PCT
`
`WORLD INTELLECTUAL PROPERTY ORGANIZATION
`Intematronal Bureau
`
`
`
`
`INTERNATIONAL APPLICATION PUBLISHED UNDER THE PATENT COOPERATION TREATY (PCT)
`
`(51) International Patent Classification 6 :
`
`(1]) International Publication Number:
`
`WO 99/38554
`
`A61M 5/315, 5/24
`
`(43) International Publication Date:
`
`5 August 1999 (05.08.99)
`
`(21) International Application Number:
`
`PCT/DK99/00042
`
`(22) International Filing Date:
`
`(30) Priority Data:
`PA 1998 00130
`
`30 January 1998 (30.01.98)
`
`DK
`
`(71) Applicant: NOVO NORDISK A/S [DK/DK]; Novo Alle,
`DK—2880 Bagsvaerd (DK).
`
`STEENFELDT—JENSEN, Saren; Holmevaenget
`(72) Inventors:
`2B, DK—3100 Hombaek (DK). HANSEN, Steffen; Gl.
`Frederiksborgvej 64A, DK~3400 Hillerad (DK).
`
`(74) Agent: NOVO NORDISK A/S; Corporate Patents, Novo Alle,
`DK—2880 Bagsvaerd (DK).
`
`28 January 1999 (28.01.99)
`
`
`
`(81) Designated States: AL, AM, AT, AU, AZ, BA, BB, BG, BR,
`BY, CA, CH, CN, CU, CZ, DE, DK, EE, ES, FI, GB, GD,
`GE, GH, GM, HR, HU, ID, IL, IN, IS, JP, KE, KG, KP,
`KR, KZ, LC, LK, LR, LS, LT, LU, LV, MD, MG, MK,
`MN, MW, MX, NO, NZ, PL, PT, RO, RU, SD, SE, 56,
`
`SI, SK, SL, TJ, TM, TR, Tr, UA, UG, UZ, VN, YU, ZW,
`ARIPO patent (GH, GM, KE, LS, MW, SD, 52, UG, ZW),
`Eurasian patent (AM, AZ, BY, KG, KZ, MD, RU, TJ, TM),
`European patent (AT, BE, CH, CY, DE, DK, ES, FI, FR,
`GB, GR, IE, IT, LU, MC, NL, PT, SE), OAPI patent (BF,
`BJ, CF, CG, CI, CM, GA, GN, GW, ML, MR, NE, SN,
`TD, TG).
`
`Published
`With international search report.
`Before the expiration of the time limit for amending the
`claims and to be republished in the event of the receipt of
`amendments.
`
`
`
`(54) Title: AN INJECTION SYRINGE
`
`(57) Abstract
`
`In an injection syringe comprising a housing (1), a piston rod (6) with a not circular cross section and an
`
`outer thread (7), a piston rod drive comprising a piston rod guide (85) mating the cross section of the piston rod
`
`(6) and a nut (4) which is not axially displaceable and mates the thread (7) of the piston rod (6) to form a self
`
`locking thread connection, and a dose setting mechanism comprising a not self locking thread connection along
`
`which an injection button by rotation of a dose setting element (81) is screwed out to project from the housing
`
`(1) and which thread connection by axial returning of the injection button (88) transforms this axial movement
`
`into a rotation of one of the piston drive elements (85) relative to the other one (4). A unidirectional coupling
`
`between the nut member (4) and the piston rod guide (85) allows rotation in one direction by which the piston
`rod (6) is transported in a distal direction. The coupling has an initial reluctance to be overcome before rotation
`
`
`takes place said reluctance being large enough to resist torques exerted during the dose setting.
`
`
`
`Sanofi Exhibit 2015.001
`
`Mylan v. Sanofi
`lPR2018-01676
`
`Sanofi Exhibit 2015.001
`Mylan v. Sanofi
`IPR2018-01676
`
`

