamin D
structure or a steroid ring structure by a novel manufacturing process that had not been
disclosed in prior art as found in D. above, and said novel process for introducing a side
chain does not differ depending on whether the starting material or the intermediate is a
cis form or a trans form, and differences in stability, easiness of purification, and thenumber of steps between a cis form and a trans form are also not related to the essential
part of the Corrected Invention. The existence of a difference in the function and effectother than the characteristic part which constitutes a unique technical idea that is notseen in prior art in the statements in the scope of claims of the Corrected Invention does
not serve as a reason for denying that the Appellant's Process commonly has theessential part of the Corrected Invention.
Therefore, there is no reason for the appellants' allegation.
(4) Regarding the Second Requirement of the doctrine of equivalents (replaceability)
A. As mentioned above, the Appellant's Process and the Corrected Invention differ inthat the carbon skeletons of Starting Material A and Intermediate C in the Appellant's
Process are trans-form vitamin D structures while the carbon skeletons of the alcoholcompound at the 20-position of a vitamin D structure (Constituent Feature [B-1]), whichis the starting material of the Corrected Invention (in the Corrected Invention, thecarbon skeletons that correspond to Z of the starting material and the intermediate are64cis-form vitamin D structures, and the protected hydroxyl group is bonded to the
1-position and the 3-position of the vitamin D structure as a substituent in the samemanner as the starting material of the Appellant's Process), and the vitamin D structure
into which a side chain having an epoxy group by an ether bond is introduced(Constituent Feature [B-3]), which is the intermediate of the Corrected Invention, arecis-form vitamin D structures. Then, it is considered whether it is possible to achieve
the purpose of the Corrected Invention and to produce the same function and effect as
those of the Corrected Invention even if the starting material and the intermediate of theCorrected Invention are replaced with those of the Appellant's Process.
B. As mentioned in (3)C.(A)d. above, the problem to be solved of the Corrected
Invention is to provide a novel manufacturing process which has not been disclosed inprior art as a process for preparing a vitamin D derivative having a Maxacalcitol Side
Chain. The means for solving the problem is to prepare maxacalcitol by a novel process
which comprises the step of reacting the alcohol compound at the 20-position of avitamin D structure (compound of Constituent Feature [B-1]), in the presence of a base,with the epoxy hydrocarbon compound of Constituent Feature [B-2] which has aneliminating group at its end to synthesize an epoxide compound (intermediate ofConstituent Feature [B-3]), which is a vitamin D structure into which a side chain
having an epoxy group is introduced by an ether bond and the step of subsequently
opening the ring of the epoxy group of said side chain. In that case, the function andeffect of the Corrected Invention in relation to the Second Requirement is recognized as
being capable of preparing maxacalcitol by a process which comprises the step ofreacting the alcohol compound at the 20-position of a vitamin D structure with an epoxyhydrocarbon compound having an eliminating group at its end and the step of going
through an intermediate that is a vitamin D structure into which a side chain having an
epoxy group is introduced by an ether bond through one step.
C. Then, as mentioned above, the Appellant's Process is to prepare the same
maxacalcitol as that of the Corrected Invention by reacting Starting Material A (alcoholcompound at the 20-position of a trans-form vitamin D structure) with Reagent B(epoxy hydrocarbon compound of Constituent Feature [B-2] of the Corrected Invention)
to produce Intermediate C which is an epoxide compound, which is a trans-form
vitamin D structure into which a side chain having an epoxy group is introduced by an
ether bond, then opening the ring of the epoxy group of said side chain to produce
Substance D having a Maxacalcitol Side Chain, and finally subjecting Substance D tolight illumination to convert its carbon skeleton into a cis-form vitamin D structure.
In the aforementioned Starting Material A and Intermediate C in the Appellant's

65Process, the carbon skeleton that corresponds to Z in the Corrected Invention is atrans-form vitamin D structure, and the Appellant's Process differs from the Corrected
Invention in that the carbon skeleton of Z of the starting material (Constituent Feature[B-1]) and the intermediate (Constituent Feature [B-3]) of the Corrected Invention is a
cis-form vitamin D structure. However, the starting materials and intermediates in both
the Appellant's Process and the Corrected Invention have the same function and effectof being capable of preparing maxacalcitol by a process of going through anintermediate that is a vitamin D structure into which a side chain having an epoxy groupis introduced by an ether bond through one step by having an alcohol compound at the
20-position of a vitamin D structure react with the same epoxy hydrocarbon compound.
It is recognized that the same purpose as that of the Corrected Invention can be achieved
and the same function and effect are produced even if the aforementioned starting
material and intermediate having a cis-form vitamin D structure in the Corrected
Invention are replaced with the aforementioned starting material and intermediate
having a trans-form vitamin D structure in the Appellant's Process.
D. The appellants allege as follows: The only effect stated in the Corrected Description
is reduction of the number of steps, and the function and effect of the Corrected
Invention exist in the reduction of the number of steps for introducing a Maxacalcitol
Side Chain in the case of using a cis-form starting material compared to prior art; inaddition, the efficiency of the reduction of the number of steps should be determinedbased on the total number of manufacturing steps, and processes do not have the samefunction and effect if the total number of steps differ between them. However, theaforementioned appellants' allegation is unacceptable for the following reasons.
In Article 36, paragraph (4) of the Patent Act prior to amendment by Act No. 116 of1994, the "purpose, structure, and effect of the invention" were provided for as thematters that must be stated in the detailed explanation of the invention in the description.
However, through said amendment, the "problem to be solved and means for solving the
problem," etc. are provided for as the matters that must be stated in said paragraph after
the amendment and in Article 24-2 of the Ordinance for Enforcement of the Patent Act.
The effect of the invention is no longer provided for as a matter that must be stated in
the detailed explanation of the invention in the description. In the current practice, there
are many descriptions that do not include any statement of the "effect of the invention"
in relation to a patented invention pertaining to an international application, etc. (this isa noticeable fact in this court). The absence of the statement of the "effect of theinvention" in the Corrected Description also conforms to this amendment. Then, it is notreasonable to presumptively recognize the function and effect of a patented invention,

