WO2016055403A1

WO2016055403A1 - Needle unit

Info

Publication number: WO2016055403A1
Application number: PCT/EP2015/072907
Authority: WO
Inventors: Marcus-Meinolf DITTRICH
Original assignee: Sanofi-Aventis Deutschland Gmbh
Priority date: 2014-10-06
Filing date: 2015-10-05
Publication date: 2016-04-14

Abstract

The invention relates to a needle unit (2) for connecting a drug delivery device to a medicament reservoir (1), the needle (2) unit comprising: - a hollow cannula (3) having a sharp proximal tip (3.1) for piercing a reservoir wall (1.1) of the medicament reservoir (1), - a stop member (5) which is axially fixed to the cannula (3), - a fluid pouch (4) disposed on a section of the cannula (3), - a fluid pump (8) for pumping a fluid through a fluid channel (7) into the fluid pouch (4), wherein in an initialstate the fluid pouch (4) is at least nearly flush with an outer surface of the cannula (3), wherein the fluid pouch (4) is adapted to dilate when the fluid is pumped into the fluid pouch (4) for squeezing the reservoir wall (1.1) between the stop member (5) and the fluid pouch (4).

Description

Needle unit Technical Field

The invention relates to a needle unit for connecting a drug delivery device to a medicament reservoir. Background of the Invention

A Drug delivery device may apply medicament reservoirs which need to be kept sterile prior to use and which may be connected to the drug delivery device by piercing a reservoir wall of the reservoir with a hollow needle. In particular with a flexible reservoir wall, it may be difficult to establish and maintain the connection between the needle and the reservoir.

Thus, there remains a need for an improved needle unit.

Summary of the Invention

It is an object of the present invention to provide an improved needle unit.

The object is achieved by a needle unit according to claim 1 . Exemplary embodiments of the invention are given in the dependent claims.

According to the invention, a needle unit for connecting a drug delivery device to a medicament reservoir comprises:

- a hollow cannula having a sharp proximal tip for piercing a reservoir wall of the medicament reservoir,

- a stop member which is axially fixed to the cannula,

- a fluid pouch disposed on a section of the cannula,

- a fluid pump for pumping a fluid through a fluid channel into the fluid pouch,

wherein in an initial state, the fluid pouch is at least nearly flush with an outer surface of the cannula, wherein the fluid pouch is adapted to dilate when the fluid is pumped into the fluid pouch for squeezing the reservoir wall between the stop member and the fluid pouch. Thus the position of the cannula within the reservoir is defined and can be reliably maintained. In an exemplary embodiment, the dilated fluid pouch is adapted to form a sealing area sealing the cannula against the reservoir wall to ensure that medicament held inside the medicament reservoir leaves the medicament reservoir only through the hollow cannula and does not leak out of the medicament reservoir outside of the cannula.

In an exemplary embodiment, the fluid channel is arranged within the stop member.

In an exemplary embodiment, the fluid pouch is fluidly connected to a fluid reservoir through the fluid channel and the fluid pump.

In an exemplary embodiment, the fluid pouch is integrally formed with the fluid channel. This renders the fluid pouch more leak proof. In an exemplary embodiment, one or more valves are arranged in series with the fluid pump for preventing fluid flow to and/or from the fluid pouch when the fluid pump is not active. Thus, the fluid pressure within the fluid pouch may be maintained after dilation without having to keep the fluid pump operating such that the reservoir wall remains held between the stop member and the dilated fluid pouch until the valve is operated to allow the fluid to flow out of the fluid pouch.

In an exemplary embodiment, the fluid pump is arranged to be switched to hold a predetermined pressure when having dilated the fluid pouch.

In an exemplary embodiment, a pressure sensor is arranged in the fluid channel between the fluid pouch and the fluid pump in order to detect, whether the pre-determined pressure has been reached such that the pump and/or the valve can be operated accordingly.