`

`Codes used to identify States party to the PCT on the front pages of pamphlets publishing international applications under the PCT.
`Albania
`LS
`ES
`Lesotho
`SI
`Slovenia
`Fl
`LT
`Armenia
`Lithuania
`SK
`Slovakia
`Austria
`FR
`LU
`SN
`Luxembourg
`Senegal
`Australia
`GA
`LV
`Latvia
`SZ
`Swaziland
`GE
`MC
`Monaco
`TD
`Chad
`Azerbaijan
`GE
`MD
`TG
`Bosnia and Herzegovina
`Republic of Moldova
`Togo
`Barbados
`GH
`MG
`TJ
`Madagascar
`Tajikistan
`MK
`GN
`TM
`Turkmenistan
`Belgium
`The former Yugoslav
`Burkina Faso
`GR
`TR
`Turkey
`Republic of Macedonia
`HU
`TT
`Mali
`Bulgaria
`Trinidad and Tobago
`Benin
`[E
`UA
`Ukraine
`Mongolia
`Brazil
`[L
`Mauritania
`UG
`Uganda
`Belarus
`[S
`Malawi
`US
`United States of America
`IT
`Canada
`Mexico
`UZ
`Uzbekistan
`VN
`Viet Nam
`JP
`Central African Republic
`Niger
`KE
`V U
`Netherlands
`Congo
`Yugoslavia
`Switzerland
`KG
`ZW
`Zimbabwe
`Norway
`KP
`cote d’Ivoire
`New Zealand
`Cameroon
`Poland
`China
`Portugal
`Cuba
`Romania
`Russian Federation
`Czech Republic
`Sudan
`Germany
`Denmark
`Sweden
`Estonia
`Singapore
`
`Spain
`Finland
`France
`Gabon
`United Kingdom
`Georgia
`Ghana
`Guinea
`Greece
`Hungary
`Ireland
`Israel
`Iceland
`Italy
`Japan
`Kenya
`Kyrgyzstan
`Democratic People’s
`Republic of Korea
`Republic of Korea
`Kazakstan
`Saint Lucia
`Liechtenstein
`Sri Lanka
`Liberia
`
`KR
`KZ
`LC
`Ll
`LK
`LR
`
`ML
`MN
`MR
`MW
`MX
`NE
`NL
`NO
`NZ
`PL
`PT
`RO
`RU
`SD
`SE
`SG
`
`
`
`
`
`FOR THE PURPOSES OI" INFORMATION ONLY
`
`
`
`AL
`AM
`AT
`AU
`AZ
`BA
`BB
`BE
`BF
`BC
`BJ
`BR
`BY
`CA
`CF
`CG
`CH
`CI
`CM
`CM
`CU
`CZ
`DE
`DK
`EE
`
`
`
`
`Sanofi Exhibit 2015.002
`
`Mylan v. Sanofi
`lPR2018-01676
`
`Sanofi Exhibit 2015.002
`Mylan v. Sanofi
`IPR2018-01676
`
`

`

`WO 99/38554
`
`PCT/DK99/00042 _
`
`Anin’
`
`ins rin e
`
`The invention relates to injection syringes of the kind apportioning set doses of a medicine
`
`from a cartridge containing an amount of medicine sufficient for the preparation of a number
`
`of therapeutic doses.
`
`Such syringes are mainly made for users who have to inject themselves frequently, e. g.
`
`diabetics. A number of demands are set to such syringes. The setting of a dose must be
`
`easy an unambiguous and it must be easy to read the set dose. It must be possible with a
`
`minimum of trouble to cancel or change a Wrongly set dose and when the dose is injected
`
`the dose setting must return to zero. When a disposable syringe is in question, Le, a syringe
`
`which is disposed of when the cartridge is empty, the syringe must further be cheap and
`
`made of materials suited for recycling or burning without producing noxious gases. For these
`
`purposes the number of parts from‘which the syringe is constructed and the number of dif-
`
`ferent kinds of materials used in the syringe should be kept at a minimum.
`
`Most dose setting devices work with a threaded piston rod co-operating with a nut where the
`
`nut and the piston rod may be rotated relative to each other. The dose setting may be ob-
`
`tained by screwing the nut away from a stop to which it is returned during the injection by
`
`pressing the piston rod until the nut member abuts the stop. By other dose setting devices
`
`one of the elements, the nut or the piston rod, is kept inrotatable and the other is allowed to
`
`rotate a set angle depending on the set dose, whereby the piston rod is screwed a distance
`
`through the nut.
`
`in most syringes for apportioning set doses it is preferred that the piston rod is backing up
`
`the piston upon which it works during the injection. To obtain this precaution is taken to pre-
`
`vent the piston rod from moving in a proximal direction.
`
`The syringe according to EP 327 910 is of the type wherein a nut is screwed away from a
`
`stop. During the setting of the dose the screwing may be performed in both direction so that
`
`a too large set dose may be lowered just by rotating the nut in an opposite direction. Means
`
`are provided preventing that negative doses are set. The mutual rotation of the piston rod
`
`and the nut is obtained by rotating a cap relative to the pen housing and a set dose may be
`
`10
`
`15
`
`20
`
`25
`
`30
`
`Sanofi Exhibit 2015.003
`
`Mylan v. Sanofi
`lPR2018-01676
`
`Sanofi Exhibit 2015.003
`Mylan v. Sanofi
`IPR2018-01676
`
`

