# US 2008/0187558 A1 · Allergen dosage form

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- Number: US 2008/0187558 A1
- Document ID: US20080187558A1
- Status: Published application
- Kind: A1
- Application number: 12/098,150
- Filed: 2008-04-04
- Published: 2008-08-07
- Earliest claimed: 2002-11-26
- Assignees: ALK-Abello A/S
- Inventors: Henrik H. Jacobi; Annette R. Lundegaard; Christain G. Houghton; Stig Aasmul-Olsen; Lise L. Maerkedahl; Jan S. Andersen; Kerry Mallindine; Owen J. Murray; Susan G. Banbury; Desmond Yik Teng Wong; Lisa M. Garrett; Michael Hall
- Web page: https://patentgrep.com/patent/US20080187558A1

## CPC

- A61K 9/006: {Oral mucosa, e.g. mucoadhesive forms, sublingual droplets; Buccal patches or films; Buccal sprays}
- A61J 1/035: {Blister-type containers (blisters in general B65D75/36)}
- A61K 9/0056: {Mouth soluble or dispersible forms; Suckable, eatable, chewable coherent forms; Forms rapidly disintegrating in the mouth; Lozenges; Lollipops; Bite capsules; Baked products; Baits or other oral forms for animals}
- A61K 9/19: lyophilised {, i.e. freeze-dried, solutions or dispersions (lyophilised products with subsequent particle size reduction A61K9/14; granules or pellets made by lyphilisation A61K9/1682; solid oral dosage forms made by lyophilisation A61K9/2095; lyophilisation additives A61K47/00)}
- A61K 9/2018: {Sugars, or sugar alcohols, e.g. lactose, mannitol; Derivatives thereof, e.g. polysorbates}
- A61K 9/2063: {Proteins, e.g. gelatin}
- A61K 9/2095: {Tabletting processes}
- A61K 9/7007: {Drug-containing films, membranes or sheets (A61K9/0041, A61K9/0043, A61K9/006, A61K9/0063 take precedence)}
- A61K 39/35: Allergens
- A61K 39/36: from pollen
- A61K 39/39: characterised by the immunostimulating additives, e.g. chemical adjuvants
- A61K 45/06: Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
- A61P 27/14: Decongestants or antiallergics
- A61P 37/04: Immunostimulants
- A61P 37/08: Antiallergic agents (antiasthmatic agents A61P11/06; ophthalmic antiallergics A61P27/14)
- B65D 75/327: {and forming several compartments}
- G01N 33/15: Medicinal preparations {; Physical properties thereof, e.g. dissolubility}
- G01N 33/94: involving narcotics {or drugs or pharmaceuticals, neurotransmitters or associated receptors}
- A61K 2039/542: {oral/gastrointestinal}
- A61K 2039/545: {characterised by the dose, timing or administration schedule}
- G01N 2800/24: Immunology or allergic disorders
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)
- A61J: CONTAINERS SPECIALLY ADAPTED FOR MEDICAL OR PHARMACEUTICAL PURPOSES; DEVICES OR METHODS SPECIALLY ADAPTED FOR BRINGING PHARMACEUTICAL PRODUCTS INTO PARTICULAR PHYSICAL OR ADMINISTERING FORMS; DEVICES FOR ADMINISTERING FOOD OR MEDICINES ORALLY; BABY COMFORTERS; DEVICES FOR RECEIVING SPITTLE
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- B65D: CONTAINERS FOR STORAGE OR TRANSPORT OF ARTICLES OR MATERIALS, e.g. BAGS, BARRELS, BOTTLES, BOXES, CANS, CARTONS, CRATES, DRUMS, JARS, TANKS, HOPPERS, FORWARDING CONTAINERS; ACCESSORIES, CLOSURES, OR FITTINGS THEREFOR; PACKAGING ELEMENTS; PACKAGES
- G01N: INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES (measuring or testing apparatus or processes other than immunoassay, involving enzymes or microorganisms C12M, C12Q)

## Abstract

The invention provides allergen containing pharmaceutical products and in particular fast-dispersing solid allergen dosage forms. In particular, fast-dispersing, non-compressed solid dosage forms suitable for oromucosal administration comprising a matrix and at least one allergen are provided. Suitable matrices are gelatine, starch and mannitol. Methods for the dosage forms are also provided.