In an exemplary embodiment, the pressure sensor is connected to a control unit, wherein the control unit is adapted to stop operation of the drug delivery device when the pre-determined pressure is not reached during operation of the fluid pump. The pressure sensor may thus be used to detect leaks in the hydraulic system comprising the fluid pouch and the fluid channel. Stopping operation of the drug delivery device in this case may avoid harming a patient by injecting medicament contaminated with the fluid. In an exemplary embodiment, the cannula is double-walled with an inner wall and an outer wall, wherein a space is provided between the inner wall and the outer wall in which the fluid pouch is disposed prior to dilation, wherein one or more windows in the outer wall are provided to allow deployment of the fluid pouch. Thus, the fluid pouch does not protrude the surface of the cannula at all prior to being dilated. This may facilitate insertion of the cannula through the reservoir wall. In an exemplary embodiment, the fluid pouch comprises or consists of a bio compatible and/or drug compatible material, in particular polyvinyl chloride, cross-linked polyethylene,

polyethylene terephthalate or nylon. This prevents the fluid pouch from contaminating the medicament within the reservoir. Furthermore, these materials have the mechanical strength to withstand fluid pressure from within the fluid pouch.

In an exemplary embodiment, the stop member comprises or consist of a resilient rubber material or latex in order to be capable of forming a sealing surface against the reservoir wall and capable of forming a mechanical stop for limiting the extent of the cannula penetrating into the medicament reservoir.

In an exemplary embodiment, the fluid is a bio compatible and/or drug compatible medium and/or inert medium, in particular clean air, water, saline or the medicament held in the medicament reservoir. In an exemplary embodiment, the fluid pump fluidly connects the fluid pouch to a hollow channel within the cannula. This way, the medicament can be used as the fluid for dilating the fluid pouch. Hence, no additional fluid reservoir is needed and the risk for contamination of the medicament is reduced regardless of existing leaks. In an exemplary embodiment, the reservoir wall is flexible.

Further scope of applicability of the present invention will become apparent from the detailed description given hereinafter. However, it should be understood that the detailed description and specific examples, while indicating exemplary embodiments of the invention, are given by way of illustration only, since various changes and modifications within the spirit and scope of the invention will become apparent to those skilled in the art from this detailed description.

Brief Description of the Drawings

The present invention will become more fully understood from the detailed description given hereinbelow and the accompanying drawings which are given by way of illustration only, and thus, are not limitive of the present invention, and wherein: Figure 1 is a schematic view of an exemplary embodiment of a medicament reservoir with a needle unit having a fluid pouch,

Figure 2 is a schematic view of the medicament reservoir with the needle unit, wherein the fluid pouch is dilated,

Figure 3 is a schematic detail view of the medicament reservoir with the needle unit and the dilated fluid pouch, and

Figure 4 is a schematic view of another exemplary embodiment of a medicament

reservoir with a needle unit having a fluid pouch and a double walled cannula.

Corresponding parts are marked with the same reference symbols in all figures.

Detailed Description

Figure 1 is a schematic view of an exemplary embodiment of a medicament reservoir 1 with a needle unit 2. In an exemplary embodiment, the medicament reservoir 1 may have a flexible reservoir wall 1.1. The needle unit 2 comprises a hollow needle or cannula 3 for establishing a fluid connection between the medicament reservoir 1 and a drug delivery device (not shown). The longitudinal extension of the cannula 3 defines an axial direction. The cannula 3 comprises a sharp proximal tip 3.1 intended to pierce the reservoir wall 1 .1 of the medicament reservoir 1. The drug delivery device may comprise a medicament pump (not shown) for pumping a medicament from the medicament reservoir 1 through the cannula 3. Furthermore, the needle unit 2 comprises a fluid pouch 4 disposed on a section of the cannula 3. In an exemplary embodiment, the fluid pouch 4 may be glued to the cannula 3, e. g. at axial ends of the cannula 3. In an initial state as shown in figure 1 , the fluid pouch 4 is virtually flush with an outer surface of the cannula 3. The fluid pouch 4 may be circumferentially disposed about the section of the cannula 3.

