FORM 2
THE PATENT ACT 1970
(39 of 1970)
&
The Patents Rules, 2003
COMPLETE SPECIFICATION
(See section 10 and rule 13)
1. TITLE OF THE INVENTION: DEVICE FOR ATTACHMENT TO A NEEDLE ASSEMBLY TO VARY THE LENGTH OF THE NEEDLE
2. APPLICANT (S)

(a) NAME: WOCKHARDT LTD.
(b) NATIONALITY: INDIAN
(c) ADDRESS: D-4, M.I.D.C. Area, Chikalthana, Aurangabad - 431210
(M.S.) India
3. PREAMBLE TO THE DESCRIPTION
The present invention provides a device for the delivery of biological material across the biological tissue. The device comprises of an extender which when attached to a needle hub of a needle assembly allows protrusion of desired length of needle from the distal end of the extender.
The following specification particularly describes the invention and the manner in which it is to be performed.


4. Description
The present invention provides a device for the delivery of biological material' across the biological tissue. The device comprises of an extender which when attached to a needle hub of a needle assembly allows protrusion of desired length of needle from the distal end of the extender.
Dosed biological material delivery devices, often referred to as "injection pen device" are commonly used for routine injection of biological materials.
Dosed biological material delivery devices are a preferred means of delivery wherever the volume of biological material delivered needs to be variable but accurate, critical, small and needs to be administered very frequently. Hence, "injection pen device" refer generally to any and all free- standing portable device containing a plurality of doses of a biological material liquid which can be operated by a patient for self injection to deliver metered doses of the liquid to the patient's body on a plurality of occasions.
US patent No 6,200,296 discloses a needle assembly for a medication delivery pen or hypodermic syringe having a usable length of 5 mm (0.197") that delivers a dose of medication to a proper location in the tissue "strata" or subcontinuous layer without the need for the user or patient to "pinch-up" the skin layer during the injection.
US patent No 7,186,235 discloses an apparatus and method for intradermally administering a pharmaceutical composition or other substance into and through the skin of a mammalian body in a manner that avoids or eliminates excess pain and discomfort normally caused as a result of the microabraders or microneedles entering the epithelial layers beneath the stratum corneum.
US patent No 6,482,176 discloses to a method for controlling the introduction depth of an injection needle which is mounted inside a needle introduction device so as to be capable
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of axial displacement relative to an injection device coupled to said needle introduction device or arranged in the same.
US patent no 5,944,700 discloses an extender that is rotatably attached to a hub on the pen needle to set the pen needle to a desired injection length. This injection length serves the purpose of intravaneous, subcutaneous and intra muscular delivery.
US patent No 6,554,238 discloses that needle has an injection part extending axially from the hub and terminating in a skin piercing obliquely cut end.. The length of the injection part is between 4 and 6 mm, thereby facilitating a proper subcutaneous injection.
US patent application No 20070118073A1 relates to an apparatus and method for intradermally administering a pharmaceutical composition or other substance into and through the skin of a mammalian body in a manner that avoids or eliminates excess pain and discomfort normally caused as a result of the microabraders or microneedles entering the epithelial layers beneath the stratum corneum. In a preferred embodiment, the apparatus is a microdevice with an array of microabraders or microneedles with a manipulating member.
EP No 1625870 relates to needle for intradermal delivery of substance into human or animal skin comprises hub to limit penetration of the needle into the skin, and outlet so positioned to prevent leakage of the substance to the skin surface.
The present inventors while working for suitable extender design which when attached to a needle hub of a needle assembly the protruded portion of the needle from the distal end of the extender extends to a desired length. The desired length is between 3 um to about 4.5mm which specifically allows dermal/epidermal or transdermal delivery of biological material.
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Delivery of pharmaceutically active ingredient to dermal layer of the skin has the advantages of (i) fast on set off action and (ii) cost efficient as there is no need to fabricate separate small length needles. The fabrication of small length needles is expensive and requires precision manufacturing process.
One of the aspects of the invention discloses a device which comprises of an extender comprising a proximal portion and a distal portion; The proximal portion of the extender is shaped and has a length sufficient enough to fit on to the needle hub of the needle assembly having a needle length of about 1 mm and more of an injection pen device; The shaped distal portion of the extender has a length such that the protruded portion of the needle from distal end of the extender has a desired length of between 3um to 4.5 mm which specifically allows dermal/epidermal or transdermal delivery of biological material.
The conventional hypodermic needle attached to a needle hub will have varying lengths. The projected needle length of the hypodermic needle from the distal portion of the needle hub can be less than 6mm or more than 9mm, more preferably between 6mm to 9mm long. The needle gauge can be anywhere between 22gauge to 34 gauge and more preferably 30 or 31 gauge. The 30 gauge or 31 gauge conventional needles have outer diameters of 305 urn and 254 urn and inner diameter of around 200 urn.
