Claims for Patent: 5,334,162

Summary for Patent: 5,334,162

Title:	Cartridge assembly for a lyophilized compound forming a disposable portion of an injector pen and method for same
Abstract:	A cartridge assembly for holding a lyophilized product, forming a disposable portion of a pen injector includes a cylindrical glass cartridge adapted to receive the product, a closure cap, a cartridge case, and a plunger mechanism. The closure cap is adapted to retain an elastomeric disc seal during lyophilization and includes diametrically opposed ledges. The closure cap and seal are adapted to cover a neck portion of the ampule, the neck portion having on its end a radially extending circumferential flange. The ledges of the closure cap and the flange of the neck portion allow the closure cap to remain open during lyophilization, oxygen purge and nitrogen overlay. An oval-shaped indentation formed on the inside of the closure cap aids in snapping the closure cap about the flange without crimping to retain the closure cap underneath the flange. Reconstitution of the lyophilized drug is accomplished without foaming by use of an obliquely angled connector which causes the diluent to indirectly impinge on the drug. The injection pen and cartridge assembly cooperate such that the length of travel of the plunger rod during retraction is less than the axial length of a recess in the rod tip.
Inventor(s):	Harris; Dale C. (Fairland, IN)
Assignee:	Eli Lilly and Company (Indianapolis, IN)
Application Number:	08/031,683
Patent Claims:	1. A method of lyophilizing and sealing an injectionable product within a cartridge, the method comprising the steps of: providing an elongate cartridge having on a first end thereof a shoulder, a rim defining a first opening and having a circumferential radially outwardly extending flange adjacent said first opening, and a neck disposed axially between said flange and shoulder, said neck having a diameter smaller than said flange and shoulder, said cartridge including a second opening on a second end thereof distal said first opening; inserting a plunger in said second opening; providing a cap having a cylindrical portion and a seal, said cylindrical portion including an open bottom receivable over said neck, said cap including a top having an opening therein for receipt of a needle therethrough, at least one vent circumferentially disposed in said cap, and at least two deformable ledges on said cap extending radially inwardly from said cylindrical portion axially below said vent, said seal being axially disposed between said vent and said top so as to block said top opening; inserting the product to be lyophilized into said cartridge; placing said cap onto said cartridge such that said deformable ledges rest upon said flange and said vent is in fluid communication with said cartridge first opening; placing said cartridge with said cap in a lyophilizing chamber; lyophilizing the product; and closing said cap by exerting a downward pressure upon said cap such that said deformable ledges yieldably snap around said flange and into said neck to be lockingly retained therein, said vent is blocked from communication with said cartridge first opening, and said seal is pressed into sealing engagement with said rim by downward pressure exerted by said top thereby providing an air impermeable barrier between said top opening and said cartridge first opening. 2. The method of claim 1, wherein the step of closing said cap is preceded by the steps of: purging oxygen from said cartridge; and providing a nitrogen overlay in said cartridge. 3. The method of claim 1, further comprising the steps of: providing a sleeve having a first open end for receiving said cartridge and a radially inwardly extending stop; and placing said cartridge into said first open end of said sleeve such that said cartridge is positively axially retained in said sleeve against said stop. 4. The method of claim 3, further including the subsequent step of permanently attaching said sleeve to said cap. 5. The method of claim 3, wherein said sleeve includes a second open end distal said first open end and axially below said sleeve stop, and the step of placing said cartridge into said sleeve is preceded by the step of inserting a plunger rod tip having a head in said sleeve such that said plunger rod tip extends from said second opening and said head is axially adjacent said plunger. 6. The method of claim 5, further including the step of capturing said head between said sleeve ledge and said plunger. 7. The method of claim 1, wherein the step of placing the cartridge in a lyophilizing chamber includes supporting said cartridge on a first surface, and the step of closing said cap includes exerting a downward pressure upon said cap by contact of a second surface upon said cap induced by relative vertical movement between said first and second surfaces. 