(12) INTERNATIONAL APPLICATION PUBLISHED UNDER THE PATENT COOPERATION TREATY (PCT)
`
`(l9) w"'w '~':::!':":.!:.~~ "'ll'"mo"'• •
`PCT
`
`(43) lntcrnahonal Publ1ca1Jon Date
`12 Manfl 2009 (12.03.2009)
`
`(51} lntemalional Pa lent Cla~ficafion:
`A(j/fl-l 513J5 (2006.01)
`A<ilJ 1114 (2006.01 )
`
`1111 UIIIIIIIIIUlllllllllllllllmHIHIIII
`
`(10) Inwrnutaonal Publication Nmnbcr
`WO 2009/030976 Al
`HAMEL, Jean-Bernard (llRJPll); 58, Route du \krcors,
`1'-33500 SaimCassien (PR).
`
`(21) ln14n1U1tio1.ial AppticaUon Number:
`PCT/IB'.!007/(J0343S
`
`(74) i\gcnl: Ci\BINETGERM/\IN& !\MUN.EAU; BP6153,
`F,69466 Lyon Cede 06 (FR).
`
`(22) lnteniafional Filing Dale:
`3 September 2007 (-03 09.1007)
`
`(25) filing L,mg1wge,:
`
`(26} PtihlkUlan Langi.age:
`
`English
`
`(71) Applk.~nt(fo.r llil designated Swtes u:cepi US); BECTON
`DICKlNSON ti'RANCE [FR/FRI: Rue Aiis1ide Berg~s.
`F- 38800 Por1t de Claix (f'Rj.
`
`(72} lnventors; and
`_ (75) lnveotors.lApplk nnls /for US only): BOULANGE,
`Laurmre [FR%R); Cltemin des Ch ataLgnet-s. P,38530
`Chapar~llan (HO. OOMANG-E-, Si·Y~'tioe (FRlf'RI; 11 3,
`Chem.in des Ernbles . F ,74560 Moo netier.Momex (FR).
`
`=
`
`_
`
`§
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`(81) Deslg1u1t«I. Sintcs i•mless other.vise u,Jicared. for ...,,e,y
`k.i1u( ofn(J/kmal pro1tcllo11 m,ailable}: AS. AG, AL, AM,
`AT. AU, AZ. BA, BB, BG, BH, "Bit BW, BY, BZ, CA, CH,
`CN, CO, CR. CU. CZ, DE, DK OM, 00. DZ. EC, EE. 60,
`ES. FI, 0 8, GD, GE. 0 1-1, GM, CIT. HN, HR, HU, ID, 11.,
`TN. lS. JP. KE. KG, KM, KN, KP. KR. KZ. LA, LC. LK,
`LR. L .LT. LU,LY, Mi\,MO, M B,MO, MK, MN,MW,
`MX. MY; MZ, NA, NG, NL NO, NZ. OM, PG, PH, PL,
`l>'f. RO, RS, RU, SC, SD, SE. SO. S'K, SL, SM, SV, SY,
`T J, TM, TN, TR, Tr, TZ, UA, UG , us. uz_ vc, VN, ZA,
`ZM, ZW.
`
`(M) D"slgnnt«I Stal.cs (u11iess oiJu,i-,.;,i.u itltik,iud. fdl' every•
`kind of regiOlUI/ p roui:1ion available): ARJl>O (BW, OH,
`GM, KE, LS, MW, M:Z, NA , SD, SL. SZ, 'FL. UG, ZM,
`ZW). Eurasian (AM, AZ. BY. KG, KZ. M D, RU, TI, Thi),
`
`(Co111i11Md 011 rie.tl p,1ge/
`
`(54) Title: MEDICAL DE'.iCE AND SMOOTH COATING ntEREFOR
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`-
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`--= ........ -==
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`= = --
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`w
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`(I)
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`( 5 7) Ab~tf>J cl: The invention
`rcil~les lo a medical device (1)
`comprising al least one
`frrsl
`part (2; 3) coated with a coaling
`a
`(8) having
`comp,;,sition
`comprising n1. leiist one polymer
`mal~ i'ial
`comprising polyme,(cid:173)
`the
`cbains having
`following
`repeal unit Formula (I):
`in
`which X represen ts a halogen,
`for example F, or a h ydrogen,
`and in which Y1. Yl, Y;. Y,
`iudepend~ntly
`represent
`c:ach
`a halogen, for example Cl. or a
`hydrogen, c haracU:rized in that
`the ou ler surface of said coating
`(8) has a mean roughness Ra or
`less than 2.5 J,lm , The invention
`also ;elate, o a pnn (2: 3} for
`a medical dev ice (L) intended
`to cooperate with another parl
`(3; 2) and provided with such
`a ,;;oa1ing (8).
`
`Regeneron Exhibit 1008.001
`
`