66

for which the "effect of the invention" is not stated in the description, in a limited
manner based only on comparison with some of prior arts.
Among prior arts, the invention described in Exhibit Otsu 46 Publication is stated asfollows in the Corrected Description: "The aforementioned processes require more than
one step for introducing an ether bond and an epoxy group into a side chain of a steroid
group and therefore, result in low yield of the desired compound" ((3)B.(A) above).
However, said statement only refers to one of the multiple inventions cited as prior art
in the Corrected Description. In addition, it is a statement concerning only steps for
introducing a specific side chain, specifically, steps for introducing an epoxy group by
an ether bond, and is not intended to refer to the number of steps in the entire process,including these steps. Originally, the process described in Exhibit Otsu 46 Publication is
not a manufacturing process wherein a Maxacalcitol Side Chain is introduced.
Therefore, said statement cannot serve as a reason for saying that the reduction of thenumber of steps for introducing a Maxacalcitol Side Chain in the case of using a
cis-form starting material compared to prior art is the function and effect of theCorrected Invention. Moreover, as mentioned in (3)F.(A) above, the Corrected
Invention also includes the step of converting a steroid ring structure to a vitamin D
structure, and a difference (fewer steps) in the total number of steps, including theconversion step, is not particularly recognized as a difference from prior art. Taking this
into account, the function and effect of the Corrected Invention cannot be found to be
the reduction of the total number of steps for preparing the objective substance, such as
maxacalcitol, compared to prior art.
E. Therefore, the Appellant's Process is recognized as fulfilling the Second Requirementof the doctrine of equivalents.
(5) Regarding the Third Requirement (easiness of replacement) of the doctrine ofequivalents
According to evidence (described in the text), the following facts are recognized: [i]The knowledge that a trans-form vitamin D structure can be easily converted into a
cis-form vitamin D structure by light illumination was well-known art as of the Priority
Date, and it was a widely-known process to obtain a cis-form vitamin D derivative byusing a compound having a trans-form vitamin D structure as the starting material in
preparing a desired vitamin D derivative and converting the trans-form vitamin D
structure into a cis-form vitamin D structure by light illumination after introducing aside chain as appropriate (Exhibit Ko 14 and Exhibits Otsu 1, 2, and 33); [ii] It was also
known that a trans-form vitamin D structure that corresponds to Starting Material A of
the Appellant's Process is used for the synthesis of maxacalcitol (Exhibit Otsu 4-2); [iii]67Even in the case of using a compound having a cis-form vitamin D structure as thestarting material, it was generally accepted to adopt processes wherein the compound isconverted into a trans form at the time of introducing a substituent, etc. or removing aprotective group in the course of preparation and is reconverted into a cis form (Exhibit
Otsu 1).
Moreover, it is generally known that the steric structure near the reaction point
significantly affects the progress of a chemical reaction. The hydroxyl group with which
the alcohol compound at the 20-position of a vitamin D structure, which is the starting
material, reacts upon the introduction of a Maxacalcitol Side Chain is far from theposition of the double bond (5-position) of the vitamin D structure, which differs
between a trans form and a cis form. The steric structure near the reaction point does notdiffer depending on whether the starting material has a trans-form vitamin D structure
or a cis-form vitamin D structure. Taking this into account, it is natural for a person
ordinarily skilled in the art not to consider that the reaction in the course of introductionof a Maxacalcitol Side Chain in the Corrected Invention does not differ depending on adifference between a trans form and a cis form in the position of the double bond.
In that case, it is recognized that a person ordinarily skilled in the art could have
easily conceived of the Appellant's Process, which uses a trans-form vitamin D structure
as "Z" of the starting material of the Corrected Invention in place of a cis-form vitamin
D structure for preparing maxacalcitol that is contained in the objective substance of theCorrected Invention and comprises the step of reacting this Starting Material A with
Reagent B that is the same reagent as that of the Corrected Invention to produce
Intermediate C that has no difference from the intermediate of the Corrected Invention
other than the point that it is a trans form, the step of opening the ring of the epoxy
group of the side chain of intermediate C to obtain Substance D that is a trans form
having a Maxacalcitol Side Chain, and the step of finally subjecting Substance D tolight illumination to convert it into a cis form and removing the protective group of thehydroxyl group to prepare maxacalcitol that is the same as the objective substance of theCorrected Invention, based on the Corrected Invention at the time when the Appellant's
Process was carried out (when the Patent Right was infringed).
Therefore, the Appellant's Process is recognized as fulfilling the Third Requirementof the doctrine of equivalents.
(6) Regarding the Fourth Requirement (whether the subject process can be easily
presumptively conceived of) of the doctrine of equivalents
The appellants allege that the Appellant's Process could have been easily
presumptively conceived of by a person ordinarily skilled in the art as of the Priority

68Date based on Exhibit Otsu 4 Document. However, said allegation of the appellants is
unacceptable as held in No. 4, 4.(1) to (6) in "Facts and reasons" in the judgment inprior instance. The relevant part is cited.
Therefore, the Appellant's Process is not recognized as having been easily
presumptively conceived of by a person ordinarily skilled in the art in relation to the
Fourth Requirement of the doctrine of equivalents.
(7) Regarding the Fifth Requirement (special circumstances) of the doctrine ofequivalents
A. Regarding the determination standard for the Fifth Requirement
The substantive value of a patented invention extends to the art which a person
ordinarily skilled in the art can easily conceive of as one that is substantially identicalwith the structure stated in the scope of claims based on said structure, and third parties
should foresee this. Therefore, if the subject product, etc. is identical with a patented
invention in the essential part, purpose, and function and effect, and is one that a person
ordinarily skilled in the art can easily conceive of based on the patented invention, thesubject product, etc. can be in principle considered to be equivalent to the patented
invention. However, concerning art which the patentee had once acknowledged not tofall under the technical scope of the patented invention or art in relation to which he/she
had behaved as if he/she had objectively acknowledged so, e.g. where the applicant
intentionally excluded the art from the scope of claims in the patent application
procedures, the patentee is not entitled to claim otherwise afterwards, since this isagainst the doctrine of estoppel. Therefore, if there are such special circumstances, theapplication of the doctrine of equivalents is exceptionally denied (see theaforementioned Supreme Court Judgment on the "Ball spline bearing" Case).
(A) In this regard, even if there is another structure that is outside the scope of claims,
which a person ordinarily skilled in the art can easily conceive of as of the filing date as
one that is substantially identical with the structure stated in the scope of claims and theapplicant could thus have also easily conceived of said another structure as of the filing
date, this fact alone cannot serve as a reason for alleging that the applicant's failure tostate said another structure in the scope of claims falls under the "special circumstances"in the Fifth Requirement of the doctrine of equivalents.
This is because of the following reasons. [i] As mentioned above, the substantive
value of a patented invention extends to the art that a person ordinarily skilled in the art
can easily conceive of as one that is substantially identical with the structure stated in
the scope of claims based on said structure even if it is a structure other than the
structure stated in the scope of claims. This principle does not change at all in relation to69

any art that a person ordinarily skilled in the art can easily conceive of as of the filingdate. If it is not at all permitted to allege the doctrine of equivalents only for the reason
that a structure could have been easily conceived of by a person ordinarily skilled in theart as of the filing date, the scope to which the substantial value of a patented invention
extends will differ from the aforementioned scope. [ii] In addition, taking into accountthat an applicant should first disclose his/her invention to the public by stating it in thedescription and then clearly specify the scope of the exclusive right in the scope ofclaims, the applicant should state the scope of claims in just proportion within the scopeof the invention disclosed in the description while fulfilling the requirements, such as
the support requirements under Article 36, paragraph (5) of the Patent Act andparagraph (6), item (i) of said Article and the clarity requirements under item (ii) of said
paragraph. However, in some cases, it is considered to be harsh to require the applicant
to prepare the scope of claims that contains all the expected infringements and thedescription supporting such scope of claims within a limited period of time, taking into
account the fact that, under the first-to-file system, applicants are generally required toprepare the scope of claims and the description and file applications within a limited
period of time. On the other hand, in many cases, a third party who has received thedisclosure of an invention as described in the description pertaining to a patentapplication can easily conceive of one which has the essential part of the patented
invention but part of which is not included in the literal interpretation of the scope ofclaims, based on the statements in the scope of claims and the description, etc., during
the duration of the patent. The doctrine of equivalents is applicable because if any third
party can easily escape from the exercise of rights by the patentee, including an
injunction, through replacement of the non-essential part of the patented invention, thiswill diminish incentives for invention in society in general, which not only goes against
the purpose of the Patent Act, that is, contributing to the development of industry
through protection and encouragement of inventions, but also goes against social justiceand results in running counter to the principle of fairness. In light of the aforementioned
situation, etc., even if a person ordinarily skilled in the art could have easily conceivedof another structure that is outside the scope of claims as of the filing date, it is notreasonable to exclude said another structure from the application of the doctrine ofequivalents only for the reason of such fact without exception.
(B) However, even in such a case, if the applicant is objectively and externallyrecognized as having recognized another structure that is outside the scope of claims as
a replacement for a different part in the structure stated in the scope of claims as of thefiling date (for example, where the applicant can be considered to have stated the70invention based on said another structure in the description or where the applicant statedthe invention based on another structure that is outside the scope of claims in a paper,
etc. which he/she published as of the filing date), the applicant's failure to state said
another structure in the scope of claims is considered to fall under the "special
circumstances" in the Fifth Requirement.
The reason therefor is as follows. In the aforementioned cases, it can be understoodthat the patentee intentionally excluded said another structure from the scope of claims
when stating the scope of claims, that is, the patentee acknowledged that said anotherstructure does not fall under the technical scope of the patented invention or behaved asif he/she had objectively acknowledged so, and the trust of a third party who
understands as such should be protected. Therefore, the patentee is not permitted tosubsequently allege the application of the doctrine of equivalents in relation to thesubject product, etc. that is based on said another structure in contradiction to suchprotection in light of the doctrine of estoppel.
B. Regarding the appellants' allegations(A) The appellants allege as follows: For an invention in the chemical field, the scope ofclaims is generally specified by objective and clear expressions; therefore, thethird-party trust that the right will never expand from said scope naturally arises, and it
should be protected. However, as mentioned above, the right under the doctrine ofequivalents extends to the art which a person ordinarily skilled in the art can easily
conceive of as one that is substantially identical with the structure stated in the scope ofclaims based on said structure even if the art is outside the scope that is literally
specified in the scope of claims, and third parties should foresee this. It is not permitted
to allege the doctrine of equivalents in light of the doctrine of estoppel only where there
are the aforementioned special circumstances. The fact that the invention is one in thechemical field or the fact that the scope of claims is literally clear cannot serve as areason for denying the establishment of equivalence as such "special circumstances."
Therefore, there is no reason for the appellants' allegation.
(B) The appellants allege the circumstances as indicated in the appellants' allegation in
B.(A) to (G) in No. 3, 1.(4) above. Then, the appellants allege as follows: In stating thescope of claims, the applicant for the Corrected Invention decided the starting material,
being clearly and objectively conscious of not including a trans-form vitamin D
structure in the scope of claims, and thus intentionally chose to actively exclude atrans-form vitamin D structure from the scope of claims; therefore, in this case, there arethe "special circumstances, such as the fact that the products fall under those that were71