`

`WO 99/38554
`
`PCT/DK99/00042
`
`2
`
`read on a scale and a pointer provided at adjacent edges of the housing and the cap, these
`edges being so shaped that the cap can only be mounted firmly on the housing when the
`pointer points zero on the scale. It may be seen as a weak point that doses larger than the
`one obtained by rotating the parts 360° must be calculated by adding the number pointed at
`on the scale and a number printed on the side of a tubular extension of the nut which is
`
`moved out from the proximal end of the housing proportionally with the dose set and which
`tubular extension is closed at its proximal end to form an injection button.
`
`In EP 450 905 the above drawback is overcome by writing the numbers along a helical line
`on a tubular extension of the nut so that these number may successively be seen in a win-
`dow in a housing element enclosing said tubular extension. Hereby the size of the dose is
`indicated unambiguously but the user have to remember to set the dose setting device on
`zero before the next setting of a dose is performed. If this is forgotten a wrong dose may be
`set and the number may not be seen clearly in the window.
`
`In EP 608 343 is described a pen having a dose setting mechanism wherein the dose is set
`by rotating 8 button relative to a housing to set a dose. By the rotation the button is screwed
`up from the end of the housing in a thread having a pitch so large that the thread connection
`is not self blocking, i. e. when the button is presses back to the end of the housing it will ro-
`tate back in the thread. The button is through a ratchet coupled to a driver, the ratchet form-
`ing a unidirectional coupling which during the rotation of the button in one direction to set a
`dose rides or clicks over the teeth of the ratchet. The cylindrical side of the button carries
`numbers which shows the size of the set dose in a window when the button is screwed out-
`ward. When the button is screwed back the unidirectional coupling will transmit the rotation
`to the driver which has a nut co-operating with a threaded piston rod which is made inro-
`tatable in a housing . This thread connection has a pitch which makes the nut self locking on
`the piston rod. A set dose may be cancelled by drawing the engaging parts of the ratchet out
`of engagement against the force of a spring so that the rotation of the button is not trans-
`mitted to the driver and then press the button back to the housing . This pen fulfils all the
`objects mentioned only the dose cancelling procedure is a little troublesome as the close set
`button cannot as it will come most naturally just be screwed back if a too large dose is set.
`Concomitantly forcing the coupling parts apart against the force of the spring and pressing or
`screwing the button back may be a little difficult and the demand for a spring necessitates
`use of metal parts in the syringe,
`
`10
`
`15
`
`20
`
`25
`
`30
`
`Sanofi Exhibit 2015.004
`
`Mylan v. Sanofi
`lPR2018-01676
`
`Sanofi Exhibit 2015.004
`Mylan v. Sanofi
`IPR2018-01676
`
`

`

`WO 99/38554
`
`PCT/DK99/00042
`
`It is an object of the invention to provide a syringe which has the mentioned advantageous
`features without having the drawbacks known from existing syringes.
`
`This is obtained by an injection syringes for apportioning set doses of a medicine from a
`cartridge containing an amount of medicine sufficient for the preparation of a number of
`therapeutic doses, comprising
`
`a housing
`
`a piston rod having a not circular cross~section and an outer thread
`
`a piston rod drive comprising two elements
`
`5
`
`10
`
`15
`
`a piston rod guide in relation to which the piston rod is axially displaceable but not
`a)
`rotatable, and
`
`a nut member which is rotatable but not axially displaceable in the housing and
`b)
`which has an inner thread mating the thread of the piston rod to form a self locking thread
`connection,
`
`20
`
`25
`
`30
`
`a dose setting mechanism comprising a not self locking thread connection along which an
`injection button by rotation of a dose setting element relative to said housing is screwed out
`from the proximal end of the housing to project from this proximal end a distance deter—
`mined by the angle of said rotation and which thread connection by axial returning of the in-
`jection button transforms this axial movement to a rotation of one of the piston drive ele-
`ments relative to the other,
`'
`
`which syringe according to the invention is characterised in that
`
`a unidirectional coupling is provided between the nut member and the piston rod guide al-
`lowing rotation of these parts relative to each other in one direction but not in the opposite
`direction, the allowed rotation being one by which the piston rod is transported in a distal di-
`
`Sanofi Exhibit 2015.005
`
`Mylan v. Sanofi
`lPR2018-01676
`
`Sanofi Exhibit 2015.005
`Mylan v. Sanofi
`IPR2018-01676
`
`