`

`WO 2009/03097 6 A 1
`
`IID IDlll lllll lllllllmHlll llll Ill lllllD rn11m1111111111111111m HI Ill
`
`Europ~an (AT, BE, BG, CH, CY, CZ, DE, DK, EE, ES. FL Publislm.'I:
`PR, GR, GR, HTJ; TH, TS, TT, l .T, l J T, T .V, MC MT, NT"• PT,,
`-
`wilh it1Htma1irmal wiardt mpnn
`PT, RO, SE, Sl, SK, 'l'RJ, OAP! (HP, HJ, CH CG, Cl, CM,
`GA , GN , GQ . GW, ML. MR, NE. SN, TD, TG).
`
`Regeneron Exhibit 1008.002
`
`

`

`WO 2009/030976
`
`PCT/IB2007 /003435
`
`Medical device and smooth coating therefor
`
`The present invention relates in general to a medical device, for
`example a syringe, comprising at least one smooth coated part, , for example a
`container and/or a piston, said parts being able to move one relative to the
`other, for example translationally and/or rotationally, when the medical device is
`operated.
`
`In this application, the term distal means the part furthest from the
`user's hand , and the term proximal means the part closest to the user's hand .
`Likewise, in this application, the term "distal direction" means the direction of
`administration, i.e., towards the patient, and the term "proximal direction"
`means direction opposite to the direction of administration, i.e., away from the
`patient.
`
`Furthermore, the container is intended to accommodate a medical
`product in the liquid, gaseous, fluid, pasty or lyophilized phase, which may have
`a variable viscosity and is therefore able to flow, particularly because of the
`pressure exerted as a result of the movement of the piston relative to the
`container. The piston is preferably made at least partially from a viscoelastic
`material so as to ensure tightness in the region of contact between the
`container and the piston. At the same time, the volume of the medical product
`contained in the medical device varies, for example decreases, according to
`the relative movement between the two parts of the medical device.
`The present invention also relat.es to a part for a medical device, this
`part being intended to cooperate with a complementary part by moving relative
`to said complementary part when the medical device is operated, said part
`being provided with a coating.
`In order to improve the slip between said parts, it has been proposed
`for the entirety of the developed surface of one of the parts to be coated with a
`coating consisting of at least one polymer material, whether this is a true
`polymer or a copolymer, comprising polymer chains including repeats of one or
`more chemical units:
`
`5
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`10
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`15
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`20
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`25
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`30
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`Regeneron Exhibit 1008.003
`
`