intentionally excluded from the scope of claims," as mentioned in the Supreme Court
Judgment on the "Ball spline bearing" Case; in addition, there is no circumstance where
the patentee should be specially protected, which is indicated as a ground for theapplication of the doctrine of equivalents in said judgment, specifically, the fact that "itis extremely difficult to foresee all kinds of infringements … and state the scope ofclaims in the description."
However, as mentioned below, the Corrected Description includes no statement thatcan be considered to state an invention using a compound having a trans-form vitamin
D structure as the starting material of the Corrected Invention (the parties agree that aninvention using a starting material having a trans-form vitamin D structure is notdisclosed in the Corrected Description). In addition, there is no other evidence that is
sufficient to objectively and externally recognize that the applicant recognized atrans-form vitamin D structure as a replacement for a cis-form vitamin D structure as
the starting material of the Corrected Invention as of the filing of the application for the
Patent. Therefore, it should be said that there is no reason for the appellants' allegation.
a. The appellants allege that the applicant was never erroneously ignorant of theexistence of a synthesis route using a starting material having a trans-form vitamin D
structure because the existence of two kinds of geometric isomers and a synthesis routeusing a starting material having a trans-form vitamin D structure were well-known.
However, even if the applicant of the Corrected Invention knew that a trans form
generally exists as a geometric isomer of a cis form and that there is a process for thesynthesis of a vitamin D derivative using a starting material having a trans-form vitamin
D structure, these facts alone cannot serve as a reason for saying that the applicant isobjectively and externally recognized as having recognized the use of a starting material
having a trans-form vitamin D structure as a replacement for the starting material of theCorrected Invention as of the filing date. Therefore, there is no reason for the appellants'
allegation.
b. The appellants allege as follows: The scope of claims of the Corrected Invention
describes a chemical bond by a wavy line, "〰H" (Constituent Feature [B-3]), thereby
clearly describing that the steric structure at the root of H includes the stereoisomers ofboth R-stereoisomer and S-stereoisomer; however, it describes only the cis-form
geometric isomer of a vitamin D structure; therefore, it clearly and intentionally sets a
limitation to exclude a trans form. However, RS-stereoisomerism (enantiomerism) andcis-trans stereoisomerism (geometric isomerism) differ in their properties. Even if there
is a statement that is based on the premise of distinction between R-stereoisomer andS-stereoisomer in the Corrected Description, it cannot be said that the applicant is72

objectively and externally recognized as having recognized a trans-form vitamin D
structure as a replacement for the starting material of the Corrected Invention. Therefore,
the applicant is not recognized as having intentionally limited the scope of claims.
Consequently, there is no reason for the appellants' allegation.
c. The appellants allege as follows: Two structural formulas, one expressing thestructure immediately after adding SO2 to a cis-form starting material and one
expressing the structure immediately after adding SO2 to a trans-form starting material,
are stated in the Corrected Description, and there is a statement on the assumption of atrans-form starting material in the Corrected Description; despite this fact, the applicant
limits the starting material to a cis form in the scope of claims; therefore, in this regard,
it is obvious that the applicant intentionally limited the starting material.
However, in Claim 13, "Z" of the Corrected Invention is clearly specified as one that"may optionally have one or more protected or unprotected substituents and/or one ormore protective groups." Both of the two structural formulas ((3)B.(B)b. above) in the
Corrected Description as pointed out by the appellants are nothing more than those thatindicate a vitamin D structure to which SO2 is added as a protective group as an
example of "Z" to which such protective group is added. These structural formulas do
not describe a compound before SO2 is added. Regarding a compound wherein SO2 isadded to a vitamin D structure, the double bond of the vitamin D structure is lost andthe rotational hindrance is eliminated, and the compound ceases to be a geometricisomer. Therefore, there is no line between a cis form and a trans form in relation to theaforementioned two structural formulas themselves. In that case, such statement of
examples of "Z" to which a protective group is added is not sufficient to objectively andexternally recognize that the applicant had recognized a trans-form vitamin D structure
as a replacement for the starting material of the Corrected Invention. Therefore, itcannot be said that the applicant intentionally limited the starting material in the scopeof claims. Consequently, there is no reason for the appellants' allegation.
d. The appellants allege as follows: In Column 41 in the Corrected Description, twointernational publications describing a trans-form vitamin D structure as the starting
material in addition to a cis-form vitamin D structure are described; however, inColumn 37 in the Corrected Description, the starting material is "particularly" limited toa cis form out of the two kinds of existing basic skeletons, and only a cis form is statedin the scope of claims; therefore, a trans-form vitamin D structure is intentionally
excluded in the Corrected Description.
In Column 41 in the Corrected Description, the following is stated as the examplesof publicly known compounds that can be used as a starting compound when preparing73

a compound that falls under the intermediate of the Corrected Invention:"9,10-seco-5,7,10(19)-pregnatriene-1α,3β,20β-triol optionally with the hydroxyl group
being protected as described in Publication of Unexamined Patent Application No.
1986-267550 (issued on November 27, 1986) and International Patent Publications
WO/1990/09991 (September 7, 1990) and WO/1990/09992 (September 7, 1990)"((3)B.(B)c.
above).
However,thestatement"9,10-seco-5,7,10(19)-pregnatriene-1α,3β,20β-triol" is a general notation that does not
limit the vitamin D structure to either cis form or trans form. The aforementioned
statement in Column 41 does not describe an invention using a starting material having
a trans-form vitamin D structure. Then, in each of the cited publications, a structural
formula of a cis-form vitamin D structure or that of a trans-form vitamin D structure is
described in the course of the manufacturing process pertaining to the invention
described in each publication. However, in the Corrected Description, these documents
are
cited
only
as
those
that
describedacompound,"9,10-seco-5,7,10(19)-pregnatriene-1α,3β,20β-triol."
In addition, Column 37 in the Corrected Description as pointed out by the appellants
specifies and describes the same content as that of the statements in the scope of claims,
and it does not clearly specify a trans-form vitamin D structure as "Z" of the starting
material, etc.
Then, the Corrected Description does not refer to a trans-form vitamin D structure atall. For example, it does not describe the step of converting a trans form to a cis form.
There is no statement concerning an invention pertaining to a manufacturing processusing a trans-form starting material in the Corrected Description.
In that case, it cannot be considered, based on each of the aforementioned
statements in the Corrected Description, that an invention using a compound having atrans-form vitamin D structure as the starting material of the Corrected Invention isstated in the Corrected Description. In addition, said statements are not sufficient toobjectively and externally recognize that the applicant recognized a trans-form vitamin
D structure as a replacement for the starting material of the Corrected Invention as of
the filing date. Therefore, it is not recognized that a trans-form vitamin D structure wasintentionally excluded from the scope of claims. Consequently, there is no reason for
the appellants' allegation.
e. The appellants allege as follows: Although working examples using a starting
material having a steroid ring structure are only stated in the Corrected Description, theinvention is generalized and enlarged in the scope of claims to include the cases where astarting material has a cis-form vitamin D structure; if a third party sees such74

