PATENT COOPERATION TREATY
`
`PCT
`
`INTERNATIONAL PRELIMINARY REPORT ON PATENTABILITY
`
`(Chapter I of the Patent Cooperation Treaty)
`
`(PCT Rule 44bis)
`
`Applicant’s or agent’s file reference
`3685.043PC01
`
`FOR FURTHER ACTION
`
`See item 4 below
`
`International filing date (day/month/yeGE)
`International application No.
`20 July 2017 (20.07.2017)
`PCT/U82017/043103
`International Patent Classification (8th edition unless older edition indicated)
`See relevant information in Form PCT/ISA/237
`
`Priority date (day/month/yeCIE)
`20 July 2016 (20.07.2016)
`
`Applicant
`ABBVI E INC.
`
`This international preliminary report on patentability (Chapter I) is issued by the International Bureau on behalf of the
`International Searching Authority under Rule 44 bis.1(a).
`
`This REPORT consists of a total of 8 sheets, including this cover sheet.
`
`I11 the attached sheets, any reference to the written opinion of the International Searching Authority should be read as a
`reference to the international preliminary report on patentability (Chapter I) instead.
`
`This report contains indications relating to the following items:
`
`Box \o. I
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`Basis of the report
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`Box \o. II
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`Box \o.
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`
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`Priority
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`Non—establishment of opinion with regard to novelty, inventive step and industrial
`applicability
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`Lack of unity of invention
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`Reasoned statement under Article 35(2) with regard to novelty, inventive step or
`industrial applicability; citations and explanations supporting such statement
`
`Certain documents cited
`
`Certain defects in the international application
`
`Certain observations on the international application
`
`lhe International Bureau will communicate this report to designated Offices in accordance with Rules 44bis.3(c) and 93bis.1
`but not, except where the applicant makes an express request under Article 23(2), before the expiration of 30 months from
`the priority date (Rule 44bis .2).
`
`The International Bureau of WIPO
`34, chemin des Colombettes
`1211 Geneva 20, Switzerland
`Facsimile NO. +41 22 338 82 70
`Form PCT/IB/373 (January 2004)
`
`Date of issuance of this report
`22 January 2019 (22.01.2019)
`
`AthHZEd officer
`
`-
`XlaOfan Tang
`e—mail; pct.[eam2@wip0.int
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`
`
`
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`Box \o.
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`Box \o.
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`Box \o.
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`Box \o.
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`Box \o.
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`

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`PATENT COOPERATION TREATY
`
`From the
`INTERNATIONAL SEARCHING AUTHORITY
`
`see form PCT/ISA/220
`
`
`
`PCT
`
`WRITTEN OPINION OF THE
`INTERNATIONAL SEARCHING AUTHORITY
`
`(PCT Rule 43bis.1)
`
`
`Date of mailing
`(day/month4/ear)
`
`see form PCT/ISA/210 (second sheet)
`
`
`
`Applicant's or agent‘s file reference
`see form PCT/ISA/220
`
`FOR FURTHER ACTION
`See paragraph 2 below
`
`International application No.
`PCT/US2017/043103
`
`International filing date (day/fnonth/year)
`20.07.2017
`
`Priority date (day/month4/ear)
`20.07.2016
`
`
`
`
`
`ABBVIE INC 1.
`
`
`International Patent Classification (IPC) or both national classification and IPC
`INV. A61 K9/00 A61K47/10 A61K47/32 A61K47/38 A61K31/195 A61K31/198 A61P25/16
`
`
`Applicant
`
`This opinion contains indications relating to the following items:
`
`Box No. I
`
`Basis of the opinion
`
`Box No. II
`
`Priority
`
`ROOKIE Box No. V
`KNEE Box No. VIII Certain observations on the international application
`
`Box No. III
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`Non-establishment of opinion with regard to novelty, inventive step and industrial applicability
`
`Box No. IV
`
`Box No. VI
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`Lack of unity of invention
`Reasoned statement under Rule 43bis.1(a)(i) with regard to novelty, inventive step and industrial
`applicability; citations and explanations supporting such statement
`Certain documents cited
`
`Box No. VII
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`Certain defects in the international application
`
`2.
`
`FURTHER ACTION
`
`If a demand for international preliminary examination is made, this opinion will usually be considered to be a
`written opinion of the International Preliminary Examining Authority ("IPEA") except that this does not apply where
`the applicant chooses an Authority other than this one to be the IPEA and the chosen IPEA has notifed the
`International Bureau under Rule 66.1bis(b) that written opinions of this International Searching Authority
`will not be so considered.
`
`If this opinion is, as provided above, considered to be a written opinion of the IPEA, the applicant is invited to
`submit to the IPEA a written reply together, where appropriate, with amendments, before the expiration of 3 months
`from the date of mailing of Form PCT/ISA/22O or before the expiration of 22 months from the priority date,
`whichever expires later.
`
`For further options, see Form PCT/ISA/220.
`
`
`
`F
`Date of completion of
`3956‘“ am""’”r.@
`this opinion
`f3 o 7%:
`see form
`European Patent Office
`9))
`g
`’
`:7
`PB. 5818 Patentlaan 2
`‘1,
`3°
`PCT/'SA’ZIO
`NL-2280 HV Rijswijk - Pays Bas
`Telephone No. +31 70 340-0
`teamwmw-w‘l
`Tel- +31 70 340 - 2040
`'
`Fax: +31 70 340 - 3016
`
`
`
`
`Authorized Officer
`
`Fre|ichowska, J
`
`
`
`Name and mailing address of the ISA:
`
`Form PCT/ISA/237 (Cover Sheet) (January 2015)
`
`