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`WO 2009/030976
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`PCT/IB2007 /O!t3435
`
`2
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`5
`
`10
`
`in which X represents a halogen, for example F, or a hydrogen,
`and in which Y1, Y2, Y-.), Y4 each independently represent a halogen, for
`example Cl, or a hydrogen.
`For example, the polymer material is chosen from the group
`consisting of poly(p-xylylene) polymers, which may or may not be substituted,
`and in particular, poly(p-xylylene), poly(p-meta-chloroxylylene), poly(p-ortho-
`chloro/meta-chloroxylylene) and poly(p-difluoroxylylene). The
`latter
`four
`polymer materials are manufactured and sold by UNION CARBIDE
`CORPORATION, or by SPECIALTY COATING SYSTEMS, under the names
`Parylene N, Parylene C, Parylene D and Pary!ene AF4, respectively.
`For information regarding the synthesis of these particular polymer
`15 materials, particularly using chemical vapour polymerization (CVP) , on their
`various properties and on their main uses or applications, reference_. may
`usefully be made to the following documents, the respective contents of which
`are
`incorporated as
`required
`into
`this description: US 3,288,728, US
`3,342,754, US 3,379,803, US 3,472,795, US 4,225,647, US 3,300,332 and US
`6,270,872.
`These polymer materials have various properties, for example
`imperviousness to gases, for example oxygen, and to dry-lubricating liquids, for
`example water, which make them particularly attractive for use in numerous
`biomedical applications, particularly for certain medical devices.
`Unlike a conventional polymer material, a polymer material of the
`poly(p-xylylene) type is not employed by injection, dissolving or suspending in a
`solvent, but is used by depositing it onto the part by a direct dry vacuum
`deposition process using the following protocol:
`(a) use is made of a polymerization intermediate of the polymer
`30 material, in this instance of a cyclic dimer form of the aforementioned chemical
`unit, in solid and divided form,
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`20
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`25
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`Regeneron Exhibit 1008.004
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`

`

`WO 2009/030976
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`PCT/IB2007 /O!t3435
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`3
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`(b) the dimer is vaporized under vacuum (1 mm of mercury for
`example) and at approximately 150°G for example,
`(c) the vaporized dimer is then pyrolized, still under vacuum but at a
`higher temperature, for example at 650°C, in order to obtain the reactive
`5 monomer form corresponding to the aforementioned dimer and to the afore(cid:173)
`mentioned chemical unit, and
`the entire
`is deposited directly on
`(d} the reactive monomer
`accessible developed surface of the part, both internal and external, and
`polymerized at ambient temperature under a low vacuum, in a method akin to
`the vacuum deposition of a thin metal layer, so as to obtain a continuous
`coating of (substituted or unsubstituted) poly(p-xylylene) of relatively uniform
`thickness, completely (with no discontinuity) covering the part of the medical
`device.
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`10
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`15
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`20
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`25
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`30
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`35
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`Various equipment and corresponding operating procedures are
`nowadays available on the market for the purposes of obtaining a poly(p(cid:173)
`xylylene) coating and, by way of example, reference may be made to the
`equi:pment sold by COMELEC SA, CH-2301 La Chaux de Fonds, Switzerland,
`or alternatively to the PDS 2010 Labcoter 2 equipment sold by SPECIAL TY
`COATING SYSTEMS.
`The coa1ing thus obtained, made of relatively crystalline polymer,
`adheres to the part directly or indirectly. Because of its slip characteristics, the
`coating facilitates the relative movement between the two parts of the medical
`device. In addition, the elastic behaviour of the coating allows it in a resilient
`manner to accommodate the deformations and stresses imposed on the part
`provided with it, for example the piston, as it slides in the container. Thus,
`tightness in the region of contact between the piston and the container can be
`guaranteed to be maintained.
`the part may be direct,
`Adhesion between the coating and
`particularly by means of chemical bonds formed at the time of deposition and
`polymerization of the reactive monomer, between said part and the polymer
`material, or indirect, by way of a tie layer or primer layer applied beforehand to
`the surface that is to be coated, if appropriate after that surface has been
`cleaned or prepared .
`The medical devices as previously defined and discussed therefore
`require substantial improvements, in respect of the following requirements,
`which are sometimes contradictory, as far as the coating is concerned.
`
`Regeneron Exhibit 1008.005
`
`