`

`WO 99/38554
`
`PCT/DK99/00042
`
`not inadvertently altered. The clicks may be taken as an audible signal indicating the size of
`
`the set dose.
`
`Sanofi Exhibit 2015.006-
`Mylan v. Sanofi
`lPR2018-01676
`
`Sanofi Exhibit 2015.006
`Mylan v. Sanofi
`IPR2018-01676
`
`

`

`WO 99/38554
`
`PCT/DK99/00042
`
`Sanofi Exhibit 2015.007
`
`Mylan v. Sanofi
`lPR2018-01676
`
`Sanofi Exhibit 2015.007
`Mylan v. Sanofi
`IPR2018-01676
`
`

`

`WO 99/38554
`
`PCT/DK99/00042
`
`formed into a rotation.
`
`5
`
`In an appropriate embodiment of the syringe according to the invention the dose scale drum
`is mounted rotatable but not axially displaceable on the injection button.
`
`10
`
`20
`
`25
`
`turned to its zero posmon when the button is pressed home When rotation of the dose
`scale drum and the piston rod is induced by the ax1al movement of the Injection button this
`button is reacted upon by a torque which must be taken up by the click connection between
`the injection button and the housing which connection must consequently be strong enough
`to absorb this force without rotating.
`
`30
`
`the invention,
`
`Figure 2 shows a sectional view along the line ll-ll in figure 1,
`
`Figure 3 shows in a reduced scale an exploded view of the syringe in figure 1,
`
`Sanofi Exhibit 2015.008
`
`Mylan v. Sanofi
`lPR2018-01676
`
`Sanofi Exhibit 2015.008
`Mylan v. Sanofi
`IPR2018-01676
`
`

`

`WO 99/38554
`
`7
`
`PCT/DK99/00042
`
`Figure 4
`
`shows a sectional view along the line lV—lV in figure 1,
`
`Figure 5
`
`5
`
`Figure 6
`
`shows a sectional view along the line V-V in figure 1,
`
`shows a front view of another embodiment of an syringe according to the
`invention,
`
`10
`
`Figure 7
`
`shows a sectional view along the line Vll-Vll in figure 6,
`'
`_
`Figure 8 shows in a reduced scale an exploded view of the syringe in figure 6,
`
`Figure 9 shows a sectional view along the line lX-lX in figure 6,
`
`15
`
`Figure 10
`
`shows a sectional view along the line X-X in figure 6.
`
`Figure 11
`
`shows a sectional side view of another embodiment of a syringe according
`
`to the invention,
`
`20
`
`Figure 12
`
`shows a sectional side view perpendicular to the view in figure 11,
`
`Figure 13
`
`shows in a reduced scale an exploded view of the syringe in figure 11 and
`12,
`
`25
`
`Figure 14
`
`shows a sectional side view of the dose setting part of another embodiment
`of a syringe according to the invention,
`
`Figure 15
`
`shows a sectional side view of still another embodiment of a syringe ac-
`cording to the invention,
`
`30
`
`Figure 16
`
`shows a sectional side view perpendicular to the view in figure 15,
`
`Figure 17
`
`shows in a reduced scale an exploded view of the syringe in figure 15 and
`16,
`
`Sanofi Exhibit 2015.009
`
`Mylan v. Sanofi
`lPR2018-01676
`
`Sanofi Exhibit 2015.009
`Mylan v. Sanofi
`IPR2018-01676
`
`

`

`WO 99/38554
`
`PCT/DK99/00042
`
`10
`
`15
`
`20
`
`25
`
`30
`
`Sanofi Exhibit 2015.010
`
`Mylan v. Sanofi
`lPR2018-01676
`
`Sanofi Exhibit 2015.010
`Mylan v. Sanofi
`IPR2018-01676
`
`