The needle unit 2 further comprises a stop member 5 which is axially fixed to the cannula 3. The purpose of the stop member 5 is to limit movement of the needle unit 2 towards the medicament reservoir 1 when being attached to it. The stop member 5 may have a cylindrical form or any other form. In an exemplary embodiment a surface 5.1 of the stop member 5 facing the proximal tip 3.1 is shaped to allow for sealing the needle unit 2 against an outer surface of the reservoir wall 1.1 when the stop 5 is pushed against the reservoir wall 1 .1. Similar to an angioplasty balloon, the fluid pouch 4 dilates upon being subjected to a fluidic pressure built up inside the fluid pouch 4. For this purpose, the fluid pouch 4 is fluidly connected to a fluid reservoir 6 by a fluid channel 7 within and through the stop member 5 and by a fluid pump 8.

The fluid pouch 4 may be formed as a single piece with the fluid channel 7 extending through the stop member 5 and terminating at the fluid pump 8. This may render the fluid pouch 4 more leak proof.

In an exemplary embodiment, one or more valves 12 may be arranged in series with the fluid pump 8, the valves 12 preventing fluid flow to and/or from the fluid reservoir 6 when the fluid pump 8 is not active. In figure 1 , the needle unit 2 is partially deployed, i.e. the cannula 3 is inserted in the

medicament reservoir 1 through the reservoir wall 1.1. The sharp proximal tip 3.1 of the cannula 3 pierces the reservoir wall 1.1 when pushed against it. The cannula 3 is inserted into the medicament reservoir 1 to the point where the stop member 5 abuts the outer surface of the reservoir wall 1.1 . Subsequently, the fluid pump 8 is activated and starts pumping fluid from the fluid reservoir 6 through the fluid channel 7 into the fluid pouch 4 in order to deploy it.

Figure 2 is a schematic view of the medicament reservoir 1 with the needle unit 2, wherein the fluid pouch 4 is dilated due to the fluid pump 8 having pumped fluid from the fluid reservoir 6 into the fluid pouch 4 thereby expanding the fluid pouch 4 due to the displacement by the fluid. The fluid pouch 4 is dilated up to a point where it forms a second stop inside the medicament reservoir 1 for limiting movement of the needle unit 2 in the axial direction out of the

medicament reservoir 1 . The reservoir wall 1 .1 is thus squeezed between the stop member 5 and the fluid pouch 4. In an exemplary embodiment, the fluid pump 8 may be switched to a "hold pressure" state which can be established by controlling the pump action to hold the fluid pressure. For this purpose, a pressure sensor 9 may be arranged between the fluid pouch 4 and the fluid pump 8. Additionally or alternatively, a valve 12 may be disposed between the fluid pouch 4 and the fluid pump 8, the valve 12 adapted to prevent fluid flowing back from the fluid pouch 4 unless operated to do so. In an exemplary embodiment, the pressure sensor 9 may be used to detect leaks in the hydraulic system comprising the fluid pouch 4 and the fluid channel 7. If a p re-determined pressure is not reached during operation of the fluid pump 8 this may indicate a leak. A control unit 10 connected to the pressure sensor 9 may then decide to render the drug delivery device inoperable to remain in a safe state and avoid harming a patient.

Figure 3 is a schematic detail view of the medicament reservoir 1 with the needle unit 2 and the dilated fluid pouch 4. It can be seen that the dilated fluid pouch 4 forms a sealing area 1 1 to ensure that the medicament inside the medicament reservoir 1 leaves the medicament reservoir 1 only through the hollow cannula 3 and does not leak out of the medicament reservoir 1 outside of the cannula 3.

Figure 4 is a schematic view of an alternative exemplary embodiment of the needle unit 2, wherein the cannula 3 is double-walled with an inner wall 3.2 and an outer wall 3.3, wherein a space is provided between the inner wall 3.2 and the outer wall 3.3 in which the fluid pouch 4 is disposed prior to dilation. One or more windows 3.4 in the outer wall 3.3 allow deployment of the fluid pouch 4. In an exemplary embodiment the window 3.4 may be circumferentially arranged or only cover part of the circumference of the outer wall 3.3. In an exemplary embodiment, the cannula 3 comprises or consists of steel.