description, he/she recognizes that structures that are not stated in the scope of claims
were excluded. However, the statements in the scope of claims do not need to be
identical with the scope of the invention stated in the working examples, although theyneed to be supported by the description. It is general practice that the invention whose
content is more generalized than the content indicated in working examples is stated in
the scope of claims. Such fact alone does not serve as a ground for objectively andexternally recognizing that the applicant has recognized one other than the starting
material stated in the scope of claims as a replacement for said starting material.
Therefore, it cannot be said that there are special circumstances, such as the fact that theapplicant intentionally limited the scope of claims. Consequently, there is no reason for
the appellants' allegation.
f. The appellants allege that the applicant had no difficulty in including a trans-form
vitamin D structure as Z of the starting material. However, even if the applicant caneasily conceive of another structure that is outside the scope of claims as one that is
substantially identical with the structure stated in the scope of claims as of the filing
date, this fact alone cannot serve as a reason for saying that there are special
circumstances, such as the fact that the applicant intentionally excluded said anotherstructure, as mentioned in A.(A) above. Therefore, there is no reason for the appellants'
allegation.
g. The appellants allege as follows: It is considered that the applicant limited the starting
material to a cis form because it was highly likely to be unable to receive an examiner's
decision to grant a patent based on the allegation of the effect of reducing the number ofsteps if it included a starting material having a trans-form vitamin D structure in thesubject of the invention. However, as mentioned in (4)D. above, the function and effectof the Corrected Invention are not recognized as existing in the reduction of the numberof steps, and rather, the essential part of the Corrected Invention is recognized as
mentioned in (3)D. above. The use of a cis-form starting material is not at all related tothe essential part. Taking this into account, it cannot be recognized that the appellee
intentionally excluded trans-form starting materials from the starting material of theCorrected Invention in consideration of the function and effect alleged by the appellants.
Therefore, there is no reason for the appellants' allegation.
h. According to the above, in this case, the applicant cannot be regarded as stating an
invention using a starting material having a trans-form vitamin D structure in the
Corrected Description, and it is not objectively and externally recognized that theapplicant recognized a trans-form vitamin D structure as a replacement for the starting
material of the Corrected Invention as of the filing date. Therefore, the applicant's

75

failure to state a structure wherein "Z" is a trans-form vitamin D structure in the scopeof claims cannot be considered to fall under the "special circumstances" in the Fifth
Requirement.
(C) The appellants allege that the statements in the document which the appellee sent
prior to the commercialization of the Appellants' Products fall under an indication of
intentional limitation of the scope of claims by the patentee.
However, in said document (written opinion prepared by the counsel attorney for theappellee), the appellee also made an allegation of infringement under the doctrine ofequivalents to the effect that the Appellant's Process is equivalent to the Corrected
Invention in the case of choosing a cis-form vitamin D structure as "Z" of the starting
material and intermediate stated in the scope of claims. Therefore, even if the appellee
also selectively made another allegation, it cannot be regarded as having intentionallylimited the scope of claims by making said another allegation (incidentally, as
mentioned above, in this lawsuit, the parties agree that the Appellant's Process does notconstitute the literal infringement of the Invention prior to the Correction in the case ofusing a starting material having a CD ring structure). Therefore, there is no reason for
the appellants' allegation.
(D) Even based on the other allegations of the appellants, it is not recognized that there
are the special circumstances of the Fifth Requirement of the doctrine of equivalents.
Therefore, there are no special circumstances of the Fifth Requirement of thedoctrine of equivalents in the Appellant's Process.
(8) Brief summary
On these bases, the Appellant's Process is equivalent to the Corrected Invention andis recognized as falling under the technical scope thereof.
2. Regarding the existence or absence of grounds for invalidation of the Corrected
Invention(1) Regarding the lack of an inventive step by citing Exhibit Otsu 14 Document as theprimarily cited document (Ground for Invalidation A)
A. Content described in Exhibit Otsu 14 Document
Exhibit Otsu 14 Document is a paper written by Noboru Kubodera, who is one of
the inventors of the Corrected Invention, which is titled "Active Vitamin D Analogs Important and Various Roles by Medicinal Chemists during the Course of Developmentof Promising Candidates as Useful Medicines." The paper was published in "Journal of
Synthetic Organic Chemistry, Japan, Vol. 54, No. 2" on February 1, 1996 prior to thePriority Date (September 3, 1996). There are the following statements in the paper.
(A) "1. Introduction76

1α,25-dihydroxy-22-oxavitamin D3 (2) (22-oxacalcitroiol; hereinafter abbreviated to"OCT" [note in this judgment: maxacalcitol]), which was produced for the purpose of
separating
variousphysiologicalactivitiesofactivatedvitaminD,
1α,25-dihydroxyvitamin D3 (1) (calcitriol; hereinafter abbreviated to "1,25(OH)2D3"),
by means of structure modification has strong differentiation-inducing activity andgrowth-inhibiting activity on tumor cells, such as leukemia cells, while it ischaracterized by having weak blood calcium level increasing activity. It has been
considered to be one of the derivatives which is most advanced in the separation of theactivities of 1,25(OH)2D3 up to the present date. …
Incidentally, the work of researchers who are working in a synthesis laboratory of apharmaceutical company tends to be focused on research to discover early active
substances. However, in fact, their work not only includes such research but also
various other roles, such as consideration of a manufacturing process for establishing a
mass synthesis process and synthesis of isotope labeled substances, anticipatedmetabolites, and other related substances, which can be considered to be "thanklessroles," during the course of producing medicines. … The authors would like to mention
various roles which medicinal chemists play during the development of promising
candidates as useful medicines, while focusing attention on some items in synthesis
which they have engaged in for the last few years during the course of drug
development, that is, the development research of OCT." (line 1 in the left column ofpage 139 to line 12 in the right column thereof)(B) "3. Consideration of a mass synthesis process—problems in conventional processes
and improvements thereto
Then, by the time when candidate specimens are narrowed down and the directionof development is decided, supply of a large number of specimens becomes necessary.
…
The process whereby OCT was synthesized at first is indicated in Figure 5 [note inthis judgment: same as the process described in the aforementioned Exhibit Ko 1
Publication]. The weak point of this process is that by-product (9) is produced in thealkylation of alcohol (8). 9 is separated as an unreacted substance in the next step, theWacker oxidation, but it was a problematic loss. This production of by-product (9)arises from low reactivity caused by the steric hindrance of the hydroxyl group of 8. As
a result of considering the alkylation reaction of 8 through dozens of series of reactions,
it was revealed that the improved process that goes through the Michael Addition
reaction-methylation reaction is efficient, as indicated in Figure 6. This process is
adopted at present. However, even in this methylation reaction, CeCl3·7H2O is used by77

subjecting it to dehydration and anhydration by an oven at 250°C. Therefore, thereaction is disadvantageous for mass synthesis though there is no problem at thelaboratory level. Thus, further improvement is being considered." (fifth line from thebottom in the right column of page 140 to line 8 in the left column of page 142)(C) "4. Synthesis of related compounds
4.1 Synthesis of anticipated metabolites
In deciding the structure of a metabolite, an important and also easier option is to
directly compare those that were actually extracted and isolated from biological samples
and those that were chemically synthesized. Assuming the part subjected to metabolism
by looking at the structure of a medicine and synthesizing and providing an anticipatedmetabolite is of great help for researchers engaging in metabolic experiments.
In the case of 1,25(OH)2D3, it is well-known that the 23, 24, and 26-positions arehydroxylated and are finally metabolized to calcitroic acid. Then, in the case of OCT,
the synthesis of 24-hydroxylated OCT (10) and (11), 26-hydroxylated OCT (12) and(13) [note in this judgment: a Maxacalcitol Side Chain of which the 26 position ishydroxylated], and pentanor OCT (15) deriving from hemiacetal (14), which is
produced by the hydroxylation of the 23-position, was also considered as indicated in
Figure 7." (line 17 in the left column of page 142 to line 12 of the right column thereof)[Figure 7](D) "Furthermore, regarding 26-hydroxylated OCT (12) and (13), as indicated in Figure
9, epoxide (18) and (19) were obtained by using the Katsuki-Sharpless reaction in the
key step, and each was led to 26-hydrozylated OCT of which the 25-position is R
Coordination (12) and S Coordination (13), respectively. … (Figure 9)" (line 16 in the78right column of page 142 to line 2 in the left column of page 143)
[Figure 9]