`

`WO 99/38554
`
`PCT/DK99/00042
`
`10
`
`15
`
`20
`
`25
`
`30
`
`just mentioned. The pitch angle of the threads exceeds the angle of friction for the materials
`forming the parts of the thread connection and consequently the thread connection is of the
`not self locking type which induce a relative rotation of the parts of the connection when
`these part are moved axially relative to each other.
`
`Numbers indicating set doses are printed on the outer wall of the dose drum 17 and the
`number corresponding to a set dose is shown in a window 18 provided in the side wall of the
`housing 1.
`
`proximal end of the syringe. Said end of the extension is closed by an end wall 19 having a
`central outer protrusion 20. ln a part of the wall adjacent to the end wall 19 the extension 21
`is provided with slots 22. The said end of the extension is covered by a cup shaped cap 23
`forming an injection button. Internal hooks 24 at the open end of this cap snaps over an ex-
`ternal circumferential bead 25 on the extension 21 and the protrusion 20 on the end wall 19
`abuts the inner side of the bottom of the cap 23 to form a journal about which the injection
`button can rotate relative to the extension 21 whereas it cannot be axially displaced relative
`to this extension.
`
`A driver tube 26 integral with the piston rod guide 14 extends from this piston rod guide to
`the end wall 19 of the dose scale drum extension 21 and is at its proximal end divided into
`tongues 27 terminated by external hooks 28 engaging the slots 22 in the extension 21. This
`way the dose scale drum 17 is bound to rotate with the driver tube 26 but is axially displace-
`able relative to this tube.
`
`To set a dose the ampoule holder 2 is rotated anticlockwise in the first division of the hous-
`ing 1. This rotation is performed against a resistance presented due to the fact that a protru-
`sion 30 on the outer wall of the ampoule holder rests in one of a number of depressions 31
`
`Sanofi Exhibit 2015.011
`
`Mylan v. Sanofi
`lPR2018-01676
`
`Sanofi Exhibit 2015.011
`Mylan v. Sanofi
`IPR2018-01676
`
`

`

`WO 99/38554
`
`PCT/DK99/00042
`
`10
`
`circumferentially provided in the inner wall of said first division of the housing as shown in the
`cross-sectional view in figure 3. The angular spacing of the depressions are appropriately
`made so that a dose of one unit is set when the protrusion is moved from one depression to
`the neighbouring depression so that the number of clicks heard and felt during the dose set-
`ting rotation corresponds to the size of the set dose.
`
`The rotation of the ampoule holder is due to the friction in the engaging threads 5 and 7
`
`1O
`
`15
`
`2O
`
`25
`
`30
`
`protrusion 29 at its end engaging the pawl wheel teeth 10 and by providing depressions 32 in
`the ramp shaped edges 12 of the pawl wheel
`teeth into which depressions the protrusion
`29 on the pawl 13 will rest. Before the clicking release of the coupling is obtained a torque
`sufficient to lift up‘the protrusion 29 of the pawl 13 from the depression 32 in the ramp
`shaped edge 12 must be provided. Altogether a moderate torque can be transmitted from
`the rotated ampoule holder 2 to the driver tube 26. As the hooks 28 at the proximal end of
`the driver tube 26 engage the slots 22 in the dose scale drum extension 21 the dose scale
`drum will be rotated and be screwed upwards in the second division of the housing 1 and the
`injection button 23 will be lifted to protrude from the proximal end of the housing 1. As only a
`small torque is needed to screw up the dose scale drum this is obtained without releasing
`the unidirectional coupling to its clicking release function mode. The size of the set dose can
`currently be seen on the part of the dose scale drum which is presented in the window 18. If
`a too large dose has been set the ampoule holder can be rotated in a clockwise direction
`until the number corresponding to the size of the wanted doe is presented in the window 18.
`
`To inject the set dose the injection button 23 is pressed home into the housing 1. Thereby
`the dose scale drum 17 is pressed in the distal direction and due to the thread connection
`between said drum and the housing 1 a torque is exerted on the drum rotating this drum in a
`clockwise direction. Said torque is via the slots 22 in the drum extension 21 and the hooks
`28 at the end of the driver tube 26 and this tube itself transmitted to the piston rod guide 14.
`The pawls 13 on the piston rod guide are allowed to rotate in the clockwise direction when
`the torque is strong enough to overcome the reluctance provided by the protrusions 29 on
`the pawls engaging the depressions 32 in the ramp shaped edges of the pawl wheel teeth.
`
`Sanofi Exhibit 2015.012
`
`Mylan v. Sanofi
`lPR2018-01676
`
`Sanofi Exhibit 2015.012
`Mylan v. Sanofi
`IPR2018-01676
`
`