In an exemplary embodiment, the fluid pouch 4 comprises or consists of a bio compatible and/or drug compatible material which does not react with the medicament held in the medicament reservoir 1. For example, the fluid pouch 4 may be made from the same material as that used for balloon catheters which also has the mechanical strength to withstand fluid pressure from within the fluid pouch 4. For example, this material may be polyvinyl chloride, cross-linked polyethylene, polyethylene terephthalate or nylon.

The stop member 5 may comprise or consist of a resilient rubber material or latex that is capable of forming a sealing surface and capable of forming a mechanical stop for limiting the extent of the cannula 3 penetrating into the medicament reservoir 1.

In an exemplary embodiment, the fluid may be a bio compatible and/or drug compatible medium and/or inert medium that is in fluid form, e. g. clean air, water (injection grade), or saline. In an exemplary embodiment the medicament held in the medicament reservoir 1 may be used as the fluid for dilating the fluid pouch 4. In this case the fluid pump 8 may fluidly connect the fluid pouch 4 to the hollow channel within the cannula 3 instead of to a separate fluid reservoir 6. In order to reduce risk by potential leakage of the fluid, the fluid is one of the aforementioned liquids that are not harmful to a patient when injected unintentionally and in small amounts.

The needle unit 2 may be reusable.

The term "drug" or "medicament", as used herein, means a pharmaceutical formulation containing at least one pharmaceutically active compound, wherein in one embodiment the pharmaceutically active compound has a molecular weight up to 1500 Da and/or is a peptide, a proteine, a polysaccharide, a vaccine, a DNA, a RNA, an enzyme, an antibody or a fragment thereof, a hormone or an oligonucleotide, or a mixture of the above-mentioned pharmaceutically active compound, wherein in a further embodiment the pharmaceutically active compound is useful for the treatment and/or prophylaxis of diabetes mellitus or complications associated with diabetes mellitus such as diabetic retinopathy, thromboembolism disorders such as deep vein or pulmonary thromboembolism, acute coronary syndrome (ACS), angina, myocardial infarction, cancer, macular degeneration, inflammation, hay fever, atherosclerosis and/or rheumatoid arthritis, wherein in a further embodiment the pharmaceutically active compound comprises at least one peptide for the treatment and/or prophylaxis of diabetes mellitus or complications associated with diabetes mellitus such as diabetic retinopathy, wherein in a further embodiment the pharmaceutically active compound comprises at least one human insulin or a human insulin analogue or derivative, glucagon-like peptide (GLP-1 ) or an analogue or derivative thereof, or exendin-3 or exendin-4 or an analogue or derivative of exendin-3 or exendin-4. Insulin analogues are for example Gly(A21 ), Arg(B31 ), Arg(B32) human insulin; Lys(B3),

Glu(B29) human insulin; Lys(B28), Pro(B29) human insulin; Asp(B28) human insulin; human insulin, wherein proline in position B28 is replaced by Asp, Lys, Leu, Val or Ala and wherein in position B29 Lys may be replaced by Pro; Ala(B26) human insulin; Des(B28-B30) human insulin; Des(B27) human insulin and Des(B30) human insulin.

Insulin derivates are for example B29-N-myristoyl-des(B30) human insulin; B29-N-palmitoyl- des(B30) human insulin; B29-N-myristoyl human insulin; B29-N-palmitoyl human insulin; B28-N- myristoyl LysB28ProB29 human insulin; B28-N-palmitoyl-LysB28ProB29 human insulin; B30-N- myristoyl-ThrB29LysB30 human insulin; B30-N-palmitoyl- ThrB29LysB30 human insulin; B29-N- (N-palmitoyl-Y-glutamyl)-des(B30) human insulin; B29-N-(N-lithocholyl-Y-glutamyl)-des(B30) human insulin; B29-N-(oo-carboxyheptadecanoyl)-des(B30) human insulin and Β29-Ν-(ω- carboxyheptadecanoyl) human insulin.