B. Content of Exhibit Otsu 14 Invention
According to A. above, Figure 9 of Exhibit Otsu 14 Document is recognized as
disclosing the following process (Exhibit Otsu 14 Invention).
"A process for obtaining the anticipated metabolites of maxacalcitol indicated as (12)and (13) in Figure 9 (see Figure 7), which comprises the step of reacting the following
20(S)-alcohol (8):(in the formula, TBS is t-butyldimethylsilyl that is a protective group)with 4-bromo-2-methyl-tetrahydropyranyloxy-2-butene(in the formula, THP is tetrahydropyran)to produce the following steroid compound [the same as the figure at the top center of
Figure 9]:79

(in the formula, R1=THP and R2=H),
the step of subsequently producing the following epoxide compounds (18) and (19) byusing the Katsuki-Sharpless reaction:

Compound 18

Compound 19

and the step of reducing these epoxide compounds with DIBAH (diisobutylaluminum
hydride) and subsequently subjecting them to light illumination and thermal
isomerization."
C. Common features and differences between the Corrected Invention and Exhibit Otsu
14 Invention(A) The Corrected Invention and Exhibit Otsu 14 Invention are identical with each otherin the following points.
"A process for preparing a compound having the following structure:(in the formula, W is hydrogen, X is methyl; Y is O; and Z is a vitamin D structure)
which comprises:[a] the step of reacting a compound having the following structure:(in the formula, W, X and Y are as defined above; Z is a steroid ring structure)with a reagent having the following structure:
E-B

80

(in the formula, E is an eliminating group)
to produce an epoxide compound having the following structure:[b] the step of treating the epoxide compound with a reducing agent to produce thecompound; and[c] the step of recovering the compound so produced."That is, the inventions are identical with each other in being a process for preparing
a desired vitamin D compound by using the alcohol compound at the 20-position of a
steroid ring structure as the starting material (Constituent Feature [B-1]), reacting said
material with a reagent to produce an epoxide compound (part of Constituent Feature[B-3], excluding the side chain-related part), and treating the epoxide compound with areducing agent (part of Constituent Feature [A-1], excluding the side chain-related part,and Constituent Features [A-2], [A-4] to [A-6], and [C] to [E]).
(B) The Corrected Invention and Exhibit Otsu 14 Invention differ in the following
points.
(Difference 1) Regarding the objective substance "Y-A'," the side chain of the Corrected
Invention is a Maxacalcitol Side Chain as indicated in the figure below on the left (theside chain-related part of Constituent Feature [A-1] and Constituent Feature [A-3]). On
the other hand, the side chain of Exhibit Otsu 14 Invention is not a Maxacalcitol Side
Chain as indicated in the figure below on the right.

(Difference 2) In the Corrected Invention, Compound "E-B" (used as a reagent; E is Br,
and B is a structure containing an epoxy group; the same applies hereinafter) is"4-bromo-2,3-epoxy-2-methylbutane" (the Reagent) having the following structure:81

(the chemical formula part of Constituent Feature [B-2]). On the other hand, in Exhibit
Otsu
14
Invention,
Compound"E-B"
is"4-bromo-2-methyl-tetrahydropyranyloxy-2-butene" having the following structure:(Difference 3) In the Corrected Invention, the starting material and Compound "E-B"
are reacted in the presence of a base to obtain an epoxide compound having thefollowing structure:n=1, R1 and R2= methyl(part of Constituent Feature [B-2], excluding the chemical formula, and the side
chain-related part of Constituent Feature [B-3]). On the other hand, in Exhibit Otsu 14
Invention, a compound having the following structure is produced through reaction of
the starting material and Compound "E-B":

and then, epoxide compounds having the following structures are produced by using the
Katsuki-Sharpless reaction:

82

Compound 18

Compound 19

D. Consideration concerning whether a person ordinarily skilled in the art can easily
conceive of Differences 2 and 3
As mentioned in C. above, the Corrected Invention and Exhibit Otsu 14 Inventiondiffer in the objective substance (Difference 1), the reagent reacted with the starting
material (Difference 2), and the epoxide compound, which is the intermediate, and thestep of producing said compound (Difference 3). The appellants allege that a person
ordinarily skilled in the art can easily conceive of the structure pertaining to theCorrected Invention by combining the reagent described in Exhibit Otsu 9 Document(the Reagent) with Exhibit Otsu 14 Invention.
(A) However, as the reagent of Exhibit Otsu 14 Invention differs from the reagent of theCorrected Invention, a person ordinarily skilled in the art needs to be motivated to use
the reagent of the Corrected Invention in place of the reagent of Exhibit Otsu 14
Invention in order to conceive of the Corrected Invention from Exhibit Otsu 14
Invention. In this regard, although the structure of the Reagent itself was publicly
known (Exhibit Otsu 9), according to what is described in A. above, the processdescribed in Figure 9 of Exhibit Otsu 14 Document (Exhibit Otsu 14 Invention) is amanufacturing process for selectively synthesizing anticipated metabolites ofmaxacalcitol (12) and (13) which have a side chain end structure including two kinds ofsteric configurations, unlike maxacalcitol. Then, in Exhibit Otsu 14 Invention, theKatsuki-Sharpless reaction (by using said reaction, a side chain including a double bondis subjected to asymmetric epoxidation, and thereby, two kinds of compounds that differ
in the steric configuration can be synthesized) is used for the purpose of selectively
producing two kinds of epoxide compounds (18) and (19) (these compounds areisomers that differ in the steric configuration of the end of the side chain[R-stereoisomer and S-stereoisomer]) to synthesize the aforementioned two kinds ofanticipated metabolites of maxacalcitol. A specific reagent having a double bond at its
side chain (4-bromo-2-methyl-tetrahydropyranyloxy-2-butene) is selected as a reagent

83

used for introducing a double bond that is necessary for the Katsuki-Sharpless reaction
into the side chain of the starting material. Using the Reagent in place of said reagent isneither described nor suggested in Exhibit Otsu 14 Document and Exhibit Otsu 9
Document.
In that case, a person ordinarily skilled in the art cannot be considered to be
motivated to combine the Reagent with Exhibit Otsu 14 Invention. Therefore, thestructure of the Corrected Invention pertaining to Difference 2 (difference in thereagent) cannot be considered to be one which a person ordinarily skilled in the art
could have easily conceived of.
(B) In addition, neither Exhibit Otsu 14 Document nor other publicly known documents
submitted in this lawsuit describe or suggest any motivation of a person ordinarily
skilled in the art to intend to obtain an epoxide compound, which is the intermediate of
the Corrected invention, in place of the epoxide compound of Exhibit Otsu 14
Invention.
Therefore, the structure of the Corrected Invention pertaining to Difference 3(difference in the epoxide compounds) cannot also be considered to be one which aperson ordinarily skilled in the art could have easily conceived of.
E. Regarding the appellants' allegations
In response to the above, the appellants allege as follows: It is easy to change theobjective substance of Exhibit Otsu 14 Invention from the anticipated metabolites ofmaxacalcitol to maxacalcitol whose structure of the side chain is very similar to those of
the anticipated metabolites of maxacalcitol (Difference 1); in that case, [i] when seeing
Figure 9 of Exhibit Otsu 14 Document, a person ordinarily skilled in the art, who
considers an efficient process for preparing maxacalcitol, can conceive of using and ismotivated to use compounds in which the hydromethyl group of epoxide compounds(18) and (19) is replaced with a methyl group as the precursors of maxacalcitol for the
purpose of synthesizing maxacalcitol, focusing attention on the fact that the structuresof the side chains of the anticipated metabolites of maxacalcitol indicated in said figure
and the structure of a Maxacalcitol Side Chain are very similar to each other (hereinafterreferred to as "Allegation [i]"); [ii] by applying retrosynthesis and common generaltechnical knowledge to such replaced epoxide compounds, a person ordinarily skilled in
the art conceives of first cutting between the oxygen atom of the ether bond and thecarbon atom on its right side and then reacting the Reagent obtained by the cutting andthe starting material of Exhibit Otsu 14 Invention, and also considers that the reaction
between said materials proceeds well; therefore, it is easy for a person ordinarily skilledin the art to conceive of both of the structures of the Corrected Invention pertaining to84