`

`WO 99/38554
`
`‘
`
`11
`
`PCT/DK99/00042
`
`Such a strong torque is provided if only the inject button 23 is pressed hard enough. The
`piston rod guide 14 will now rotate clockwise with the unidirectional coupling working in its
`clicking released mode and the piston rod will be rotated clockwise too and will thereby be
`screwed through the wall 4 further into the ampoule accommodating compartment 8. The
`unidirectional coupling will never allow an anticlockwise rotation of the piston rod guide and
`the piston and this way it is ensured that the pressure foot 9 will never be drawn out of
`
`abutment with the piston in a not shown ampoule in the compartment 8.
`
`in the shown embodiment the end wall 4 with its threaded bore forms a nut member relative
`
`to which the piston rod is rotated by the piston rod guide 14 and the driver tube 26. Embodi-
`ments may be‘imagined wherein the piston rod guide is provided in the wall 4 and a nut ele-
`ment is rotated by the driver tube and such embodiment will not be beyond the scope of the
`invenfion.
`
`Another embodiment is described with reference to the figures 6-10. Ele‘ments correspond-
`ing to elements in the embodiment described with references to the figures 1-5 are provided
`with the same reference numbers. Different from the embodiment in figure 1-5 is the fact that
`the injection button 23 and not the dose scale drum 17 is provided with an extension 33, and
`that the driver tube 26 is omitted. Further the injection button 23 is provided with a flange 32
`which abuts the end of the housing when the injection button is pressed home. The exten-
`sion 33 serves as a journal for the dose scale drum 17 which is free to rotate on this journal
`but bound to follow axial movements of the injection button 23 due to hooks 34 at the end of
`the extension 33. A longitudinal bore 35 in the injection button and its extension 33 is pro-
`vided with an internal helical rib 36 engaging a corresponding helical groove in an enlarge-
`ment 37 at the proximal end of the piston rod to form a thread connection between said but-
`ton 23 and said piston rod 6. The pitch of this thread connection is so that a not self locking
`thread connection is formed.
`‘
`
`To set a dose the injection button 23 is manually rotated in a clockwise direction Thereby
`this button is screwed outwards from the housing 1 as the piston rod 6 will through the piston
`rod guide 14 and the unidrectional coupling be kept inrotatable although said unidirectional
`coupling in influenced by a torque in its release direction, however, due to the provided initial
`reluctance the piston rod guide 14 will not immediately be rotatable. In its movement out-
`
`wards the injection button 23 will draw the dose scale drum 17 with it. When this drum is
`
`10
`
`15
`
`20
`
`25
`
`30
`
`Sanofi Exhibit 2015.013
`
`Mylan v. Sanofi
`lPR2018-01676
`
`Sanofi Exhibit 2015.013
`Mylan v. Sanofi
`IPR2018-01676
`
`