## Claims

### Claim 1

A pharmaceutical product suitable for administration of allergen comprising
a fast-dispersing, non-compressed solid dosage form suitable for oromucosal administration including:
(a) a matrix formed from at least one matrix-forming agent, and
(b) an effective dose of an allergen for desensitizing an individual to said allergen,
wherein
(c) the loss of the allergen content in said dosage form is less than 50% of the initial allergen content after being held for 3 months at 25° C. and 60% relative humidity, and
(d) the loss of allergen content from said solid dosage form is less than about 0.5 μg allergen extract or less than about 0.05 μg major allergen when subjected to a friability test.

### Claim 2 (depends on 1)

A pharmaceutical product according to claim 1, wherein one matrix-forming agent is gelatine.

### Claim 3 (depends on 2)

A pharmaceutical product according to claim 2, wherein the gelatine comprises fish gelatine.

### Claim 4 (depends on 3)

A pharmaceutical product according to claim 3, wherein a further matrix-forming agent is mannitol.

### Claim 5 (depends on 4)

A pharmaceutical product according to claim 4, wherein the ratio of fish gelatine to mannitol is from about 2:20 to about 20:1.

### Claim 6 (depends on 5)

A pharmaceutical product according to claim 5, wherein the ratio of fish gelatine to mannitol is from about 2:10 to about 10:1.

### Claim 7 (depends on 6)

A pharmaceutical product according to claim 6, wherein the ratio of fish gelatine to mannitol is from about 3:5.5 to about 6.5:3.

### Claim 8 (depends on 7)

A pharmaceutical product according to claim 7, wherein the ratio of fish gelatine to mannitol is 4:3.

### Claim 9 (depends on 7)

A pharmaceutical product according to claim 7, wherein the ratio of fish gelatine to mannitol is s 6.5:5.5.

### Claim 10 (depends on 7)

A pharmaceutical product according to claim 7, wherein the ratio of fish gelatine to mannitol is 6.0:5.08.

### Claim 11 (depends on 1)

A method of treating allergy or alleviating symptoms of allergy comprising oromucosal administration of the pharmaceutical product of claim 1.

### Claim 12

A method of producing a fast-dispersing, non-compressed solid and stable dosage form having low friability, comprising at least one matrix forming agent and being suitable for oromucosal administration comprising an effective dose for desensitizing an individual to at least one allergen, comprising the steps of
(a) preparing an aqueous solution comprising said at least one allergen and said at least one matrix forming agent,
(b) introducing the solution into one or more depressions in a mould
(c) subjecting the loaded mould to freezing and freeze-drying using standard conditions of shelf temperature and chamber pressure to obtain said solid dosage form in each depression.

### Claim 13 (depends on 1)

A method of measuring the friability of a solid dosage form as defined in claim 1 comprising the following steps;
(a) placing individual sealed blisters each containing a solid dosage form in equipment suitable for friability measurements;
(b) moving the sealed blister containing the solid dosage form for an appropriate time and at an appropriate velocity;
(c) removing the sealed blister containing the solid dosage form;
(d) opening the blister and placing the solid dosage form and any residues in a container;
(e) removing the solid dosage form from the container leaving any loose residuals in said container;
(f) performing an allergen specific assay on said residues determining the allergen content in said residues; and optionally calculating the percentage allergen content in said residues of the total allergen content of the solid dosage form unit.

### Claim 14

A pharmaceutical product suitable for oromucosal administration to a mammal, said product being a fast-dispersing solid dosage form comprising:
a matrix suitable for fast-dispersion upon oromucosal administration; and
an allergen in an amount sufficient to induce an allergen specific immune response to said allergen in said mammal.

### Claim 15 (depends on 14)

The pharmaceutical product of claim 14 wherein said allergen comprises an allergen extract.