`

`WO 2009/030976
`
`PCT/IB2007 /O!t3435
`
`4
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`5
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`10
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`15
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`The viscoelastic material of which the piston of a medical device
`such as a syringe tnay be made is generally an elastomeric material which
`alters, in parti?ular degrades chemically over time. This possible degradation is
`sometimes initiated by the processes used to sterilize the medical devices
`containing them, for example bringing them into contact with ionizing radiation .
`Such degradation alters the surface properties of the elastomeric material and
`may cause inadequate interactions with the medical product potentially present
`in the medical device. Such degradation may also affect other surface
`properties of the elastomeric material, for example the adhesion or friction with
`respect to one of the other parts of the medical device. Over time , that is to say
`as soon as the medical device has been filled with the medical product, and in
`parti,cular when it is used or operated, it is therefore necessary for a coating to
`effectively isolate the region of contact between on one hand a first part of the
`device made of such a viscoelastic material and on the other hand the medical
`product or a second part of the device, intended to cooperate with said first
`part, so that the surface characteristics, including the coefficient of friction , of
`the region of contact between the two parts of the medical device, can be
`mairntained over time, even after prolonged storage, regardless from the fact
`that the properties of said viscoelastic material may have been adversely
`affected over time.
`Additionally, it is necessary for such a coating to show surface
`characteristics enabling gliding between the two parts intended to cooperate
`together and also tightness between these two parts at the contact region .
`It is therefore an object of the present invention to provide a
`roughness of coating for at least one part of a medica.l device, said roughness
`allowing on one hand the medical product potentially present in the medical
`device to be preserved and on the other hand to reconcile the gliding function
`between two complementary parts with the maintaining of tightness in the
`contact region of said parts, static tightness over time and dynamic tightness
`30 when using the medical device, whether the coating be provided on a first part
`such as a piston, on a second part such as a container or on an intermediate
`part located between said first and second parts.
`According to the present invention, it has to these ends been found
`that the mean roughness Ra, that is to say the surface finish, of the coating of a
`first coated part in the contact region needs to be equal or less than 2.5 µm,
`
`20
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`25
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`35
`
`Regeneron Exhibit 1008.006
`
`

`

`WO 2009/030976
`
`PCT /IB2UU7 /003435
`
`5
`
`preferably less than 2 µm and more preferably less than 1.5 ~Lm, for example in
`the order of 1.0 µrn.
`Such a roughness is important in giving the coating the desired
`performance and function, independently of the thickness of the coating.
`ln the present application, the roughness Ra is measured according
`the following method
`: roughness measurements done in triplicate are
`performed by using a profiler Wyko NT 1100 (Veeco Instruments Inc. Tucson
`USA) on scans 370 µm x 240 µm with a VS1 mode (Vertical Scanning
`Interferometry) . The calibration of the apparatus is performed following the
`procedure WI 7.6-20 using measuring instruments traceable to the National
`Institute of Standards and Technology (NIST).
`A first aspect of the present invention is a medical device comprising
`at least one first part coated with a coating having a composition comprising at
`least one polymer material comprising polymer chains having the following
`repeat unit:
`
`5
`
`10
`
`15
`
`20
`
`in which X represents a halogen, for example F, or a hydrogen,
`and in which Y1, Y2. Y3, Y4 each independently represent a halogen, for
`example Cl, or a hydrogen,
`characterized in that the outer surface of said coating has a mean
`roughness Ra of less than 2.5 µm.
`The medical device of the invention with at least one part coated
`25 with a coating having sucj1 a roughness allows the medical product intended to
`be present in the medical device to be preserved .
`In embodiments of the invention, said mean roughness Ra is less
`than 2 µm , preferably less than 1.5 µm and, for example, of the order of 1.0
`µm .
`
`30
`
`In embodiments of the invention, said one first part is chosen among
`a piston, the internal surface of a container intended to receive a medical
`
`Regeneron Exhibit 1008.007
`
`