`

`WO 99/38554
`
`PCT/DK99/00042
`
`1 2
`
`moved axially in the housing it will be rotated due to the not self locking thread connection
`between said drum 17 and the housing 1.
`
`By this construction the thread along which the injection button is screwed outwards and the
`tread along which the dose scale drum is rotated in the housing may be different.
`
`A click connection corresponding to the one established between the cartridge holder 2 and
`the housing 1 in the embodiment according to figure 1 is in the embodiment according to fig-
`ure 6 appropriately provided between the injection button 23 and the housing 1 where one or
`more protrusions 38 provided on the inner wall of the housing engages grooves 39in a cylin-
`drical outer wall of the button 23. Thereby axial movement of the injection button is allowed
`in all its possible angular positions.
`
`When the injection button is pressed to inject a set dose said button will be maintained inro-
`tatable during its axial movement as the locking between the above mentioned protrusions
`on the inner wall of the housing and grooves on the outer wall of the button is strong enough
`to absorb the torque exerted on the injection button when it drives the piston rod to rotation
`in a clockwise direction after having overcome the reluctance against rotation in the release
`direction of the unidirectional coupling.
`
`The embodiment shown in figure 11, 12 and 13 has the housing 1 with the window 18. The
`end wall 4 with the internal thread 5 is provided in a separate member 40 which is mounted
`in an end of the housing, the member 40 having protrusions 41 engaging slots 42 in the
`housing to lock the member 40 to the housing 1. Further the member 40 has at its periphery
`longitudinal recesses 43 which are engaged by not shown internal ribs in the housing to lock
`the member 40 against rotation relative to the housing 1. Further protrusions 44 on the am-
`poule holder 2 engage the slots 42 to lock the ampoule holder 2 to the housing 1.
`
`The piston rod 6 engages by its external thread 7 the internal thread of the end wall 4 and is
`at its end in the ampoule holder terminated by a pressure foot 9 relative to which the piston
`rod 6 is rotatable. A driver tube 45 is at one end provided with the pawl 13 which engages
`pawl wheel teeth in the member 40 and is held between a ring shaped wall 46 in the housing
`and the end wall 4 in the member 40 to keep the driver tube 45 from axial movement but al-
`lowing it to rotate. On its inner wall the driver tube 45 has a key engaging a longitudinal re-
`
`1O
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`15
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`20
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`25
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`30
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`Sanofi Exhibit 2015.014
`
`Mylan v. Sanofi
`lPR2018-01676
`
`Sanofi Exhibit 2015.014
`Mylan v. Sanofi
`IPR2018-01676
`
`

`

`WO 99/38554
`
`PCT/DK99/00042
`
`1O
`
`15
`
`20
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`25
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`30
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`In the proximal end of the housing 1 a bushing 53 is secured to be non rotatable an non dis-
`placeable relative to said housing 1 the rotational locking being obtained by lugs 54 at the
`proximal end of the housing engaging recesses 55 at the periphery of the bushing 53. A
`guide member 56 is longitudinally displaceable in the bushing 53 but inrotatable relative to
`said bushing and consequently relative to the housing 1. The guide member has at its distal
`end an annular end wall 57. The part 51 of the nut member 48 is passed through the open-
`ing of said end wall 57 and has a bead 58 gripping into a circuferential inner recess in the
`wall of annular opening through said end wall to keep the bushing 53 secured to said part 51
`so that this part can be rotated but not axially displaced in relation to the bushing 53. The
`scale drum 17 is journalled on the nut member 48 and is held on this nut member by having
`a flange 90 held between the end wall 57 of the guide member 56 and the shoulder formed
`where the part 51 connects to the nut member 48.
`
`The button 23 is held rotatably on the guide member 56 which has a ring bead 59 engaging
`a circumferential recess 60 in the inner wall of the button 23 which recess 60 is somewhat
`broader than than the bead 59 so that the button in excess of being rotatable on said bush-
`ing 53 can be axially displaced a distance defined by the width of the recess 60 relative to
`the width of the bead 59. The button 23 is coupled to the nut member 48 by internal ribs 61
`in the tubular part 52 engaging slots 62 in the proximal part of the part 51 of the nut member
`48. This coupling forces the button 23 and the nut member 48 to follow each other in rota-
`tional movements but allow a minor relative axial displacement.
`
`The proximal end surface of the guide member 56 has one or more axially directed protru-
`sions 63 which can co-operate with radial recesses 64 in the bottom of the button 23, but
`mainly a biasing keeps these recesses and protrusions out of engagement. Further the
`guide member has at its proximal end at least one radial protrusion 65 which is biased to en-
`gage axiai recesses 66 in an inner wall of the button to produced a click sound each time the
`
`Sanofi Exhibit 2015.015
`
`Mylan v. Sanofi
`IPR2018-01676
`
`Sanofi Exhibit 2015.015
`Mylan v. Sanofi
`IPR2018-01676
`
`