8. A cartridge assembly for holding a lyophilized drug and forming a disposable part of an injection pen, the cartridge assembly comprising: an elongate cartridge having on a first end thereof a shoulder, and a rim defining a first opening and having circumferential radially outwardly extending flange adjacent said first opening and a neck disposed axially between said flange and shoulder, said neck having a diameter smaller than said flange and shoulder, said cartridge including a second opening on a second end thereof distal said first opening; a cap disposed on said first end of said cartridge, said cap having a first cylindrical portion including an open bottom received over said first end, a top having an opening therein for receipt of a needle therethrough, and at least two elastically deformable ledges extending radially inwardly from said first cylindrical portion and lockingly retained under said neck flange; a resilient seal in said cap disposed between said first opening and said top opening and forming an impermeable barrier therebetween; a sleeve radially disposed about and permanently attached to said cap; and a plunger rod tip slidably disposed in said sleeve, said plunger rod tip including a head axially adjacent said plunger for exerting pressure against said plunger during administration of the drug. 9. The cartridge assembly of claim 8, wherein said head exerts a uniform pressure against said plunger during administration of the drug. 10. The cartridge assembly of claim 8, wherein said sleeve is permanently attached to said cap. 11. The cartridge assembly of claim 8, wherein said sleeve includes a first cylindrical portion adapted to receive said cartridge and a second cylindrical portion axially below said first cylindrical portion and concentric therewith, and a radially inward circumferentially extending ledge defined at the junction of said first and second cylinder for axially retaining said one end of said cartridge. 12. The cartridge assembly of claim 11, further including means for connecting said sleeve to an injection pen. 13. The cartridge assembly of claim 12, wherein said means for connecting said sleeve to the injection pen comprises threads on said second cylindrical portion. 14. The cartridge assembly of claim 8, wherein said cap further includes means for connecting said cap to a needle assembly. 15. The cartridge assembly of claim 8, wherein said rim of said cartridge outwardly tapers for compressingly sealing said resilient seal between said cartridge and said cap. 16. The cartridge assembly of claim 8, wherein said cap includes an oval shaped wall carrying said ledges wherein said wall is thinner along the major axis of the oval than along the minor axis of the oval, and said ledges are disposed generally on the minor axis of the oval. 17. A cap and cartridge assembly for lyophilizing a drug within the cartridge and sealing the cartridge after lyophilization, the cartridge having a first end defining a first opening therein, the first end including a circumferential radially outwardly extending flange adjacent the first opening, said cap including a reduced diameter neck adjacent said flange, the cap comprising: a first cylindrical portion having an open bottom end receivable over said cartridge first end; a top having an opening therein for receipt of a needle therethrough; at least one vent opening circumferentially disposed in said first cylindrical portion; said first cylindrical portion having an oval-shaped inner wall and a deformable ledge in said cap on said oval-shaped wall and extending radially inwardly at a position axially below said vent, said ledge being disposed generally on the minor axis of the oval; said cap adapted for a first position during lyophilization whereby said deformable ledge rests upon the flange of the cartridge such that said vent is in communication with the cartridge opening, said cap adapted for a second position after lyophilization whereby said deformable ledge yieldably snaps around the flange such that said deformable ledge is lockingly retained thereunder in the neck, said vent is closed from communication with the cartridge opening, and the seal is compressed into sealing engagement with the cartridge opening by downward pressure exerted by said top thereby providing an air impermeable barrier between said top opening and the cartridge opening. 18. The cap and cartridge assembly of claim 17, wherein said oval-shaped inner wall extends the inner axial length of said first cylindrical portion. 19. The cap and cartridge assembly of claim 17, wherein said deformable ledge comprises two circumferential and inwardly extending ledges separated by two arcuate portions of said oval-shaped wall and said ledges are located on the minor axis of said oval-shaped wall. 20. The cap and cartridge assembly of claim 17, wherein said top includes external threads for engaging a transfer needle assembly. 21. The cap and cartridge assembly of claim 17, further including a second cylindrical portion axially below said first cylindrical portion and concentric therewith, said second cylindrical portion having an axial length so as to partially extend radially about the cartridge neck when said cap is in the open position. 22. The cap and cartridge assembly of claim 17, wherein said oval-shaped wall is thinner along the major axis of the oval than along the minor axis of the oval. 23. The cartridge assembly of claim 11 wherein said plunger rod tip is captured by said ledge of said sleeve to thereby retain said plunger rod tip in said sleeve.

Details for Patent 5,334,162

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Eli Lilly And Company	HUMATROPE	somatropin	For Injection	019640	06/23/1987		2041-03-07
Eli Lilly And Company	HUMATROPE	somatropin	For Injection	019640	10/16/1986		2041-03-07
Eli Lilly And Company	HUMATROPE	somatropin	For Injection	019640	02/04/1999		2041-03-07

International Patent Family for US Patent 5,334,162

Country	Patent Number	Estimated Expiration
South Africa	941801
World Intellectual Property Organization (WIPO)	9421213
United States of America	5454786
Ukraine	27970
Russian Federation	2126242
Poland	310632