`

`WRITTEN OPINION OF THE
`INTERNATIONAL SEARCHING AUTHORITY
`
`International application No.
`PCT/U82017/043103
`
`Box No. I Basis of the opinion
`
`1. With regard to the language, this opinion has been established on the basis of:
`
`IZI
`
`El
`
`the international application in the language in which it was filed.
`
`a translation of the international application into , which is the language of a translation furnished for the
`purposes of international search (Rules 12.3(a) and 23.1 (b)).
`
`This opinion has been established taking into account the rectification of an obvious mistake authorized
`by or notified to this Authority under Rule 91 (Rule 43bis.1(a))
`
`With regard to any nucleotide and/or amino acid sequence disclosed in the international application, this
`opinion has been established on the basis of a sequence listing:
`
`a. El
`
`forming part of the international application as filed:
`
`CI
`
`in the form of an Annex C/ST.25 text file.
`
`[I on paper or in the form of an image file.
`
`b. El furnished together with the international application under PCT Rule 13ter.1(a) for the purposes of
`international search only in the form of an Annex C/ST.25 text file.
`
`c. D furnished subsequent to the international filing date for the purposes of international search only:
`
`CI
`
`in the form of an Annex C/ST.25 text file (Rule 13ter.1(a)).
`
`El on paper or in the form of an image file (Rule 13ter.1(b) and Administrative Instructions, Section
`713).
`
`4.I:I
`
`In addition, in the case that more than one version or copy of a sequence listing has been filed or furnished,
`the required statements that the information in the subsequent or additional copies is identical to that
`forming part of the application as filed or does not go beyond the application as filed, as appropriate, were
`furnished.
`
`5. Additional comments:
`
`Form PCT/ISA/237 (January 2015)
`
`

`

`WRITTEN OPINION OF THE
`INTERNATIONAL SEARCHING AUTHORITY
`
`International application No.
`PCT/U82017/043103
`
`Box No. V Reasoned statement under Rule 43bis.1(a)(i) with regard to novelty, inventive step or
`industrial applicability; citations and explanations supporting such statement
`
`1. Statement
`
`Novelty (N)
`
`Inventive step (IS)
`
`Industrial applicability (IA)
`
`2. Citations and explanations
`
`see separate sheet
`
`Yes: Claims
`No:
`Claims
`
`1-42
`
`Yes: Claims
`No:
`Claims
`
`Yes: Claims
`No:
`Claims
`
`1-42
`
`1-42
`
`Box No. VI Certain documents cited
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`1. Certain published documents (Rules 43bis.1 and 70.10)
`
`and / or
`
`2. Non-written disclosures (Rules 43bis.1 and 70.9)
`
`see form 210
`
`Box No. VIII Certain observations on the international application
`
`The following observations on the clarity of the claims, description, and drawings or on the question whether the
`claims are fully supported by the description, are made:
`
`see separate sheet
`
`Form PCT/ISA/237 (January 2015)
`
`