Exendin-4 for example means Exendin-4(1 -39), a peptide of the sequence H-His-Gly-Glu-Gly-

Thr-Phe-Thr-Ser-Asp-Leu-Ser-Lys-Gln-Met-Glu-Glu-Glu-Ala-Val-Arg-Leu-Phe-lle-Glu-Trp-Leu-

Lys-Asn-Gly-Gly-Pro-Ser-Ser-Gly-Ala-Pro-Pro-Pro-Ser-NH2.

Exendin-4 derivatives are for example selected from the following list of compounds:

H-(Lys)4-des Pro36, des Pro37 Exendin-4(1 -39)-NH2,

H-(Lys)5-des Pro36, des Pro37 Exendin-4(1 -39)-NH2,

des Pro36 Exendin-4(1 -39),

des Pro36 [Asp28] Exendin-4(1 -39),

des Pro36 [lsoAsp28] Exendin-4(1 -39),

des Pro36 [Met(0)14, Asp28] Exendin-4(1 -39),

des Pro36 [Met(0)14, lsoAsp28] Exendin-4(1 -39),

des Pro36 [Trp(02)25, Asp28] Exendin-4(1 -39),

des Pro36 [Trp(02)25, lsoAsp28] Exendin-4(1 -39),

des Pro36 [Met(0)14 Trp(02)25, Asp28] Exendin-4(1 -39),

des Pro36 [Met(0)14 Trp(02)25, lsoAsp28] Exendin-4(1 -39); or des Pro36 [Asp28] Exendin-4(1 -39),

des Pro36 [lsoAsp28] Exendin-4(1 -39),

des Pro36 [Met(0)14, Asp28] Exendin-4(1 -39),

des Pro36 [Met(0)14, lsoAsp28] Exendin-4(1 -39),

des Pro36 [Trp(02)25, Asp28] Exendin-4(1 -39),

des Pro36 [Trp(02)25, lsoAsp28] Exendin-4(1 -39),

des Pro36 [Met(0)14 Trp(02)25, Asp28] Exendin-4(1 -39),

des Pro36 [Met(0)14 Trp(02)25, lsoAsp28] Exendin-4(1 -39),

wherein the group -Lys6-NH2 may be bound to the C-terminus of the Exendin-4 derivative; or an Exendin-4 derivative of the sequence

des Pro36 Exendin-4(1 -39)-Lys6-NH2 (AVE0010), H-(Lys)6-des Pro36 [Asp28] Exendin-4(1 -39)-Lys6-NH2,

des Asp28 Pro36, Pro37, Pro38Exendin-4(1 -39)-NH2,

H-(Lys)6-des Pro36, Pro38 [Asp28] Exendin-4(1 -39)-NH2,

H-Asn-(Glu)5des Pro36, Pro37, Pro38 [Asp28] Exendin-4(1 -39)-NH2,

des Pro36, Pro37, Pro38 [Asp28] Exendin-4(1 -39)-(Lys)6-NH2,

H-(Lys)6-des Pro36, Pro37, Pro38 [Asp28] Exendin-4(1 -39)-(Lys)6-NH2,

H-Asn-(Glu)5-des Pro36, Pro37, Pro38 [Asp28] Exendin-4(1 -39)-(Lys)6-NH2,

H-(Lys)6-des Pro36 [Trp(02)25, Asp28] Exendin-4(1 -39)-Lys6-NH2,

H-des Asp28 Pro36, Pro37, Pro38 [Trp(02)25] Exendin-4(1 -39)-NH2,

H-(Lys)6-des Pro36, Pro37, Pro38 [Trp(02)25, Asp28] Exendin-4(1 -39)-NH2,

H-Asn-(Glu)5-des Pro36, Pro37, Pro38 [Trp(02)25, Asp28] Exendin-4(1 -39)-NH2,

des Pro36, Pro37, Pro38 [Trp(02)25, Asp28] Exendin-4(1 -39)-(Lys)6-NH2,

H-(Lys)6-des Pro36, Pro37, Pro38 [Trp(02)25, Asp28] Exendin-4(1 -39)-(Lys)6-NH2,

H-Asn-(Glu)5-des Pro36, Pro37, Pro38 [Trp(02)25, Asp28] Exendin-4(1 -39)-(Lys)6-NH2, H-(Lys)6-des Pro36 [Met(0)14, Asp28] Exendin-4(1 -39)-Lys6-NH2,

