Sanofi-Aventis Deutschland GmbH
`Site Frankfurt Devices
`lndustriepark Hochst
`D-65926 Frankfurt
`
`Sanofi et al. v. Merck
`1 :16-cv-812-RGA
`
`PTX-0553
`
`SoloStar - principles of operation
`
`Project:
`
`SoloStar
`
`Document ID:
`
`AL01-SoloStar-operation
`
`Version:
`
`Date:
`
`0.1
`
`31.08.2006
`
`Keywords:
`
`SoloStar, 51 Ok, principles of operation
`
`CONFIDENTIAL - not to be disclosed to third parties.
`
`Document ID: AL01_R_002
`
`Version: 1 .0
`
`Page 1 of 12
`
`Uncontrolled copies must be checked against controlled copies or original prior to use to ensure version control.
`
`HIGHLY CONFIDENTIAL
`
`SANOFI 00406383
`
`PTX-0553.0001
`
`Sanofi Exhibit 2161.001
`Mylan v. Sanofi
`IPR2018-01676
`
`

`

`CONFIDENTIAL - not to be disclosed to third parties.
`
`Signatures
`
`Andreas Bode
`
`Serpil Heger
`
`·.·.·.··.·.··.·.··.·.·.· ... ·.· .. ·.·.·.·.·.·.·.··.·.··.·.·.·.·.·.·.· .. ·.·.
`
`/Department i>
`.................................
`DOI,
`
`Development
`Projects
`
`·.·.·.··.·.··.·.··.·.·.· ... ·.· .. ·.·.·.·.·.·.·.··.·.··.·.·.·.·.·.·.· .. ·.·.
`
`fbepar1me11i/
`DSM,
`
`Project
`Management
`
`Anke Liewald
`
`Quality
`Assurance
`
`Effective Date:
`
`Equals date of last signature
`
`Document ID: AL01_R_002
`
`Version: 1.0
`
`Page 2 of 12
`
`Uncontrolled copies must be checked against controlled copies or original prior to use to ensure version control.
`
`HIGHLY CONFIDENTIAL
`
`SANOFI 00406384
`
`PTX-0553.0002
`
`Sanofi Exhibit 2161.002
`Mylan v. Sanofi
`IPR2018-01676
`
`

`

`CONFIDENTIAL - not to be disclosed to third parties.
`
`TABLE OF CONTENT
`
`1. DESCRIPTION AND FUNCTION ................................................................................................ 4
`
`OVERVIEW ......................................................................................................................... 4
`1.1
`1.1.1 Description of SoloStar® ............................................................................................... 4
`1.1.2 Cap and Cartridge Holder subassembly ....................................................................... 5
`1.1.3 Mechanism subassembly ............................................................................................. 6
`1.1.4 Differentiating the Insulins ............................................................................................ 7
`1 1.5 Principles of Operation
`8
`1. 1.5. 1
`Selecting a dose...........................
`.. .......................................................................... 8
`1.1.5.2
`Dose limitation (max, end, min).....
`. ........................................................................... 8
`1.1.5.2.1 Minimum dose limit...............
`.. .......................................................................... 9
`1.1.5.2.2 Maximum dose limit...............
`.. .......................................................................... 9
`1.1.5.2.3 End of cartridge limit.............
`. ........................................................................... 9
`1. 1.5.3
`Dispensing, injecting....................
`. ........................................................................... 9
`1. 1.5.4
`Tactile, audible, visual feedback...
`. ......................................................................... 10
`1.1.5.4.1 Dose selection .. .. .. .. .... .. .. .. .. .. .
`.. ........................................................................ 1 O
`1.1.5.4.2 Dose injection ........................................................................................................... 1 O
`. ......................................................................... 10
`1.1.5.4.3 Dose limitation.......................
`.. ............................................. 11
`MATERIALS..
`
`1.2
`
`2.
`
`HISTORY .................................................................................................................................. 12
`
`LIST OF FIGURES
`
`Figure 1 - Apidra® SoloStar® ............................................................................................................. .4
`
`Figure 2 - Lantus® SoloStar® ............................................................................................................ .4
`
`Figure 3 - Cap and Cartridge Holder subassembly ............................................................................. 5
`
`Figure 4 - Mechanism subassembly of Lantus® SoloStar® .................................................................. 6
`
`Figure 5 - Mechanism subassembly of Apidra® SoloStar® ................................................................... 6
`
`Figure 6 - Components of the Mechanism subassembly ..................................................................... 7
`
`Figure 7 - Lantus® SoloStar® ..
`
`...8
`
`Figure 8 - Apidra® SoloStar® .............................................................................................................. 8
`
`Figure 9 - Dose selecting .................................................................................................................. 8
`
`Table 1 - Material List..
`
`.............................................. 11
`
`LIST OF TABLES
`
`Document ID: AL01_R_002
`
`Version: 1.0
`
`Page 3 of 12
`
`Uncontrolled copies must be checked against controlled copies or original prior to use to ensure version control.
`
`HIGHLY CONFIDENTIAL
`
`SANOFI 00406385
`
`PTX-0553.0003
`
`Sanofi Exhibit 2161.003
`Mylan v. Sanofi
`IPR2018-01676
`
`