The term "microneedle" refers to a device for transdermal or intradermal delivery or removal of fluids without many of the risks associated with standard syringes. Microneedle is designed to pierce the stratum corneum skin barrier layer in a minimally invasive and pain-free manner to provide transient pathways for the delivery of macromolecules to the underlying skin epidermis. Since the needle is short, it does not reach the nerve-rich regions of the lower parts of the skin. As a consequence, the stimulus caused by microneedle insertion into the skin is weak and cause less pain.
The various studies on pain perception reveal the following facts.
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Upto 150 um length (pain is almost insignificant)
From 150 um to 200 um ( weak to very mild perception)
From 500 um- 750 um and a width of 50 um ( 5 - 10% of the sensation produced by a
26 gage hypodermic needle) i.e. upper end for pain perception commencement can be
considered as 500 um.
"Biological Material Storage" may mean a syringe or cartridge containing suitable pharmaceutical substance.
The term proximal portion means the portion which is towards the dose setting end and the distal portion means the portion which is towards the needle end. The term proximal end means towards the dose setting end and distal end means towards the needle end.
As used herein, the term " biological material " refers to an agent which possesses therapeutic, prophylactic, or diagnostic properties in vivo, for example when administered to an animal, including mammals, such as humans. The biological material is selected from the group comprising of peptides, proteins, carbohydrates, nucleic acid molecules, lipids and other pharmaceutically active ingredients or combinations thereof.
The pharmaceutically active ingredients may be one or more of anesthetics, analgesics, anti bacterials, anti virals, antiadrenergics, antiamebics, antianginals, antiarrhythmics, antibiotics, anticoagulants, anticonvulsants, antidepressants, antidiabetics, antidiuretics, antidyskinetics, antiemetics, antifungals, antihistaminics, antihyperparathyroids, antihypertensives, antiinflammatories, antimigraines, antineoplastics, antineoplastics, antiprotozoals, antipsychotics, antispasmodics, antithrombotics, antiulceratives, anxiolytics, astringents, bone resorption inhibitors, bronchodilators, cardiotonics, cholinergics, diaprostic agents, diuretics, hormones, steriods, hydrochloride as anineoplastic, hypnotics, immunomodulators, immunosuppresants, mucolytics, muscle relaxants, neuromuscular blocking agents, oxytocics, vasodilator and the like.
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The pharmaceutically active ingredients may further include one or more ketamine, chloroprocaine hydrochloride, alfentanil, amikacin, abacavir, bretylium tosylate, metronidazole, diltiazem hydrochloride, ciprofloxacin, dextran sulfate sodium, fosphenytoin sodium, rubidium chloride, insulin, desmopressin acetate, haloperidol lactate, dimenhydrinate, abelcet, diphenhydramine hydrochloride, paricalcitol, diltiazem hydrochloride, ketorolac, dihydroergotamine mesylate, mitoxantrone hydrochloride, leuprolide acetate, metronidazole, aripiprazole, dicyclomine hydrochloride, dipyridamole, cimetidine hydrochloride, diazepam, zinc chloride, zoledronic acid, aminophyllin, digoxin, pyridostigmine bromide, diatrizoate sodium, furosemide, estrogen, androgen and the like, steriods such as glucocorticoid and the like, mechlorethamine hydrochloride, etomidate, mitoxantrone hydrochloride, tacrolimus, acetylcysteine, baclofen, vecuronium bromide, oxytocin nitroglyceine and the like.
In many cases protruded needle length from the distal end of the distal portion of the extender may be less than 1 mm, in which case it would function as a microneedle. The length of the microneedle typically is between about 10 um and 1 mm, preferably between 100 um and 500 um? and more preferably between 150 um and 350 um. The length is selected for the particular application, accounting for both an inserted and un inserted portion. In transdermal applications, the "insertion depth" of the microneedle is preferably less than about 500 um, so that insertion of the microneedles into the skin does not penetrate into the dermis, thereby avoiding contacting nerves which may cause pain. In such applications, the actual length of the microneedle typically is longer, since the portion of the microneedle distal the tip may not be inserted into the skin; the uninserted length depends on the particular device design and configuration. The actual (overall) height or length of microneedle should be equal to the insertion depth plus the un inserted length.
In one of the aspects of the invention the proximal portion is cylindrical in shape and distal portion is conical in shape.
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In one of the aspects of the invention the cylindrical portion has either protrusions or threads on its internal surface.
In one of the aspects of the invention the protrusions on its internal surface results in good frictional contact with outside surface of the needle hub.
In one of the aspects of the invention the suitable material for manufacturing device include one or metals or non biodegradable polymers.
Suitable materials for manufacturing needle (8) or extender (9) include one or more metals. The metals can be selected from the group comprising of pharmaceutical grade stainless steel, gold, titanium, nickel, iron, tin, chromium, copper, palladium, platinum, alloys, silicon, silicon dioxide, and combinations thereof.
Suitable materials for manufacturing extender (9) also include one or more non¬biodegradable polymers which include one or more cellulose, polycarbonate, polyester or polyacryl amides.