`

`WO 2009/030976
`
`PCT/IB2UU7 /003435
`
`6
`
`product, or an intermediate part located between a piston and the internal
`surface of a container intended to receive a medical product.
`In embodiments of the
`invention , the medical device further
`comprises at least one second part being intended to move relative to said first
`part in a sliding relationship when said medical device is operated, said first
`and second parts defining between them a contact region.
`A roughness Ra· equal or less than 2.5 µm for the outer surface of
`the coating of the medical device of the invention allows a smooth gliding of a
`first coated part, like a piston, relative to a second part, like a container.
`The medical device of the invention allows to have decreased
`activation, sustainable and final forces for moving a first part relative to a
`second part, for example for moving a piston within the container in which it is
`lodged, without having to add a lubricant and while preserving the tightness at
`the contact region between said two parts. For example, in a medical device
`such as a syringe, the piston must be able to be moved relative to the container
`or syringe body, through a gliding movement,. while at the same time ensuring
`the tightness with said container, so that all of the product to be administered
`escapes only via the distal end of the container and does not leak out of said
`container via the piston at the proximal end of the container. The medical
`device of the invention , thanks to a specific coating having a specific roughness
`range at the contact region between the piston and the container, allows the
`successful completion of these two relatively incompatible requirements.
`Moreover, with the medical device of the invention, it is possible to
`decrease the total amount of lubricant, for example silicone oil, that is
`necessary in such a medical device.
`In consequence, the medical device of the invention allows to limit
`the risk of Interaction between a lubricant. for example silicone oil, and the
`therapeutic molecules potentially stored in the container of the medical device
`prior to delivery to a patient.
`In embodiments of the invention, one of said first and second parts
`consists of a viscoelastic material designed to encourage tightness at said
`contact region.
`In embodiments of the invention, said first part is a piston and said
`second part is the internal surface of a container intended to receive a medical
`product or an intermediate part located between said piston and the internal
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`5
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`10
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`15
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`20
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`25
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`30
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`35
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`Regeneron Exhibit 1008.008
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`

`

`WO 2009/030976
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`PCT/IB2UU7 /003435
`
`7
`
`surface of a container intended to receive a medical product, said piston being
`movable within said container when said medical device is operated.
`In embod iments of the invention, said first part is an intermediate
`part foC8ted between a piston and the internal surlace of a container intended
`to receive a medical product, and said second part is a piston or the internal
`surface of a container intended to receive a medical product, said piston being
`movable within said container when said medical devioe is operated.
`In embodiments of the invention, said first part is the internal surface
`of a contalner intended to receive a medical product, and said second part is a
`piston or an intermediate part located between a piston and the internal surface
`of a container intended to receive a medical product, said piston being movable
`within said container when said medical device is operated.
`In embodiments of the invention, said second part is further coated
`with said coating at least in the contact region.
`In embodiments of the invention, said coating is continuous and
`
`elastic.
`
`In embodiments of the invention, said polymer material is chosen
`from the group consisting of poly(p-xylylene), poly(p-meta-chloroxylylene),
`poly(p-ortho-chloro/met~-chloroxylylene) and poly(p-difluoroxylylene).
`For example, said polymer material consists of poly(p-meta-
`chloroxylylene).
`In embodiments of the invention, said coating has a mean thickness
`ranging from 2 to 10 µm, preferably, ranging from 3 to 10 µm, and more
`preferably ranging from 3 to 5 µm.
`Such a thickness has the advantage of ensuring that, regard less of
`the profile, shape or surface characteristics of the coated part, at the end of the
`process of depositing/polymerizing the polymer material, the coating covers the
`entirety of the part over the desired region, namely at least the region
`corresponding to the contact region, with no discontinuity, and does so durably.
`In embodiments of the
`invention, said contact region further
`includes a lubricant other than said coating .
`In embodiments of the invention, said coating provided on said
`container and/or on said piston and/or on said intermediate part is at least
`partially covered with said lubricant.
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`5
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`10
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`15
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`20
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`25
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`30
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`Regeneron Exhibit 1008.009
`
`