`

`CONFIDENTIAL - not to be disclosed to third parties.
`
`1.
`
`DESCRIPTION AND FUNCTION
`
`1.1 OVERVIEW
`
`1.1.1 Description of Solo Star®
`SoloStar® injection system is a device that provides a method of accurately injecting a
`selected dose of insulin through a single lumen hypodermic needle. SoloStar® is
`intended to be used for self-injection by patients. Patients who are not able to handle
`the device properly (according to Health Care Professional's assessment) require
`assistance from a third person. SoloStar® system is a disposable insulin injection
`system that by design, cannot be reused.
`In appearance and general handling characteristics, SoloStar® injection system is
`similar to other pen injectors used for the administration of insulin.
`The dose to be injected is pre-selected by rotating a dosage selector at the rear end of
`the device. The number of selected insulin units is displayed in the thread insert (dose
`window) on the side of the pen. Before the injection, a pen injector needle is mounted
`onto the front end of the device and inserted under the skin. The dose is delivered by
`pressing the button until it is in its original end position.
`SoloStar® pen is a fully disposable injection system, offering a simple handling, by
`eliminating the need for cartridge change.
`
`Figure 1 - Apidra® SoloStar®
`
`Figure 2 - Lantus® SoloStar®
`
`The injection system provides a method of accurately injecting a selected dose. Dose
`setting is a mechanical process.
`The dialing mechanism allows dosage in one insulin unit increments. It provides a
`maximum of 80 insulin units in one dosing. The total content of the cartridge is 300
`insulin units.
`For the safety and convenience of the user, as well as for the protection of the
`cartridge, a pen cap has been incorporated as part of the pen system.
`
`Document ID: AL01_R_002
`
`Version: 1.0
`
`Page 4 of 12
`
`Uncontrolled copies must be checked against controlled copies or original prior to use to ensure version control.
`
`HIGHLY CONFIDENTIAL
`
`SANOFI 00406386
`
`PTX-0553.0004
`
`Sanofi Exhibit 2161.004
`Mylan v. Sanofi
`IPR2018-01676
`
`

`

`CONFIDENTIAL - not to be disclosed to third parties.
`
`1.1.2 Cap and Cartridge Holder subassembly
`
`As detailed below, a printed cartridge holder (12) is pre-assembled into the pen cap (13) and
`delivered to the final assembly. The cartridge holder printing helps the patient to determine, as
`an indication, how much insulin is left in the cartridge (14).
`
`A threaded end on the cartridge holder allows the patient to attach a pen-injector needle. A
`needle is not delivered with SoloStar® pen-injector.
`
`C
`
`Pen Cap (13)
`
`Cartridge
`Holder (12)
`
`Cartridg
`e (14)
`
`Figure 3 - Cap and Cartridge Holder subassembly
`
`There are snap features between cartridge holder and pen cap that allow the pen cap to be
`fixed onto the cartridge holder in defined positions. The remoyal method for the cap is pull(cid:173)
`off The pen cap is designed to protect the cartridge from damage and dirt. The clip on the pen
`cap allows attachment to a shirt or jacket pocket
`
`Document ID: AL01_R_002
`
`Version: 1.0
`
`Page 5 of 12
`
`Uncontrolled copies must be checked against controlled copies or original prior to use to ensure version control.
`
`HIGHLY CONFIDENTIAL
`
`SANOFI 00406387
`
`PTX-0553.0005
`
`Sanofi Exhibit 2161.005
`Mylan v. Sanofi
`IPR2018-01676
`
`