des Met(0)14 Asp28 Pro36, Pro37, Pro38 Exendin-4(1 -39)-NH2,

H-(Lys)6-desPro36, Pro37, Pro38 [Met(0)14, Asp28] Exendin-4(1 -39)-NH2,

H-Asn-(Glu)5-des Pro36, Pro37, Pro38 [Met(0)14, Asp28] Exendin-4(1 -39)-NH2,

des Pro36, Pro37, Pro38 [Met(0)14, Asp28] Exendin-4(1 -39)-(Lys)6-NH2,

H-(Lys)6-des Pro36, Pro37, Pro38 [Met(0)14, Asp28] Exendin-4(1 -39)-(Lys)6-NH2,

H-Asn-(Glu)5 des Pro36, Pro37, Pro38 [Met(0)14, Asp28] Exendin-4(1 -39)-(Lys)6-NH2,

H-Lys6-des Pro36 [Met(0)14, Trp(02)25, Asp28] Exendin-4(1 -39)-Lys6-NH2,

H-des Asp28 Pro36, Pro37, Pro38 [Met(0)14, Trp(02)25] Exendin-4(1 -39)-NH2,

H-(Lys)6-des Pro36, Pro37, Pro38 [Met(0)14, Asp28] Exendin-4(1 -39)-NH2,

H-Asn-(Glu)5-des Pro36, Pro37, Pro38 [Met(0)14, Trp(02)25, Asp28] Exendin-4(1 -39)-NH2, des Pro36, Pro37, Pro38 [Met(0)14, Trp(02)25, Asp28] Exendin-4(1 -39)-(Lys)6-NH2,

H-(Lys)6-des Pro36, Pro37, Pro38 [Met(0)14, Trp(02)25, Asp28] Exendin-4(S1 -39)-(Lys)6-NH2, H-Asn-(Glu)5-des Pro36, Pro37, Pro38 [Met(0)14, Trp(02)25, Asp28] Exendin-4(1 -39)-(Lys)6- NH2; or a pharmaceutically acceptable salt or solvate of any one of the afore-mentioned Exendin-4 derivative.

Hormones are for example hypophysis hormones or hypothalamus hormones or regulatory active peptides and their antagonists as listed in Rote Liste, ed. 2008, Chapter 50, such as Gonadotropine (Follitropin, Lutropin, Choriongonadotropin, Menotropin), Somatropine (Somatropin), Desmopressin, Terlipressin, Gonadorelin, Triptorelin, Leuprorelin, Buserelin, Nafarelin, Goserelin.

A polysaccharide is for example a glucosaminoglycane, a hyaluronic acid, a heparin, a low molecular weight heparin or an ultra low molecular weight heparin or a derivative thereof, or a sulphated, e.g. a poly-sulphated form of the above-mentioned polysaccharides, and/or a pharmaceutically acceptable salt thereof. An example of a pharmaceutically acceptable salt of a poly-sulphated low molecular weight heparin is enoxaparin sodium. Antibodies are globular plasma proteins (-150 kDa) that are also known as immunoglobulins which share a basic structure. As they have sugar chains added to amino acid residues, they are glycoproteins. The basic functional unit of each antibody is an immunoglobulin (Ig) monomer (containing only one Ig unit); secreted antibodies can also be dimeric with two Ig units as with IgA, tetrameric with four Ig units like teleost fish IgM, or pentameric with five Ig units, like mammalian IgM.

The Ig monomer is a "Y"-shaped molecule that consists of four polypeptide chains; two identical heavy chains and two identical light chains connected by disulfide bonds between cysteine residues. Each heavy chain is about 440 amino acids long; each light chain is about 220 amino acids long. Heavy and light chains each contain intrachain disulfide bonds which stabilize their folding. Each chain is composed of structural domains called Ig domains. These domains contain about 70-1 10 amino acids and are classified into different categories (for example, variable or V, and constant or C) according to their size and function. They have a characteristic immunoglobulin fold in which two β sheets create a "sandwich" shape, held together by interactions between conserved cysteines and other charged amino acids.