In one of the aspects of the invention , the biological material is selected from the group comprising of peptides, proteins, carbohydrates, nucleic acid molecules, lipids and other pharmaceutically active ingredients and combinations thereof.
An injection pen device that would be used for the administration of set dose of the biological material is detailed below. The injection pen device used for precise administration of dose is. described in detail with references to the drawing.
Figure 1 Mechanism for discharge of biological material through needle attached to an injection pen device - A - Existing Cartridge / Syringe and pen ; B - Existing needle hub and cap
Figure 2 Mechanism for discharge of biological material through a needle dimensioned shorter than original length on attachment of an extender - A- Existing Cartridge /
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Syringe and pen ; B- Existing needle hub and cap ; C - Extender attachment to needle
hub with needle cap removed
Figure 3 Components of injection pen device ( Three dimensioned one)
Figure 4 Injection pen device with a needle cap (Three dimensioned one)
Figure 5 Injection pen device with a needle cap removed and extender in position (Three
dimensioned one)
Figure 1 shows the injection pen device (1) where in present needle and a cap (5) that would be associated with a pen. Needle hub (7) has an internal thread (6) that mates with the cartridge or syringe (2) and needle (8) extends on both sides of the needle hub (7). The needle (8) which extends from the distal end of the needle hub may be less than 6mm long or more than 6mm long, more preferably 6 mm to 9mm long. On attachment of needle hub (7) to the cartridge or syringe (2) by screw mechanism or any other means, needle (8) which extends on to the internal of the cap pierces the rubber seal (3) of the cartridge or syringe (2) and establishes contact with the biological material in the cartridge or syringe (2). Needle cap (5) is removed and set dosage of the biological material is administered to a patient.
Figure 2 shows the proposed system wherein a device comprises an extender (9) which has two portions namely the proximal portion and the distal portion . The extender (9) on attachment to the needle hub (7) of the needle assembly results in a protruded portion of the needle from the distal end of the extender (9) of desired length. It could be possible that that the length of the protruded portion of the needle from the distal end of the extender (9) may be less than 1mm or more than 1 mm. More preferably the length of the protruded portion of the needle from the distal end of the extender (9) would be in the range 3 urn to 4.5 mm. It could also be that when the length of the protruded portion of the needle from the distal end of the extender (9) is less than 1mm, needle may perform the task of a microneedle.
The proximal portion (12) of the extender (9) has the shape and dimension as to correspond and fit on to the needle hub (7) of the needle assembly. The length of the
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shaped distal portion (11) is such that the protruded portion of the needle from the distal end of the extender (9) is of desired length. The desired length is between 3 fim to 4.5mm which specifically allows dermal/epidermal or transdermal delivery of biological material.
Figure 2(C) shows the extender (9) with needle cap removed and fitted on to needle hub of the needle assembly. In one of the embodiments shown, the proximal portion (12) is cylindrical in shape and whose length corresponds to the length of the needle hub. Inside diameter of the proximal portion of the extender would be such that it would tight fit on to the outside diameter of the needle hub. There may be serrations on the outside surface of the needle hub (7) and protrusions or grooves on inside surface of the proximal portion of the extender (9) to achieve the tight fit of the needle hub (7) and extender (9).
Alternatively, there may be threads on the outside surface of the needle hub which would mate with the inside thread of the proximal portion of the extender (9).
Distal end (11) of the embodiment shown in figure 2 (c) is so dimensioned as to achieve the protruded portion of the needle of desired length.
The proximal and distal portions of the extender (9) are either separately made and attached or molded as an integral device. The extender (9) shown in Figure 2 is an integral one.
While the present invention has been described in terms of its specific embodiments, certain modifications and equivalents will be apparent to those skilled in the art and are intended to be included within the scope of the present invention.
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WE CLAIM:
1 A device comprises of an extender comprising a proximal portion and a distal
portion; The proximal portion of the extender is shaped and has a length sufficient enough to fit on to the needle hub of the needle assembly having a needle length of about 1 mm and more of an injection pen device; The shaped distal portion of the extender has a length such that the protruded portion of the needle from distal end of the extender has a desired length of between 3um to 4.5 mm which specifically allows dermal/epidermal or transdermal delivery of biological material.
2 The device as claimed in claim 1, wherein the proximal portion is cylindrical in
shape and distal portion is conical in shape.
3 The device as claimed in claim 2, cylindrical portion has either protrusions or
, threads on its internal surface.
4 The device as claimed in claim 3, protrusions on its internal surface results in good frictional contact with outside surface of the needle hub.
5 The device as claimed in claim 1, wherein the suitable material for manufacturing device include one or metals or plastics.
6 The device as claimed in claim 1, wherein the suitable material for manufacturing needle include one or more metals.
7 The device of claim 1, wherein the biological material is selected from the group comprising one or more of peptides, proteins, carbohydrates, nucleic acid molecules, lipids and other pharmaceutically active ingredients.
Dated this TH day of July, 2008 For Wockhardt Limited
(Mandar Kpdgule) AuthorizecrSignatory
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