`

`CONFIDENTIAL - not to be disclosed to third parties.
`
`1.1.3 Mechanism subassembly
`
`SoloStar® mechanism subassembly consists of eleven components which are automatically
`assembled. All components carry many different functions and interact with each other.
`Examples for Lantus® and Apidra® are provided.
`
`:;::;::~~;;;;~~~,:-
`
`Figure 4 - Mechanism subassembly of Lantus® SoloStar®
`
`Figure 5 - Mechanism subassembly of Apidra® SoloStar®
`
`The drive sleeve (1) forms the backbone of the mechanism and carries clutch (2) and number
`sleeve (3) A metal spring (4) which is located between clutch and drive sleeve serves for
`audible and tactile feedback during dialing.
`
`When selecting the dose, the dosage selector (5) is turned clockwise to increase and counter
`clockwise to decrease the selected dose. Correction of the selected dose can be done without
`expelling insulin. Dosage selector and number sleeve are firmly clipped together and form an
`integral unit. The number sleeve has even numbers and indication lines for uneven numbers
`printed onto its surface which are visible to the patient through a thread insert (dose window)
`(6). The thread insert is rotated over the number sleeve and snapped into the body (7).
`
`Document ID: AL01_R_002
`
`Version: 1.0
`
`Page 6 of 12
`
`Uncontrolled copies must be checked against controlled copies or original prior to use to ensure version control.
`
`HIGHLY CONFIDENTIAL
`
`SANOFI 00406388
`
`PTX-0553.0006
`
`Sanofi Exhibit 2161.006
`Mylan v. Sanofi
`IPR2018-01676
`
`

`

`CONFIDENTIAL - not to be disclosed to third parties.
`
`Number
`
`Number
`
`Last Dose
`
`Bo
`
`Bearing ( I 0)
`
`Lead
`
`Screw
`
`'Ose
`
`Lea
`d
`Sere
`
`Drive
`
`Figure 6 - Components of the Mechanism subassembly
`
`Once the dose is selected the patient has to push onto the injection button (8) to inject the
`insulin. The injection button is located next to the dosage selector and operates the clutch
`mechanism. Pressing the button disengages clutch and number sleeve and thereby allows the
`number sleeve to rotate back into the body. While the clutch is disengaging from the number
`sleeve it compresses the metal spring and thereby locks with the drive sleeve to prevent the
`latter from rotating relative to the number sleeye and body. By pressing the injection button
`and rotating the number sleeve back the drive sleeve moves in axially without rotation. The
`lead screw (9) is located inside the drive sleeve and body and is connected to both via threaded
`interfaces. While the dose is selected and the drive sleeve is rotated the lead screw does not
`move. When the drive sleeve is pushed in, the lead screw rotates and by this action, advances
`axially towards the cartridge bung. The connection between lead screw and cartridge bung is
`the bearing (1 O) which applies the force from the mechanism onto the bung evenly.
`With every unit expelled the last dose nut (11) advances axially on the drive sleeve, to
`eventually hit a stop which corresponds to 307 units. This limits the amount of insulin to what
`can be accurately delivered from the cylindrical part of the cartridge. Since the labeled volume
`is 300 units the limitation to 307 units allows for removing air which maybe trapped inside the
`cartridge.
`
`1.1.4 Differentiating the Insulins
`
`Providing different drugs in the same device bears the risk of mixing up the drugs. The pen(cid:173)
`type injectors available on the market typically offer basal and short acting insulin from the
`same device, identifying the contents by means of an adhesive sticker.
`
`In addition to the sticker Solo Star® is produced in different colors for the insulins being offered
`with the device. Having different color devices for different drugs minimizes the potential of
`drug mix-up.
`
`Examples for Lantus® and Apidra® are provided.
`
`Document ID: AL01_R_002
`
`Version: 1.0
`
`Page 7 of 12
`
`Uncontrolled copies must be checked against controlled copies or original prior to use to ensure version control.
`
`HIGHLY CONFIDENTIAL
`
`SANOFI 00406389
`
`PTX-0553.0007
`
`Sanofi Exhibit 2161.007
`Mylan v. Sanofi
`IPR2018-01676
`
`