`

`WRITTEN OPINION OF THE
`
`INTERNATIONAL SEARCHING
`
`International application No.
`
`AUTHORITY (SEPARATE SHEET)
`
`PCT/U82017/O43103
`
`Re Item V
`
`Reasoned statement with regard to novelty, inventive step or industrial
`
`applicability; citations and explanations supporting such statement
`
`Cited documents
`
`Reference is made to the following documents:
`
`05 5 635 213 A (NYSTROM CHRISTER [SE] ET AL) 3 June 1997
`
`wo 2016/036308 A1 (LOBSOR PHARMACEUTICALS AKTIEBOLAG
`
`[SE]) 10 March 2016 (2016-03-10)
`
`wo 2016/118556 A1 (ABBVIE INC [US]) 28 July 2016, P-doc
`
`05 3 927 205 A (OHNO YOSHITOMO ET AL) 16 December 1975
`
`D1
`
`D2
`
`03
`
`D4
`
`M!
`
`The subject-matter of claims 1-42 is new in the sense of Article 33(2) PCT.
`
`None of the prior art documents discloses a pharmaceutical composition suitable for
`
`intraduodenal administration comprising:
`
`(a) levodopa 4.0 w/w %;
`
`(b) carbidopa 1.0 w/w %;
`
`(c) a polymer-based suspending agent in an amount of about 0.1 w/w % to about 5 w/
`
`w % of the total composition; and
`
`(d) a liquid vehicle selected from water, polyethylene glycol, or a mixture of water and
`
`polyethylene glycol.
`
`Inventive step
`
`The present application does not meet the criteria of Article 33(1) PCT, because the
`
`subject-matter of claims 1-42 does not involve an inventive step in the sense of Article
`
`33(3) PCT.
`
`D1 is regarded as being the prior art closest to the subject-matter of claim 1, and
`
`discloses a pharmaceutical suspension for intraduodenal administration comprising
`
`levodopa 2%, carbidopa 0.5% and methylcellulose 1.8% (example 1) or 0.3%
`
`carbomer (Carbopol) 934P (example 2; claims 1-3). The liquid vehicle is water.
`
`Form PCT/ISA/237 (Separate Sheet) (Sheet 1) (EPO-April 2005)
`
`

`

`WRITTEN OPINION OF THE
`
`INTERNATIONAL SEARCHING
`
`International application No.
`
`AUTHORITY (SEPARATE SHEET)
`
`PCT/U82017/O43103
`
`Concerning the yield value, Table 11 of the present application indicates that a
`
`formulation comprising 0.3% Carbopol 934P (as the example 2 of D1) has a yield
`value of 6.41 Pa.
`
`The subject-matter of claim 1 therefore differs from D1 in that:
`
`- the concentration of levodopa is 4% whereas in D1 it's 2%, and
`
`— the concentration of carbidopa is 1% whereas in D1 it's 0.5%.
`
`The acceptance value of the formulations of D1 cannot be determined (see also
`
`objections under Item VIII).
`
`The application does not demonstrate any technical effect of the above defined
`differences.
`
`The problem to be solved by the present invention may therefore be regarded as how
`
`to provide an alternative formulation for intraduodenal administration comprising
`
`levodopa, carbidopa and a polymer—based suspending agent.
`
`The solution proposed in claim 1 of the present application cannot be considered to
`
`involve an inventive step (Article 33(3) PCT). Variation of active agents percentage in
`
`a formulation is a part of the usual practice of the skilled person. Therefore, provision
`
`of an alternative formulation varying merely by excipients content is obvious.
`
`Analogical reasoning applies to the subject-matter of the dependent claim 2, 11,
`
`17-20, 29, 42 (variation of percentage/concentration; purity - see also Item VIII).
`
`The features of the claims 3, 4, 6—8, 13, 21—2, 33, 34, 36, 41 are known from D1
`
`(methylcellulose, carbomer, water, particle size, preparation method).
`
`Dependent claims 5, 14-16, 35 specify the type of carbomer: Carbopol® 971 P or
`Carbopol® 974P (see also Item VIII). However, the application does not demonstrate
`any technical effect due to the choice of any of these polymers instead of Carbopol
`
`934P (as in D1). Therefore it would be obvious to replace the carbomer as in D1 by
`
`any of Carbopol® 971 P or Carbopol® 974P. Any of these polymers is known in the
`
`field of pharmaceutical formulation as being a suspending agent. Thus, it would be
`
`obvious to the skilled person to replace a carbomer with any other type of carbomer
`
`whenever the circumstances make it appropriate.
`
`Analogical reasoning applies to the subject-matter of dependent claims 9-10, 30-32,
`
`37-40 (no technical effect of the difference demonstrated). The features of said claims
`
`are considered as obvious alternatives to the compositions of D1 (different
`
`hydrocolloid, type of packaging).
`
`Form PCT/ISA/237 (Separate Sheet) (Sheet 2) (EPO-April 2005)
`
`