`

`WO 2009/030976
`
`PCT/IB2UU7 /003435
`
`8
`
`In embodiments of the invention, said piston or said container or said
`intermediate part, not provided with said coating, is at least partially covered
`with said lubricant.
`In embodiments of the invention, said lubricant contains silicone.
`In embodiments of the invention, the medical device includes an
`injection device.
`A further aspect of the invention is a part for a medical device, the part
`intended to cooperate
`in relative movement with
`respect
`to a
`being
`complementary part in order to operate said medical device, said part
`comprising a coating consisting of at least one polymer material comprising
`polymer chains consisting of the following repeat unit:
`
`in which X represents a halogen, for example F, or a hydrogen,
`and in which Y1, Y2, Y3, Y4 each independently represent a halogen, for
`example Cl, or a hydrogen,
`said coating having a
`outer surface intended to move relative to said
`complementary part,
`characterized in that said outer surface of said coating has a mean roughness
`Ra of less than 2.5 µm.
`Preferably, said outer surface has a mean roughness Ra of less than 2
`µm, preferably less than 1.5 µm and, for example, of the order of 1.0 µm.
`Said coating may be continuous and elastic.
`Preferably, said polymer material is chosen from the group consisting of
`poly(p-xylylene),
`poly(p-meta-chloroxylylene),
`poly(p-ortho-chloro/meta(cid:173)
`chloroxylylene), and poly(p-difluoroxylylene). Preferably, said polymer material
`consists of poly(p-meta-chloroxylene).
`In an embodiment of the invention, the mean thickness of said coating
`ranges from 2 to 10 µm, preferably from 3 to 10 ~Lm, and more preferably from
`3 to 5 µm.
`In an embodiment of the invention, said part comprises at least one of
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`20
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`25
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`Regeneron Exhibit 1008.010
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`

`

`WO 2009/030976
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`PCT/IB2UU7 /003435
`
`9
`
`- a container intended to accommodate a medical product, and/or
`- a piston intended to be moved with respect to said container,
`
`- an intermediate part located between said container and said
`
`and/or
`
`5
`
`piston.
`
`The present invention is now described with reference to the
`attached drawings in which:
`- Figure 1 depicts,. schematically and in cross section, a portion of a
`medical device considered by the present invention and according to a first
`embodiment thereof,
`- Figure 2 depicts, again schematically and in cross section, a
`portion of a medical device according to a second embodiment of the invention.
`With reference to Figures 1 and 2, a medical device 1 considered by
`the present invention, for example a syringe, comprises at least one first coated
`part. As will appear from the description that follows, in figures 1 and 2, the first
`coated part is the piston of a syringe.
`In an embodiment of the invention not shown, the medical device is
`a vial, intended to receive a medical product, and that may be closed by a plug.
`In such a case, the first coated part may be either the plug or the internal
`surface of the vial.
`With reference to figures 1 and 2, the medical device 1 comprises a
`first and a second parts 2 and 3, one being complementary to the other, for
`example a piston 3 housed in a container 2, the piston 3 and the internal
`surface of the container 2 being in contact with one another via a contact region
`10. The piston 3 and the container 2 are ~ble to move one with respect to the
`other in a predetermined gliding movement 4, for example translationally and/or
`rotationally. The container 2 is intended to accommodate a medical product 6 in
`the liquid, gaseous or fluid phase, the volume of said product 6 varying
`according to the movement of the piston 3 with respect to the container 2. In
`particular, for administering the product 6, the piston 3 is caused to move
`distally along arrow 4 of figure 1 in order to push the product 6 out of the
`container 2. The piston 3 is designed to deform in order to tighten the contact
`region 10. For example on figure 2, at least part of the developed surface of the
`piston 3, which corresponds to the contact region 10, is provided with a coating
`8 which is continuous, intrinsically elastic and firmly secured to the piston 3.
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`10
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`35
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`Regeneron Exhibit 1008.011
`
`