`

`WO 99/38554
`
`PCT/DK99/00042
`
`14
`
`button is rotated relative to the bushing so that the protrusion jump from one recess to the
`neighbour recess.
`
`To set a dose the button 23 is rotated in a clockwise direction. This rotation is due to the
`coupling between the ribs 61 and the slots 62 transmitted to the nut member 48 which is
`
`then screwed in distal direction along the driver tube 45 which is held inrotatably in the
`housing due to the reluctans of the pawl 13 to move along the pawl teeth in the member 40.
`The movement of the nut member 48 in proximal direction makes the scale drum 17, the
`guide member 56, and the tubular part 52 with the button move in proximal direction so that
`the button is elevated over the end proximal end of the housing 1. A to high set dose can be
`reduced by rotating the button in an anti clockwise direction.
`
`During the rotation of the button the radial protrusion 65 of the guide member 56 clicks from
`
`one axial recess 66 to the other. The distance between can appropriately be chosen so that
`a click corresponds to a changing of the set dose by one international unit up or down. Due
`to engagement between the helical grove on the cylinder wall of the scale drum and a helical
`
`rib on the inner wall of the housing the movement of the dose scale drum 17 will rotate and
`
`displace said drum so that the set dose is shown in the window 18.
`
`When the dose scale drum is displaced outwardly in the housing a steep front side of a saw
`tooth 91 at the proximal end of the dose scale drum 18 will abut a steep front side of a simi-
`lar tooth 92 on the bushing whereby the rotation of the dose scale drum is stopped to indi-
`cate that a maximum dose has been set.
`
`To inject the set dose the button 23 is pressed. Thereby the bias keeping the protrusions 63
`and the recesses 64 out of engagement is overcome and the said engagement is estab-
`lished. The button 23 is now locked relative to the guide element 56 which is again locked
`against rotation relative to the bushing 53 and consequently relative to the housing 1. The
`coupling between the tubular part 52 and the nut member 48 makes this nut member inro-
`
`tatable relative to the housing so an axial movement of said nut member in a distal direction
`
`will due to the not self locking thread coupling between this nut element and the driver tube
`
`45 make this driver tube 45 rotate in a clockwise direction and due to the key/groove cou—
`pling between the driver tube 45 and the piston rod 6 said piston rod will be screwed through
`the end wall 4 further into the ampoule holder compartment. The locking of the button 23
`
`1O
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`15
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`20
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`25
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`30
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`Sanofi Exhibit 2015.016
`
`Mylan v. Sanofi
`lPR2018-01676
`
`Sanofi Exhibit 2015.016
`Mylan v. Sanofi
`IPR2018-01676
`
`

`

`WO 99/38554
`
`PCT/DK99/00042
`
`15
`
`against rotation during the injection ensures that the set dose is not inadvertently changed .
`during the injection.
`
`In the embodiment shown in figure 14 separate buttons are provided for the dose setting and
`the injection. Corresponding to previously described embodiments this one has a housing 1
`and a driver tube 67 which is rotatable in only one direction due to a pawl which engage pawl
`wheel teeth in a part secured in the distal end of the housing. Trapping of the pawl between
`the member 40 and a ring shaped wall 46 in the housing fixes the driver tube against axial
`movement. On the outer wall of the driver tube 67 an axial rib 68 is provided which rib en-
`gages an axial recess 69 in a tubular injection element 70 to transmit rotation of said injec-
`tion element to the driver tube 67.
`
`At the proximal end of the housing 1 a dose setting button 71 is mounted so that this button
`can be rotated but not axially displaced relative to the housing 1. This is obtained by the fact
`that the dose setting button 71 on a part fitting into the housing has a ring shaped bead 72
`which engages a mating circuferential recess 73 in the inner wall of the housing. Outside the
`housing the dose setting button has a part having a diameter corresponding to or being
`larger than the diameter of said housing which part can be provided with axial ribs 74 to en-
`sure a good grip by the setting of a dose. The dose setting button 71 has a central bore the
`inner wall of which has a helical recess 75 engaging a helical rib 76 provided on the outer
`wall of the proximal part of the injection element 70 which element passes through the bore
`of the dose setting button 71. The outer wall of the distal part of the injection element 70
`forms a journal for the scale drum 17 which through an outer helical recess engaged by an
`internal helical rib 16 in the housing is rotated to show the set dose in the window 18 when
`the scale drum is displaced axially in the housing. The proximal end of the injection member
`is terminated by an end wall 77 which carries an injection button 78 which is by a pivot pin 79
`joumaled in a central bore in said end wall 77.
`
`To set a dose the dose setting button 71 is rotated in a clockwise direction. As the injection
`member is kept non rotatable by its coupling to the driver tube 67 the collaboration between
`the helical recess 75 in the inner wall of the dose setting button 71 and the helical rib 76 on
`the outer wall of the injection element 70 will screw the injection element out through the
`dose setting button so that the injection button 78 is lifted up from the proximal end of the
`housing. Although the driVer tube 67 with its pawl can be rotated in the clockwise direction
`
`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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`Sanofi Exhibit 2