`

`WRITTEN OPINION OF THE
`
`INTERNATIONAL SEARCHING
`
`International application No.
`
`AUTHORITY (SEPARATE SHEET)
`
`PCT/U82017/043103
`
`Therefore, the subject—matter of claims 1—42 does not involve inventive step in view of
`D1 alone.
`
`For the analogical reasons, the subject-matter of claims 1-42 does not involve
`
`inventive step also in view of D2 alone. D2 (page 50, table 2) discloses a
`
`pharmaceutical suspension for intraduodenal administration comprising levodopa 2%,
`
`carbidopa 0.5% and NaCMC 2.92%. The liquid vehicle is water.
`
`D4 might be relevant for inventive step analysis in the further procedure. D4 discloses
`
`the combination of microcrystalline cellulose and hydrocolloids for use as suspending
`
`agents (claims 1-9).
`
`Industrial applicability
`
`The subject-matter of claims 1-42 is industrially applicable and complies with the
`
`requirements of Article 33(1) and (4) PCT.
`
`Method of treatment
`
`It is noted that when entering regional phase(s), the patentability of claim 41 can be
`
`dependent upon its precise wording / formulation. The EPO, for example, does not
`
`recognise as patentable claims directed to the medical treatment, or to the use of a
`
`compound in medical treatment, but may allow claims directed to compositions for
`
`use in a (further) medical treatment.
`
`w C
`
`ertain documents cited
`
`Above cited document WO 2016/118556 (D3) would be potentially relevant for novelty
`
`of claims 1-2 , 6, 7-8, 11, 13, 17-32, 37-42 when entering the regional/national phase.
`
`D3 discloses a pharmaceutical suspension for intraduodenal administration
`
`comprising levodopa 4%, carbidopa 1%, NaCMC 2.92% and water. The formulation is
`
`degassed with nitrogen (page 26, table 1).
`
`The subject-matter of claims 1-2 , 6, 7-8, 11, 13, 17-32, 37-42 in view of document D3
`would be therefore considered as not new.
`
`Form PCT/ISA/237 (Separate Sheet) (Sheet 3) (EPO-April 2005)
`
`

`

`WRITTEN OPINION OF THE
`
`INTERNATIONAL SEARCHING
`
`International application No.
`
`AUTHORITY (SEPARATE SHEET)
`
`PCT/U82017/043103
`
`Re Item VIII
`
`Certain observations on the international application
`
`Claims 1, 33, 37 define the subject-matter for which protection is sought by an
`
`unusual parameter: the "acceptance value". Due to introduction of this unclear
`
`parameter not only it is impossible to unambiguously determine the subject—matter for
`
`which protection is sought but it is also impossible to reliably compare the
`
`compositions of the prior art with the subject-matter of claim 1.
`
`Moreover, the features "acceptance value" and "yield value" in claim 1 are result to be
`
`achieved. This merely amounts to a statement of the underlying problem, without
`
`providing the technical features necessary for achieving this result.
`
`Also the claims 2, 29 attempt to define the subject-matter in terms of the result to be
`
`achieved, namely by stability parameters.
`
`The terms Carbopol® 971 P, Carbopol® 974P employed in claims 5, 14-16, 35 and
`
`appearing to be a registered trade mark has no precise meaning as it is not
`
`internationally accepted as a standard descriptive term, thereby rendering the
`
`definition of the subject—matter of these claims unclear, Article 6 PCT. See paragraph
`
`55 of the description for the replacement of these terms.
`
`The relative term "about" used in claims 1, 2, 6, 11, 14—21, 29, 33, 37, 42 indicates
`
`that a value can be actually different than the one disclosed in said claims and leaves
`
`the reader in doubt as to the meaning of the technical features to which it refers,
`
`thereby rendering the definition of the subject-matter of said claims unclear (Article 6
`
`PCT).
`
`Therefore, the application does not meet the requirements of Article 6 PCT.
`
`Form PCT/ISA/237 (Separate Sheet) (Sheet 4) (EPO-April 2005)
`
`