`

`WO 2009/030976
`
`PCT /(82007 /003435
`
`10
`
`According to Figure 1, in a first embodiment, the piston 3 comprises
`an intermediate part, under the form of an independent seal 9 housed in a
`groove 11 made in the piston 3, which is made of viscoelastic material, for
`example of elastomer, encouraging deformation of the piston 3 and therefore
`tightening the contact region 10. The seal 9 is also made out of a viscoelastic
`material, for example an elastomer, in order to ensure tightness at the contact
`region 10. With reference to Figure 1, the seal 9 is provided with a coating 8.
`According to Figure 2, in a second embodiment, the piston 3 is made
`in its entirety of a viscoelastic material, for example an elastomer.
`Irrespective of the embodiment considered , the contact region 10
`between the internal surface of the container 2 and the piston 3 also
`determines a region of gliding contact between the piston 3 and the container
`2.
`
`According to the invention, and with reference to Figure 2, the
`internal surface of the container 2 and the piston 3 determine a contact region
`10 which is provided with a coating 8. On the example shown on this figure , the
`coating 8 is provided on the piston 3. According to another embodiment which
`has not been depicted, the coating 8 is provided on the internal surface on the
`container 2. According to other alternative forms of embodiment which have not
`been depicted, the coating 8 may be formed of two individual coatings, one
`provided on the internal surface of the container 2 and one on the piston 3.
`According to another embodiment whiGh has not been depicted, the coating 8
`is provided on one or on the two faces of an intermediate part, such as the seal
`9 shown on figure 1,. located between the piston 3 and the container 2.
`The coating 8 of the medical device 1 of the invention encourages
`the gliding of the piston 3 relative to the container 2 at the time of administration
`of the product 6. Moreover, the coating 8 also ensures static and dynamic
`tightness at the contact region 10 of the two complementary parts, namely the
`piston 3 and the container 2. ln particular, before use of the medical device 1,
`for example during storage, the coating 8 ensures the static tightness between
`the piston 3 and the container 2 by preventing the leakage of the product 6 at
`the contact region 1 O between the piston 3 and the internal surlace of the
`container 2. When the medical device 1 is in use, the coating 8 ensures the
`dynamic tightness between the piston 3 and the internal surface of the
`container 2 by preventing the leakage of the product 6 at the contact region 10
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`Regeneron Exhibit 1008.012
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`