`

`CONFIDENTIAL - not to be disclosed to third parties.
`
`Figure 7 - Lantus® SoloStar®
`
`Figure 8 - Apidra® SoloStar®
`
`1.1.5 Principles of Operation
`
`1.1.5.1 Selecting a dose
`
`For dose selection the dosage selector has to be turned clockwise to increase and counter
`clockwise to decrease the dose.
`
`Figure 9 - Dose selecting
`
`The number sleeve is locked to the dosage selector and therefore turns as well, displaying
`increasing or decreasing numbers inside the thread insert (dose window). During the dose
`selection the clutch is engaged with the number sleeve and transfers the rotation to the drive
`sleeve. The metal spring which is located between the distal end of the clutch and the middle
`flange of the drive sleeve is locked inside the body with respect to rotation by means of
`splines. Teeth at the distal end of the clutch ride over the metal spring causing both an audible
`and tactile feedback.
`
`The lasl dose nut is localed between the middle flange and the end flange of lhe drive sleeve
`and is connected via threads. While the drive sleeve rotates the last dose nut moves axially as
`it is locked to the body with respect of rotation. The axial movement of the last dose nut
`corresponds to the selected dose.
`
`The lead screw is not moving during the dose selection process.
`
`1.1.5.2 Dose limitation (max, end, min)
`
`Dose selection is limited to a max. dose of 80 units per injection. It is also not possible to select
`a dose below O units or above what is left in the cartridge.
`
`Document ID: AL01_R_002
`
`Version: 1.0
`
`Page 8 of 12
`
`Uncontrolled copies must be checked against controlled copies or original prior to use to ensure version control.
`
`HIGHLY CONFIDENTIAL
`
`SANOFI 00406390
`
`PTX-0553.0008
`
`Sanofi Exhibit 2161.008
`Mylan v. Sanofi
`IPR2018-01676
`
`