There are five types of mammalian Ig heavy chain denoted by α, δ, ε, γ, and μ. The type of heavy chain present defines the isotype of antibody; these chains are found in IgA, IgD, IgE, IgG, and IgM antibodies, respectively.

Distinct heavy chains differ in size and composition; a and γ contain approximately 450 amino acids and δ approximately 500 amino acids, while μ and ε have approximately 550 amino acids. Each heavy chain has two regions, the constant region (C_H) and the variable region (V_H). In one species, the constant region is essentially identical in all antibodies of the same isotype, but differs in antibodies of different isotypes. Heavy chains γ, a and δ have a constant region composed of three tandem Ig domains, and a hinge region for added flexibility; heavy chains μ and ε have a constant region composed of four immunoglobulin domains. The variable region of the heavy chain differs in antibodies produced by different B cells, but is the same for all antibodies produced by a single B cell or B cell clone. The variable region of each heavy chain is approximately 1 10 amino acids long and is composed of a single Ig domain. In mammals, there are two types of immunoglobulin light chain denoted by λ and κ. A light chain has two successive domains: one constant domain (CL) and one variable domain (VL). The approximate length of a light chain is 21 1 to 217 amino acids. Each antibody contains two light chains that are always identical; only one type of light chain, κ or λ, is present per antibody in mammals.

Although the general structure of all antibodies is very similar, the unique property of a given antibody is determined by the variable (V) regions, as detailed above. More specifically, variable loops, three each the light (VL) and three on the heavy (VH) chain, are responsible for binding to the antigen, i.e. for its antigen specificity. These loops are referred to as the Complementarity Determining Regions (CDRs). Because CDRs from both VH and VL domains contribute to the antigen-binding site, it is the combination of the heavy and the light chains, and not either alone, that determines the final antigen specificity.

An "antibody fragment" contains at least one antigen binding fragment as defined above, and exhibits essentially the same function and specificity as the complete antibody of which the fragment is derived from. Limited proteolytic digestion with papain cleaves the Ig prototype into three fragments. Two identical amino terminal fragments, each containing one entire L chain and about half an H chain, are the antigen binding fragments (Fab). The third fragment, similar in size but containing the carboxyl terminal half of both heavy chains with their interchain disulfide bond, is the crystalizable fragment (Fc). The Fc contains carbohydrates, complement- binding, and FcR-binding sites. Limited pepsin digestion yields a single F(ab')2 fragment containing both Fab pieces and the hinge region, including the H-H interchain disulfide bond. F(ab')2 is divalent for antigen binding. The disulfide bond of F(ab')2 may be cleaved in order to obtain Fab'. Moreover, the variable regions of the heavy and light chains can be fused together to form a single chain variable fragment (scFv).

Pharmaceutically acceptable salts are for example acid addition salts and basic salts. Acid addition salts are e.g. HCI or HBr salts. Basic salts are e.g. salts having a cation selected from alkali or alkaline, e.g. Na+, or K+, or Ca2+, or an ammonium ion N+(R1 )(R2)(R3)(R4), wherein R1 to R4 independently of each other mean: hydrogen, an optionally substituted C1 -C6-alkyl group, an optionally substituted C2-C6-alkenyl group, an optionally substituted C6-C10-aryl group, or an optionally substituted C6-C10-heteroaryl group. Further examples of pharmaceutically acceptable salts are described in "Remington's Pharmaceutical Sciences" 17. ed. Alfonso R. Gennaro (Ed.), Mark Publishing Company, Easton, Pa., U.S.A., 1985 and in Encyclopedia of Pharmaceutical Technology. Pharmaceutically acceptable solvates are for example hydrates.