Differences 2 and 3 (hereinafter referred to as "Allegation [ii]"). The appellants'
allegations are considered below.
(A) As mentioned in Allegation [i], the appellants allege that a person ordinarily skilledin the art, who considers an efficient process for preparing maxacalcitol, can conceiveof using and is motivated to use compounds in which the hydromethyl group of epoxide
compounds (18) and (19) is replaced with a methyl group as the precursors of
maxacalcitol based on Figure 9 of Exhibit Otsu 14 Document.
However, as mentioned in D.(A) above, the process described in Figure 9 of Exhibit
Otsu 14 Document is a manufacturing process for selectively synthesizing two different
kinds of anticipated metabolites of maxacalcitol (12) and (13), which differ in that thesteric configuration at the 25-position is R-stereoisomer or S-stereoisomer. The process
comprises a series of steps: specifically, the step of first carrying out the two-stepreaction of introducing a side chain having a double bond by applying a reagent to thestarting material and using the Katsuki-Sharpless reaction to selectively synthesize twokinds of epoxide compounds (18) and (19), which are intermediates in which the doublebond is converted into an epoxy group; the step of then opening the ring of the epoxy
group of each epoxide compound to produce two kinds of steroid compounds asgraphically illustrated in the lower right of Figure 9; and the final step of subjecting
each of the steroid compounds to light illumination and thermal isomerization to
produce the aforementioned anticipated metabolites (12) and (13), which are the final
objective substances, from each of these steroid compounds. In the aforementioned
Allegation [i] of the appellants, they only extract the point that the process goes througha step involving epoxide compounds as the intermediates (precursors) in the final phaseof the series of steps, and allege that the steps before obtaining said epoxide compounds
are changed to those that completely differ from those of Exhibit Otsu 14 Invention.
Therefore, it requires a technical idea of focusing attention especially on the point thatthe process goes through a step involving epoxide compounds out of the series of stepsof Exhibit Otsu 14 Invention (given that one intends to apply this Exhibit Otsu 14
Invention to the synthesis of maxacalcitol, it is natural for him/her to conceive of amanufacturing process using 4-bromo-2-methyl-2-butene (prenyl bromide) indicated in
the following figure, which does not have a tetrahydropyranyloxy group (OTHP group)that is excess for a Maxacalcitol Side Chain, in place of 4-bromo-2-methyltetrahydropyranyloxy-2-butene, as the reagent of Exhibit Otsu 14 Invention, and otherthan this, going through a series of steps, specifically, the step of introducing a side
chain, the epoxidation step, and the step of opening the ring of the epoxy group, which
are the same as those of Exhibit Otsu 14 Invention).

85

Reagent described in Exhibit Otsu 14 Document

4-bromo-2-methyl-2-butene

In this regard, in Exhibit Otsu 14 Document, there is no statement suggesting thatthe series of steps indicated in Figure 9 is focused on the point that the process goes
through a step involving epoxide compounds. Rather, it is considered that the epoxide
compounds were produced during the steps just as a result of adopting the
Katsuki-Sharpless reaction for the purpose of selectively synthesizing two kinds ofanticipated metabolites of maxacalcitol (12) and (13), which differ in the stericconfiguration of the end of the side chain of which the 26-position is hydroxylated. In
addition, Exhibit Otsu 14 Document only describes that anticipated metabolites ofmaxacalcitol were obtained in a good yield by the synthesis process indicated in Figure
9. There is neither statement describing problems nor statement suggesting the points
which are not required to be changed and which should be improved when improving(changing) the series of steps of Exhibit Otsu 14 Invention (even if the issue of thenumber of steps is taken up as a point to be improved, there is no suggestion about
which step should be cut down, the step of introducing a side chain, the epoxidation step,or the step of opening the ring of the epoxy group, and it is also possible to assume an
option of direct hydroxylation from a double bond without going through epoxidation).
In that case, even if a person ordinarily skilled in the art could have conceived ofapplying Exhibit Otsu 14 Invention to the synthesis of maxacalcitol based on similarity
between the side chains of the anticipated metabolites of maxacalcitol that are the final
objective substances of Exhibit Otsu 14 Invention (or the steroid compounds that are theprecursors thereof) and a Maxacalcitol Side Chain, he/she is not recognized as having
been able to easily conceive of changing the step of introducing a side chain and theepoxidation step, which are steps before the step of opening the ring of the epoxy groupof the epoxide compounds that is the final step, without changing said step of opening
the ring of the epoxy group of the epoxide compounds, focusing special attention on the
point that the process goes through a step involving epoxide compounds out of theseries of steps.
(B) In this regard, the appellants allege as follows as a ground for Allegation [i]: Exhibit
Otsu 19 Document (International Publication No. 1993/21204) describes that an
epoxide compound is used when forming the same side chain as that of calcitriol, andthe inventors of the Corrected Invention themselves also conceived of maxacalcitol by86replacing the carbon atom at the 22-position of the side chain of calcitriol with an
oxygen atom; therefore, a person ordinarily skilled in the art, who has the technicalknowledge of Exhibit Otsu 19 Document, has no difficulty in conceiving of the idea ofsynthesizing the precursors of maxacalcitol (epoxide compounds) from the epoxide
compounds of Exhibit Otsu 14 Invention.
However, as indicated in the figure below, Exhibit Otsu 19 Document describes a
process for the synthesis of calcitriol wherein the 22-position of the side chain is bonded
not by an oxygen atom but by a carbon atom (it is not bonded by an ether bond unlike a
Maxacalcitol Side Chain) (Exhibit Otsu 19 and the entire import of argument). The
Williamson reaction between the alcohol compound at the 20-position and the reaction
reagent is not carried out, and the objective substance is not maxacalcitol.
The 22-position is
not an oxygen atom.

<Reaction of Exhibit Otsu 19>

Oxidation

Reduction

Compound (VI)

In addition, as mentioned above, the manufacturing process described in Exhibit
Otsu 19 Document comprises a series of steps, specifically, the step of oxidizing the
double bond of the side chain of the starting material to introduce an epoxy group into
the side chain and the step of opening the ring of the epoxy group of the epoxide
compound with a reducing agent to produce the side chain of the objective substance. It
is not recognized that there is a statement suggesting that attention is focused only on
the point that the process goes through a step involving the epoxide compound as theintermediate out of said steps.
In that case, even a person ordinarily skilled in the art, who has the technicalknowledge of Exhibit Otsu 19 Document, cannot be considered to have been able toeasily conceive of the idea of changing the step of introducing a side chain and theepoxidation step, which are steps before the final step of the synthesis of the objective
substance, focusing attention only on the point that epoxide compounds are used as the
precursors in said final step, based on the series of steps of Exhibit Otsu 14 Invention.
Incidentally, the appellants also point out that the inventors of the Corrected
Invention themselves said that they considered the synthesis of a substance by replacing
the carbon atom at the 22-position of calcitriol with an oxygen atom and thereby
invented maxacalcitol (Exhibit Otsu 14). However, even if the inventors considered as87

such, this fact does not serve as a ground for proving that it is easy for a person
ordinarily skilled in the art to conceive of a process for preparing maxacalcitol bychanging the step of introducing a side chain and the epoxidation step, which are steps
before the final step in the aforementioned process for preparing calcitriol, focusing
attention only on the point that epoxide compounds are used as the precursors in said
final step.
(C) The appellants also allege as follows: [a] A person ordinarily skilled in the art, whosees Figure 9 of Exhibit Otsu 14 Document, can understand that the Katsuki-Sharpless
reaction is used due to existence of two different kinds of steric configurations and thatsuch issue of steric configuration does not arise in relation to maxacalcitol; therefore,
existence of two kinds of isomers in Figure 9 does not reduce the easiness of conceivingof the idea alleged by the appellants; [b] A person ordinarily skilled in the art would not
bother to adopt a roundabout synthesis process which comprises a larger number ofsteps; therefore, he/she never adopts a process wherein the reagent is replaced withprenyl bromide when applying Exhibit Otsu 14 Invention to the synthesis of
maxacalcitol.
However, regarding the allegation of [a] above, it is not recognized that similarity inthe structures of the side chains and Exhibit Otsu 19 Document, which are originallyalleged by the appellants as the grounds for the easiness of conceiving of the idea, aresufficient to have a person ordinarily skilled in the art conceive of extracting only the
point that the process goes through a step involving epoxide compounds as theintermediates (precursors) out of the series of steps described in Figure 9 of Exhibit
Otsu 14 Document and changing the steps before obtaining said epoxide compounds tothose that are completely different from those of Exhibit Otsu 14 Invention, as indicatedin the holdings in (A) and (B) above. Even if a person ordinarily skilled in the art, whosees the steps of Figure 9 of Exhibit Otsu 14 Document, can have an understanding as
alleged above by the appellants, this fact cannot be considered to suggest that a person
ordinarily skilled in the art focuses attention on the point that the process goes throughthe step involving epoxide compounds as the intermediates out of the series of steps,
and it thus does not affect the content of said holdings.
In addition, regarding the allegation of [b] above, as indicated in the holding in (A)above, even if it can be said that a person ordinarily skilled in the art, who intends toapply Exhibit Otsu 14 Invention to the synthesis of maxacalcitol, naturally conceives ofchanging the structure of the side chain of the reagent within the limits of difference inthe structures of the side chains of the final objective substances due to said difference,he/she is not recognized as being motivated to maintain only the step involving epoxide