`

`CONFIDENTIAL - not to be disclosed to third parties.
`
`1.1.5.2.1 Minimum dose limit
`
`When selecting and correcting a dose the patient may decide to quit the injection process and
`dial back down to 0. Stop features between dosage selector and thread insert support the O unit
`position of the pen. When dialing counter-clockwise the dosage selector will eventually
`engage with the thread insert to prevent rotating beyond the O unit position. The thread insert
`is fixed firmly to SoloStar® pen body and because of its height, the O unit stop gives a distinct
`stop feedback, preventing accidental dialing past the O point.
`
`1.1.5.2.2 Maximum dose limit
`
`Dialing beyond the maximum dose is limited as well. The maximum selectable dose with
`SoloStar® pen is 80 units. If the patient tries to select a higher dose, number sleeve and thread
`insert engage rotationally preventing the number sleeve from moving further. Dosage selector
`and number sleeve are firmly affixed to each other during the assembly process; several form
`fit interfaces transfer torque without relative movement of dosage selector and number sleeve.
`
`1.1.5.2.3 End of cartridge limit
`
`As per ISOl 1608-1 :2000 requirement a pen-type injector must not allow the patient to select a
`dose which is greater than what is left inside the cartridge. In order to fulfill this requirement
`the last dose nut component was designed to irreversibly travel inside the mechanism to
`eventually hit a stop and block the mechanism for dialing greater doses.
`
`The last dose nut is located between the middle flange and the end flange of the drive sleeve
`and is connected via threads. As the drive sleeve rotates, the last dose nut moves axially along
`the length of the drive sleeve, since it is confined in the body so as to prevent its rotation. The
`axial movement of the last dose nut corresponds to the selected dose.
`
`To allow for initial priming to remove air that may be trapped inside the cartridge, the
`mechanism is able to deliver up to 307 units. When the patient tries to dial more than
`307 units, e.g. if only 20 units are left in the cartridge but the patient tries to dial to 21, the last
`dose nut will hit a stop feature on the middle flange of the drive sleeve corresponding to
`307 units total. Torque is transmitted from last dose nut to the body and also to the drive
`sleeve. From there the end stop feedback is transferred to the clutch, the number sleeve, and
`finally to the patients finger via the dosage selector.
`
`1.1.5.3 Dispensing, injecting
`To dispense the selected dose the injection button has to be pushed all the way in. The
`injection button is located behind the dosage selector and it operates the clutch mechanism.
`Pressing the button disengages clutch and number sleeve and therefore allows the number
`sleeve to rotate back into the body. As the clutch is disengaging from the number sleeve, it
`compresses the metal spring and by this action locks with the drive sleeve to prevent it from
`rotating relative to the number sleeve and body. As a result, by pressing the injection button,
`the drive sleeve moves in axially without rotation and the number sleeve rotates back into
`position for the next dose selection. The lead screw is located inside the drive sleeve and body
`and is connected to both via threaded interfaces. When the dose is being selected and the drive
`sleeve is rotating, the lead screw does not move. When the drive sleeve is then pushed in
`
`Document ID: AL01_R_002
`
`Version: 1.0
`
`Page 9 of 12
`
`Uncontrolled copies must be checked against controlled copies or original prior to use to ensure version control.
`
`HIGHLY CONFIDENTIAL
`
`SANOFI 00406391
`
`PTX-0553.0009
`
`Sanofi Exhibit 2161.009
`Mylan v. Sanofi
`IPR2018-01676
`
`

`

`CONFIDENTIAL - not to be disclosed to third parties.
`
`axially by the dispensing button without rotation, the lead screw is forced to rotate and as a
`result advances axially to exert force on the cartridge bung.
`
`From a design perspective, dose accuracy is determined by the lead screw. The thread to the
`drive sleeve translates the movement of the operator's thumb into the movement of the
`cartridge bung This is done by the pitch ratio of thread to drive sleeve and thread to body.
`
`When pressing the injection button, the drive sleeve moves axially along the interior of the pen
`body, without any rotation. The lead screw is forced to turn, since it is positioned inside the
`body thread thal transfers the drive sleeve pushing force to ii. As it turns inside the drive
`sleeve thread, the lead screw is also turning inside the body thread, advancing toward and
`applying pressure to the cartridge bung.
`
`1.1.5.4 Tactile, audible, visual feedback
`
`SoloStar® provides either visual, tactile, or audible feedback, or a combination of the three to
`many operations which are described in the following sections.
`
`1.1.5.4.1 Dose selection
`
`When dialing a loud clicking sound can be heard and an associated tactile click can be felt.
`This is caused by the metal spring which is located between drive sleeve, clutch, and body.
`Additionally, numbers, corresponding to the selected dose are displayed within the thread
`insert. Uneven numbers are not shown but lines between even numbers indicate selection of
`uneven units.
`
`1.1.5.4.2 Dose injection
`
`Ratchet arms on the clutch generate a gentle click during the injection. In parallel, the number
`sleeve rotates back.
`
`1.1.5.4.3 Dose I imitation
`
`Tactile feedback is provided when dose limits are experienced.
`
`Additionally, for the minimum dose stop at O units next to the "O" a "l" is visible on the
`number sleeve indicating the direction of rotation to increase the selected dose. Please note
`that the "l" is the only odd number which is printed onto the number sleeve. On the other side
`of the "O" where the "-1" would have to be located there is blank space supporting the obvious
`fact that no negative dose can be injected.
`
`For the maximum dose stop at "80" units the printing supports the perception of a limit as
`well. While the "80" is located in alignment with the notch inside the thread insert, a "78" is
`just visible at the top end of the window. The patient could dial back with a counter-clockwise
`movement. On the other side of the "80", i.e. at the bottom end of the window, no number is
`visible. From dialing up and down the patient has learned that the next higher selectable dose
`is visible below the current dose number. Therefore, since no number is visible, no higher dose
`is selectable.
`
`Document ID: AL01_R_002
`
`Version: 1.0
`
`Page 10 of 12
`
`Uncontrolled copies must be checked against controlled copies or original prior to use to ensure version control.
`
`HIGHLY CONFIDENTIAL
`
`SANOFI 00406392
`
`PTX-0553.0010
`
`Sanofi Exhibit 2161.010
`Mylan v. Sanofi
`IPR2018-01676
`
`