Those of skill in the art will understand that modifications (additions and/or removals) of various components of the apparatuses, methods and/or systems and embodiments described herein may be made without departing from the full scope and spirit of the present invention, which encompass such modifications and any and all equivalents thereof.

List of References

1 medicament reservoir

1 .1 reservoir wall

2 needle unit

3 cannula

3.1 proximal tip

3.2 inner wall

3.3 outer wall

3.4 window

4 fluid pouch

5 stop member

5.1 surface

6 fluid reservoir

7 fluid channel

8 fluid pump

9 pressure sensor

10 control unit

1 1 sealing area

12 valve

Claims

1 . Needle unit (2) for connecting a drug delivery device to a medicament reservoir (1 ), the needle (2) unit comprising:

- a hollow cannula (3) having a sharp proximal tip (3.1 ) for piercing a reservoir wall (1.1 ) of the medicament reservoir (1 ),

- a stop member (5) which is axially fixed to the cannula (3),

- a fluid pouch (4) disposed on a section of the cannula (3),

- a fluid pump (8) for pumping a fluid through a fluid channel (7) into the fluid pouch (4), wherein in an initial state the fluid pouch (4) is at least nearly flush with an outer surface of the cannula (3), wherein the fluid pouch (4) is adapted to dilate when the fluid is pumped into the fluid pouch (4) for squeezing the reservoir wall (1 .1 ) between the stop member (5) and the fluid pouch (4).

2. Needle unit (2) according to claim 1 , wherein the dilated fluid pouch (4) is adapted to form a sealing area (1 1 ) sealing the cannula (3) against the reservoir wall (1 .1 ).

3. Needle unit (2) according to one of the claims 1 or 2, wherein the fluid channel (7) is arranged within the stop member (5).

4. Needle unit (2) according to any one of the preceding claims, wherein the fluid pouch (4) is fluidly connected to a fluid reservoir (6) through the fluid channel (7) and the fluid pump (8).

5. Needle unit (2) according to any one of the preceding claims, wherein the fluid pouch (4) is integrally formed with the fluid channel (7).

6. Needle unit (2) according to any one of the preceding claims, wherein one or more valves (12) are arranged in series with the fluid pump (8) for preventing fluid flow to and/or from the fluid pouch (4) when the fluid pump (8) is not active.

7. Needle unit (2) according to any one of the preceding claims, wherein the fluid pump (8) is arranged to be switched to hold a pre-determined pressure when having dilated the fluid pouch (4).

8. Needle unit (2) according to any one of the preceding claims, wherein a pressure sensor (9) is arranged in the fluid channel (7) between the fluid pouch (4) and the fluid pump (8).

9. Needle unit (2) according to claim 8, wherein the pressure sensor (9) is connected to a control unit (10), wherein the control unit (10) is adapted to stop operation of the drug delivery device when a pre-determined pressure is not reached during operation of the fluid pump (8).

10. Needle unit (2) according to any one of the preceding claims, wherein the cannula (3) is double-walled with an inner wall (3.2) and an outer wall (3.3), wherein a space is provided between the inner wall (3.2) and the outer wall (3.3) in which the fluid pouch (4) is disposed prior to dilation, wherein one or more windows (3.4) in the outer wall (3.3) are provided to allow deployment of the fluid pouch (4).

1 1 . Needle unit (2) according to any one of the preceding claims, wherein the fluid pouch (4) comprises or consists of a bio compatible and/or drug compatible material, in particular polyvinyl chloride, cross-linked polyethylene, polyethylene terephthalate or nylon.

12. Needle unit (2) according to any one of the preceding claims, wherein the stop member (5) comprises or consist of a resilient rubber material or latex.

13. Needle unit (2) according to any one of the preceding claims, wherein the fluid is a bio compatible and/or drug compatible medium and/or inert medium, in particular clean air, water, saline or a medicament held in the medicament reservoir (1 ).

14. Needle unit (2) according to claim 13, wherein the fluid pump (8) fluidly connects the fluid pouch (4) to a hollow channel within the cannula (3).

15. Needle unit (2) according to one of the preceding claims, wherein the reservoir wall (1 .1 ) is flexible.