### Claim 16 (depends on 14)

The pharmaceutical product of claim 14 wherein said allergen comprises a recombinant allergen.

### Claim 17 (depends on 14)

The pharmaceutical product of claim 14 without an adjuvant.

### Claim 18 (depends on 14)

The pharmaceutical product of claim 14 having a potency of about 65 to about 17,600 Biological Allergen Units (BAU).

### Claim 19 (depends on 14)

The pharmaceutical product of claim 14 having a potency of about 650 to about 3,500 Biological Allergen Units (BAU).

### Claim 20 (depends on 15)

The pharmaceutical product of claim 15 comprising from about 2.5 μg to about 3.75 mg allergen extract.

### Claim 21 (depends on 15)

The pharmaceutical product of claim 15 comprising from about 25 μg to about 0.75 mg allergen extract.

### Claim 22 (depends on 14)

The pharmaceutical product of claim 14 wherein the allergen comprises a major allergen in an amount from about 0.25 μg to about 375 μg.

### Claim 23 (depends on 14)

The pharmaceutical product of claim 14 wherein the allergen comprises a major allergen in an amount from about 2.5 μg to about 75 μg.

### Claim 24 (depends on 14)

The pharmaceutical product of claim 14 wherein the allergen comprises a major grass pollen allergen.

### Claim 25 (depends on 24)

The pharmaceutical product of claim 24 comprising from about 2.5 μg to about 75 μg of a major grass pollen allergen selected from the group consisting of grass group 1 allergen, grass group 5 allergen and grass group 6 allergen.

### Claim 26 (depends on 14)

The pharmaceutical product of claim 14 wherein the matrix and allergen are in a solid, non-compressed form.

### Claim 27 (depends on 24)

The pharmaceutical product of claim 24 wherein the product has a disintegration time of less than 5 seconds.

### Claim 28 (depends on 24)

The pharmaceutical product of claim 24 wherein the product is not coated.

### Claim 29 (depends on 14)

The pharmaceutical product of claim 14 wherein the matrix comprises non-mammalian gelatin.

### Claim 30 (depends on 14)

The pharmaceutical product of claim 14 wherein the matrix comprises fish gelatin.

### Claim 31 (depends on 25)

A multiple dose set of pharmaceutical products according to claim 25, each dose containing the same amount of allergen.

### Claim 32 (depends on 14)

A multiple dose set of pharmaceutical products according to claim 14, each dose containing the same amount of allergen.

### Claim 33

A method for inducing an allergen specific immune response in a mammal, comprising oromucosal administration of a fast-dispersing solid pharmaceutical product that comprises
a matrix suitable for fast-dispersion upon oromucosal administration; and
an allergen in an amount sufficient to induce an allergen specific immune response to said allergen in said mammal, wherein said pharmaceutical product is provided in its own separate container or compartment.

### Claim 34 (depends on 33)

The method of claim 33 wherein said allergen comprises an allergen extract.

### Claim 35 (depends on 33)

The method of claim 33 wherein said allergen comprises a recombinant allergen.

### Claim 36 (depends on 33)

The method of claim 33 comprising oromucosal administration of a plurality of said pharmaceutical products.

### Claim 37 (depends on 33)

The method of claim 33 wherein the product has a potency of about 65 to about 17,600 Biological Allergen Units (BAU).

### Claim 38 (depends on 33)

The method of claim 33 wherein the product has a potency of about 650 to about 3,500 Biological Allergen Units (BAU).

### Claim 39 (depends on 34)

The method of claim 34 wherein the allergen comprises from about 2.5 μg to about 3.75 mg of allergen extract.

### Claim 40 (depends on 34)

The method of claim 34 wherein the allergen comprises from about 25 μg to about 0.75 mg of allergen extract.

### Claim 41 (depends on 33)

The method of claim 33 wherein the allergen comprises a major allergen in an amount from about 0.25 μg to about 375 μg.

### Claim 42 (depends on 33)

The method of claim 33 wherein the allergen comprises a major allergen in an amount from about 2.5 μg to about 75 μg.