`

`CONFIDENTIAL - not to be disclosed to third parties.
`
`1.2 MATERIALS
`For the external parts of SoloStar® the following materials are used: Polycarbonate,
`Polypropylene and Polybutelene terephthalate. In addition color additives are worked
`up in Polycarbonate, Polypropylene and Polybutelene terephthalate. These materials
`have been tested for biocompatibility according ISO 10993 part 1.
`The following materials are used in the construction of SoloStar®. Please note that
`none of the following materials make contact with the drug product. Sanofi-Aventis
`has provided FDA information on the in-use stability and stability of the drug product in
`3 ml cartridge in the drug product section, Section 3.2.P of the NOA 21 - 081 and 21
`- 629 for Lantus® and Apidra® respectively. Information on the suitability of the
`container closure system for the drug products has been provided in section 3.2.P.7
`Container Closure System of these submissions. Please refer to
`the original
`submissions, amendments, supplements and annual reports for information related to
`the 3.0 ml cartridges in conjunction with their use with these two products.
`
`Table 1 - Material List
`
`Component
`
`Pen cap
`
`Cartridge holder
`
`Thread insert
`
`Dosage selector
`
`Material
`
`Polypropylene (PP)
`
`Polypropylene (PP)
`
`Polycarbonate (PC)
`
`Polycarbonate (PC)
`
`Lead screw bearing
`
`Polyoxymetylene (POM)
`
`Lead screw
`
`Drive sleeve
`
`Metal spring
`
`Clutch
`
`Number sleeve
`
`Last dose nut
`
`Outer body
`
`Polybutylene terephthalate (PBT)
`
`Polyoxymetylene (POM)
`
`Stainless steel
`
`Polyoxymetylene (POM)
`
`Polybutylene terephthalate (PBT)
`
`Polyoxymetylene (POM)
`
`Polypropylene (PP)
`
`Polybutylene terephthalate (PBT)
`Injection button
`The documents included in section 1 are given in the following table:
`
`Document ID: AL01_R_002
`
`Version: 1.0
`
`Page 11 of 12
`
`Uncontrolled copies must be checked against controlled copies or original prior to use to ensure version control.
`
`HIGHLY CONFIDENTIAL
`
`SANOFI 00406393
`
`PTX-0553.0011
`
`Sanofi Exhibit 2161.011
`Mylan v. Sanofi
`IPR2018-01676
`
`

`

`CONFIDENTIAL - not to be disclosed to third parties.
`
`2.
`
`HISTORY
`
`0.1
`
`01.09.2006
`
`Andreas Bode
`
`First version
`
`Document ID: AL01_R_002
`
`Version: 1.0
`
`Page 12 of 12
`
`Uncontrolled copies must be checked against controlled copies or original prior to use to ensure version control.
`
`HIGHLY CONFIDENTIAL
`
`SANOFI 00406394
`
`PTX-0553.0012
`
`Sanofi Exhibit 2161.012
`Mylan v. Sanofi
`IPR2018-01676
`
`