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`WO 2009/030976
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`PCT /IB2UU7 /003435
`
`11
`
`between the piston 3 and the container 2 while the piston 3 is moving relative to
`the container 2.
`According to the invention, the coating 8 consists of at least one
`polymer material comprising polymer chains consisting of the following repeat
`unit:
`
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`in which X represents a halogen, for example F, or a hydrogen, and in which
`Y1, Y2, Y3 and Y 4 each independently represent a halogen, for example Cl, or a
`hydrogen. This coating 8 according to the invention is obtained by diy vacuum
`deposition/polymerization at ambient temperature, as described above.
`The outer surface of the coating 8 has a mean roughness of less
`than 2.5 µm, preferably of less than 2 µm, more preferably of less than 1.5 µm,
`for example of the order of 1.0 µm.
`During the CVP deposition/polymerization process, it is possible to
`control the surface finish, namely the contact or outer surface, of the coating 8.
`For e;x:ample, when coating pistons by the CVP process, the person skilled in
`the art knows that it is possible to control the surface finish, namely the
`roughness obtained, by intermingling the pistons 3 with one another during the
`25 CVP process, on 1:he one hand, and by intermingling them with inserted
`elements (inert parts) mixed in with the pistons 3 while they are being
`intermingled .
`In the present application, the roughness Ra is measured according
`the following method : roughness measurements done in
`triplicate are
`performed by usi,ng a profiler Wyko NT 1100 (Veeco Instruments Inc. Tucson
`USA) on scans 370 µm x 240 µm with a VSI mode (Vertical Scanning
`Interferometry) . The calibration of the apparatus is performed following the
`procedure WI 7 .. 6-20 using measuring instruments traceable to the National
`Institute of Standards and Technology (N IST).
`IJm, measured · as described
`A roughness of less than 2.5
`hereinabove, for the outer surface of a coating 8 of a medical device 1 of 1he
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`Regeneron Exhibit 1008.013
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`WO 2009/030976
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`PCT/IB2UU7 /003435
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`12
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`invention allows a smooth gliding of a such coated part, like a piston 3, relative
`to a complementary part, like a container 2.
`The coating 8 according to the invention has for example a thickness
`ranging from 2 to 10 µm. Hence, when the contact region 10 is provided with
`two individual coatings 8, one provided on the internal surface of the container
`2 and one on the piston 3, the thickness of the coating 8 of the medical device
`will therefore be the sum of the thicknesses of each individual coating 8.
`Starting with
`the appropriate dimer, and using equipment as
`identified hereinabove, the person skilled in the art will know how to deposit
`and control a predetermined thickness of the polymer material adopted,
`particularly by varying the time for which the part that is to be coated is
`exposed to
`the reactive monomer form of the poly(p-xylylene) chosen.
`Furthermore, a person skilled in the art knows that the rate of deposition/
`polymerization is directly proportional to the square of the reactive monomer
`concentration , and inversely proportional to the absolute temperature of the
`part exposed to the monomer, this infonnation allowing him to modify and
`control the thickness of the coating deposited on the part.
`The present invention considers various substrates or viscoelastic
`materials to be appropriate to the deposition of a coating 8 as previously
`defined, these being various natural or synthetic elastomers: silicones, nitrile(cid:173)
`based elastomers, natural or synthetic rubber,
`fluorocarbon elastomers,
`polyurethanes. As a preference, the invention will devote itself to bromobutyl
`and chlorobutyl synthetic elastomers.
`By way of example, the mean thickness of the coating 8 ranges from
`2 to 10 µm and preferably from 3 to 10 µrn and, more preferably still, from 3 to
`5 ~tm.
`
`Such a specific thickness range allows a smooth gliding of two
`complementary parts relative to each other while ensuring tightness at the
`contact region between said two complementary parts.
`As stated above, the polymer material is preferably chosen from the
`group consisting of poly(p-xylylene), poly(p-meta-chloroxylylene), poly(p-ortho(cid:173)
`chloro/meta-chloroxylylene) and poly(p-difluoroxylylene). As a preference, the
`polymer material consists of poly(p~meta~chloroxylylene).
`By implementing the invention, it is possible, to a significant extent,
`to limit or even eliminate the amount of lubricant other than the aforementioned
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`WO 2009/030976
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`PCT/IB2UU7 /003435
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`polymer material, for example silicone oil, customarily used at the contact
`region 10 of sliding contact between the piston 3 and the container 2.
`The present invention will now be illustrated with the following
`examples.
`
`Example 1 :
`
`The following test protocol is performed on a medical device 1 of the
`syringe type, according to the second embodiment depicted in Figure 2 of the
`present application.
`The container 2 is a glass syringe body accommodating a piston 3
`able to move translationally along arrow 4 of figure 2 inside the container 2.
`The piston 3 is made of a viscoelastic material such as bromobutyl rubber
`commercially available at West Company, or chlorobutyl rubber commercially
`available at West Company.
`Various medical devices, or container-piston systems, were tested :
`some with non coated pistons, others with coated pistons. The coated pistons 3
`were coated with a coating 8 as previously defined, in which the polymer
`material is poly(p-meta-chloroxylylene) (Parylene C). Regarding the coated
`pistons, several surface fin ishes or roughnesses of the outer surface of coating
`8 were tested , as summarized in Table 1 below.
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`Regeneron Exhibit 1008.015
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`WO 2009/030976
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`PCT/IB2UU7 /003435
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`Table 1 : configurations of pistons A, 81 and C
`
`14
`
`Piston reference
`
`Viscoela:.lio substrate
`
`Coating
`
`Coating
`
`Surface finish
`
`Bromobutyl rubbe.-
`
`No
`
`thrckness
`-
`
`Smooth
`
`Ra"'0.7µm
`
`Rt = 11.4 µm
`
`Bromobutyt fUbber
`
`Yes
`
`3µm
`
`Smooth
`
`Ra= 0.9µm
`
`Rt =12.0µm
`
`Bromobutyl rubber
`
`Yes
`
`3µm
`
`Rough
`
`A
`
`(comparative)
`
`81
`
`(invention)
`
`62
`
`(