88compounds out of the series of steps and change the synthesis steps before said step tocompletely different ones for the purpose of further reducing the number of steps.
Therefore, said allegation of the appellants also does not affect the content of said
holding.
(D) On these bases, regarding the appellants' allegations, Allegation [i] is originallyunacceptable. Therefore, it is not recognized that a person ordinarily skilled in the art
could have easily conceived of the structures of the Corrected Invention pertaining to
Differences 2 and 3 based on Exhibit Otsu 14 Invention, without the need of
considering another Allegation [ii].
F. Therefore, there is no reason for the appellants' allegation of Ground for Invalidation
A.
(2) Regarding lack of an inventive step by citing Exhibit Ko 12 Document as theprimarily cited document (Ground for Invalidation B)
A. Content described in Exhibit Ko 12 Document
Exhibit Ko 12 Document (the translation thereof is Exhibit Otsu 43) is a paper titled"Synthetic studies of vitamin D3 analogues VIII," which was written by five researchersof the new medicine research laboratory of the appellee, including Noboru Kubodera,
who is one of the inventors of the Corrected Invention. The paper was published in"Chem. Pharm. Bull." which was distributed in 1986 prior to the Priority Date
(September 3, 1996). There are following statements in the paper.
(A) "In contrast to the formation of [compound] 10, attempted alkylation of 9 with
1-bromo-3,3-ethylenedioxybutane … failed. [note in this judgment: see Reaction
Formula A] (note 10)" (fifth line from the bottom of page 2 to the third line from thebottom thereof)[Reaction Formula A]

The alkylation failed.
(B) "However, the desired 25-keto derivative (13) was obtained by the following
two-step procedure; the alcohol 9 was treated with 4-bromo-1-butene and a large excess
of NaH in refluxing xylene for 18 h, then the resulting 1:1 mixture of the double bondisomers (11 and 12) was oxidized by the Wacker process (catalytic amounts of PdCl289and excess CuCl in DMF-H2O, O2 atmosphere, room temperature, 19 h) to give the
ketone (13) in 44% yield based on the consumed [compound] 9, together with theunchanged isomer 12. The reaction of [compound] 13 with MeMgBr in THF at 0°C for
1 h gave the pro-D3 derivative (14) in 79% yield.
[Compound] 14 was successively subjected to the irradiation, thermal isomerizationand deprotection in the same manner as mentioned above to give
1α,25-(OH)2-22-oxa-D3 3b in 9% yield [note in this judgment: see Reaction FormulaC]." (third line from the bottom of page 2 to line 10 of page 3)[Reaction Formula C](C) (Note 10) "The alkylation of 1α,3β-bis(tetrahydropyranyloxy)-5-androsten-17β-olwith 1-chloro-4,4-ethylenedioxypentane in the presence of NaH in boiling xylene gave
the desired ether in good yield [note in this judgment: see Reaction Formula B]. The
failure in this work might be due to the bulkiness of 1-halo-3,3-ethylenedioxybutane
compared with the former one." (seventh line from the bottom of page 5 to the third linefrom the bottom thereof)[Reaction Formula B]901-chloro-4,4ethylenedioxypentane
1α,3β-bis(tetrahydropyranyloxy)5-androsten-17β-ol

B. Content of Exhibit Ko 12 Invention
According to A.(A) above, Exhibit Ko 12 Document is recognized as disclosing thefollowing process (Exhibit Ko 12 Invention).
"A manufacturing process for the synthesis of a steroid compound having a
Maxacalcitol Side Chain wherein Compound 9 (alcohol compound at the 20-position ofa steroid ring structure) of Reaction Formula A was reacted with
1-bromo-3,3-ethylenedioxybutane (Exhibit Ko 12 Reagent 1) but the reaction failed andthe desired compound could not be obtained"
C. Common features and differences between the Corrected Invention and Exhibit Ko
12 Invention(A) The Corrected Invention and Exhibit Ko 12 Invention are identical with each otherin the following point.
"A process for preparing a steroid compound having a Maxacalcitol Side Chain byusing the alcohol compound at the 20-position of a steroid ring structure (Constituent
Feature [B-1]) as the starting material and reacting said material with a reagent(Constituent Features [A] and [E])"(B) The Corrected Invention and Exhibit Ko 12 Invention differ in the following points.
(Difference 1) In the Corrected Invention, the compound used as the reagent (in the caseof a structure containing an epoxy group wherein the eliminating group is Br) is
1-bromo-3-methyl-2,3-epoxybutane (the Reagent) (the chemical formula part ofConstituent Feature [B-2]). On the other hand, in Exhibit Ko 12 Invention, thecompound used as the reagent is 1-bromo-3,3-ethylenedioxybutane (Exhibit Ko 12
Reagent 1).
(Difference 2) The Corrected Invention is a process for obtaining the objective
substance which comprises the step of reacting the starting material and the reagent in
the presence of a base to obtain an epoxide compound and the step of subsequently
treating the epoxide compound with a reducing agent to open the ring of the epoxy
group (part of Constituent Feature [B-2], excluding the chemical formula part, andConstituent Features [B-3] [C], and [D]). On the other hand, in Exhibit Ko 12 Invention,

91

the starting material and the reagent were reacted, but the reaction failed and theobjective substance could not be obtained.
D. Consideration concerning whether a person ordinarily skilled in the art can easily
conceive of Difference 1
As mentioned in C. above, the Corrected Invention and Exhibit Ko 12 Inventiondiffer in the reagent reacted with the starting material (Difference 1) and the point of
whether the starting material and the reagent react and thereby lead to the synthesis ofan epoxide compound, which is the intermediate, and the objective substance(Difference 2). The appellants allege that a person ordinarily skilled in the art can easily
conceive of the structures of the Corrected Invention pertaining to the differences bycombining the Reagent of Exhibit Otsu 9 Document with Exhibit Ko 12 Invention.
However, as the reagent of Exhibit Ko 12 Invention differs from the reagent of theCorrected Invention, a person ordinarily skilled in the art is required to have amotivation to use the reagent of the Corrected Invention in place of the reagent of
Exhibit Ko 12 Invention in order to conceive of the Corrected Invention based on
Exhibit Ko 12 Invention. In this regard, although the structure of the Reagent itself was
publicly known (Exhibit Otsu 9), Exhibit Ko 12 Reagent 1 (left figure below)
completely differs from the Reagent (right figure below) in the specific cyclic structure.
In addition, neither Exhibit Ko 12 Document nor Exhibit Otsu 9 Document describes orsuggests that the Reagent is used in place of Exhibit Ko 12 Reagent 1 with which thereaction failed.

In that case, it cannot be said that a person ordinarily skilled in the art has amotivation to combine the Reagent with Exhibit Ko 12 Invention. Therefore, it cannot
be said that a person ordinarily skilled in the art could have easily conceived of thestructure of the Corrected Invention pertaining to Difference 1 (difference in thereagent).
E. Regarding the appellants' allegations
In response to the above, the appellants allege as follows: [i] As of the Priority Date,a person ordinarily skilled in the art only had to find an alkylation reagent which canalkylate the hydroxyl group of the Steroid Starting Material in a good yield; [ii] If aperson ordinarily skilled in the art, who saw Exhibit Ko 12 Invention, sees the statement
in note 10 of Exhibit Ko 12 Document, he/she can conceive of using the Reagent, which
is a compound that has a cyclic structure while maintaining a four carbon straight alkyl

92

structure and whose number of elements that constitute the cyclic part is reduced, as thealkylation reagent in place of Exhibit Ko 12 Reagent 1 with which alkylation reaction
failed; [iii] Then, seeing Exhibit Otsu 9 Document that describes the Reagent, a person
ordinarily skilled in the art considers that the reaction between the Reagent and theSteroid Starting Material proceeds well; therefore, a person ordinarily skilled in the art
can easily conceive of the structures of the Corrected Invention pertaining to
Differences 1 and 2.
(C) However, regarding the aforementioned allegation [i] of the appellants, it is notrecognized that a person ordinarily skilled in the art was naturally motivated to change
the alkylation reagent of Exhibit Ko 12 Invention to another alkylation reagent and was
also motivated to seek an alkylation reagent that replaces Exhibit Ko 12 Reagent 1
based on the step that failed to introduce a Maxacalcitol Side Chain, by daringly
focusing attention on said step out of the processes described in Exhibit Ko 12
Document, if taking into account that Exhibit Ko 12 Document describes as follows:
The reaction of Exhibit Ko 12 Invention failed; therefore, 4-bromo-1-butene (Exhibit
Ko 12 Reagent 2) was applied to Compound 9 as a process for preparing maxacalcitol
in place of said reaction; in that case, alkylation reaction proceeded, and steroid
compound (14) having a Maxacalcitol Side Chain could be synthesized by going
through 25-keto derivative (13) (Reaction Formula C in A.(B) above).
(B) In addition, considering the aforementioned allegation [ii] of the appellants, it isstated in parallel in note 10 of Exhibit Ko 12 Document that Reaction Formula B
achieved a good yield but that Reaction Formula A failed. It is specifically stated that
"The failure in this work might be due to the bulkiness of
1-halo-3,3-ethylenedioxybutane compared with the former one." The "former one"mentioned here is recognized as meaning "1-chloro-4,4-ethylenedioxypentane" (Exhibit
Ko 12 Reagent 3) of Reaction Formula B.
Comparing the reagents used in the aforementioned two reactions, the number ofcarbons of the main chain of Exhibit Ko 12 Reagent 1 (left figure below) with whichalkylation failed is one fewer than that of Exhibit Ko 12 Reagent 3 (right figure below)
with which alkylation succeeded, and the position at which a five-membered ring isbonded is closer to bromide, which is an eliminating group. Therefore, it is reasonable
to understand that "bulkiness" includes the perspective of distance between theeliminating group and the cyclic structure and does not merely mean the size of thecyclic structure.

93

Reaction site

Reaction site

1-bromo-3,3-ethylenedioxybutane

1-chloro-4,4-ethylenedioxypentane

Moreover, the statement in note 10 of Exhibit Ko 12 Document is nothing more thananalyzing that the failure "might be due to the bulkiness." In addition, Reaction Formula
B originally differs from Reaction Formula A not only in the reagent but also in the
structure of the starting material. Therefore, the statement cannot be understood assuggesting that the reaction of Reaction Formula A naturally proceeds in the samemanner as that of Reaction Formula B and the reagent of Reaction Formula A reacts
with Compound 9 if the reagent of Reaction Formula A is changed to a reagent obtainedby reducing the "bulkiness" of Exhibit Ko 12 Reagent 1.
Even based on the understanding that the "bulkiness" of Exhibit Ko 12 Reagent 1 isthe "size of the cyclic structure" and that it inhibits the reaction, there is no statement
suggesting that the reagent should maintain the cyclic structure in Exhibit Ko 12
Document. Rather, as mentioned above, 4-bromo-1-butene (Exhibit Ko 12 Reagent 2;
see the following figure), which is used in the working example in which the reaction
succeeded in Exhibit Ko 12 Document, does not have a cyclic structure. Therefore, itcannot be said that a person ordinarily skilled in the art conceives of a reagent
maintaining a cyclic structure as a reagent with reduced "bulkiness."

Therefore, there is no reason for the appellants' allegation that note 10 in Exhibit Ko
12 Document suggests that alkylation reaction can be expected to proceed in relation to
Compound 9 if the five-membered ring cyclic ether of Exhibit Ko 12 Reagent 1 is lessbulky, that is, a compound whose number of elements that constitute the cyclic part isreduced. Consequently, the aforementioned allegation [ii] of the appellants on thispremise is unacceptable.
(C) On these bases, it cannot be said that a person ordinarily skilled in the art had amotivation to consider the use of the Reagent whose cyclic structure is reduced in sizein place of Exhibit Ko 12 Reagent 1 based only on the suggestion that the failure "might
be due to the bulkiness," by daringly focusing attention on Exhibit Ko 12 Invention
using Exhibit Ko 12 Reagent 1 with which reaction failed as a process for preparing
maxacalcitol. It is thus not recognized that a person ordinarily skilled in the art could94have easily conceived of the structures of the Corrected Invention pertaining to
Differences 1 and 2 based on Exhibit Ko 12 Invention, without the need of consideringother points.
F. Therefore, there is no reason for the appellants' allegation of Ground for Invalidation
B.
(3) Regarding the lack of an inventive step by citing Exhibit Otsu 4 Document as theprimarily cited document (Ground for Invalidation C)
The Corrected Invention is not recognized as one which a person ordinarily skilledin the art could have easily conceived of based on the invention described in Exhibit
Otsu 4 Document. The reason therefor is as held in No. 4, 7. in "Facts and reasons" inthe judgment in prior instance. Therefore, the relevant part is cited.
3. Summary
On these bases, the Appellant's Process is recognized as falling under the technicalscope of the Corrected Invention as an equivalent to the Corrected Invention. In addition,
there is no reason for all of the grounds for invalidation alleged by the appellants inrelation to the Corrected Invention. Therefore, the Patent Pertaining to the Corrected
Invention is not recognized as one that should be invalidated by a trial for patent
invalidation.
According to the aforementioned facts on which the decision is premised, all of theAppellants' Products were prepared by the Appellant's Process. Consequently, both theact of importing or assigning Appellant's Product 1 and the act of assigning or offering
for assignment Appellants' Products 2 constitute infringement of the Patent Right.
Therefore, there is a reason for all of the appellee's claims for an injunction against theimport or assignment of Appellant's Product 1 and disposal thereof in relation toAppellant DKSH and claims for an injunction against the assignment or offer forassignment of Appellants' Products 2(1) to (3) and disposal thereof in relation toAppellant Iwaki Seiyaku, Appellant Takata Pharmaceutical, and Appellant Pola Pharma,
respectively, for the period up to September 3, 2017, which is the last day of theduration of the Patent Right before the registration of extension of the duration of the
Patent Right.
No. 5 Conclusion
On these bases, the judgment in prior instance that upheld all of the appellee's
claims is reasonable, and there is no reason for all of the appeals in question filed by theappellants.
Therefore, the judgment shall be rendered in the form of the main text.
Intellectual Property High Court, Special Division

95

Presiding judge: SHITARA Ryuichi
Judge: SHIMIZU Misao
Judge: TAKABE Makiko
Judge: OTAKA Ichiro
Judge: OHYORI Asayo

96

(Attachment)
Process List
A process for preparing maxacalcitol comprising the following steps:
1. (Step I) The step of reacting the following Starting Material A with the following
Reagent B in the presence of a base to synthesize the following Intermediate C of an
epoxide compound
Starting Material A+ Reagent B→ Intermediate C97

2. (Step II) The step of opening the epoxide ring (epoxy group) by treating the following
Intermediate C with a reducing agent to obtain the following Substance D
Intermediate C→

Substance D

3. (Step III) The step of converting the following trans-form Substance D to a cis form
and removing protective groups to obtain maxacalcitol
Substance D→

Maxacalcitol

4. (Step IV) The step of recovering the obtained maxacalcitol(Note: In each of the aforementioned structural formulas, Pro means a "protective
group.")

98