### Claim 43 (depends on 33)

The method of claim 33 wherein the allergen comprises a major grass pollen allergen.

### Claim 44 (depends on 43)

The method of claim 43 wherein the major grass pollen allergen is a member selected from the group consisting of group 1 allergen, group 5 allergen and group 6 allergen.

### Claim 45 (depends on 33)

The method of claim 33 wherein the product is in a solid, non-compressed form.

### Claim 46 (depends on 33)

The method of claim 33 wherein the product further comprises at least one anti-allergic drug.

### Claim 47 (depends on 33)

The method of claim 33 further comprising providing instructions concerning use of the product.

### Claim 48

A method for desensitizing a mammal to a major allergen or major allergens, comprising administering oromucosally to a mammal in need thereof a plurality of fast dispersing pharmaceutical products, each pharmaceutical product comprising substantially the same amount of at least one major allergen, wherein said amount is sufficient to induce an allergen specific immune response to said major allergen(s) in said mammal, and wherein each pharmaceutical product in the plurality is administered according to a schedule of treatment.

### Claim 49

A method for desensitizing a mammal to an allergen or allergens, comprising administering oromucosally to a mammal in need thereof a plurality of fast dispersing pharmaceutical products, each pharmaceutical product comprising substantially the same amount of an allergen extract, which is sufficient to induce an allergen specific immune response to at least one major allergen in said allergen extract in said mammal, and wherein each pharmaceutical product in the plurality is administered according to a schedule of treatment.

### Claim 50 (depends on 48)

The method of claim 48 wherein the product has a potency of about 65 to about 17,600 Biological Allergen Units (BAU).

### Claim 51 (depends on 49)

The method of claim 49 wherein the product comprises from about 2.5 μg to about 3.75 mg allergen extract.

### Claim 52 (depends on 50)

The method of claim 50 wherein the product has a potency of about 650 to about 3,500 Biological Allergen Units (BAU).

### Claim 53 (depends on 48)

The method of claim 48 wherein the pharmaceutical products are substantially free of an additive that functions as an adjuvant when said products are administered to the mammal.

### Claim 54 (depends on 48)

The method of claim 48 wherein the at least one major allergen is a major grass pollen allergen.

### Claim 55 (depends on 48)

The method of claim 48 wherein the product is in a non-compressed form and the product is not coated.

### Claim 56 (depends on 48)

The method of claim 48 wherein the product comprises non-bovine gelatin.

### Claim 57 (depends on 48)

The method of claim 48 wherein the product comprises non-mammalian gelatin.

### Claim 58 (depends on 48)

The method of claim 48 wherein the product comprises fish gelatin.

### Claim 59 (depends on 48)

The method of claim 48 wherein the product further comprises an anti-allergic drug.

### Claim 60

A pharmaceutical product for desensitizing a mammal to a major allergen or major allergens, comprising a fast-dispersing solid dosage form suitable for oromucosal administration, the dosage form comprising a matrix suitable for fast-dispersion and further comprising an effective dose of at least one major allergen, the product inducing an allergen specific immune response to said major allergen(s) in the absence of an added adjuvant.

### Claim 61 (depends on 60)

The pharmaceutical product of claim 60 further comprising an additive that functions as an adjuvant when the product is administered to the mammal.

### Claim 62

A method for treating grass pollen allergy in a mammal which comprises:
orally administering to said mammal an oral dosage form containing a predetermined effective dose of a major grass pollen allergen for desensitization of said mammal to grass pollen and
repeating the administration of the same predetermined effective dose at least once daily.

### Claim 63 (depends on 62)

The method of claim 62 wherein said effective dose of said major grass pollen allergen has a potency of about 65 to about 17,600 BAU.

### Claim 64 (depends on 63)

The method of claim 63 wherein said major grass pollen allergen is a member selected from the group consisting of grass group 1 allergen, grass group 5 allergen and grass group 6 allergen.

### Claim 65 (depends on 64)

The method of claim 64 wherein said dosage form comprises from about 2.5 μg to about 75 μg of said major grass pollen allergen.

### Claim 66 (depends on 63)

The method of claim 63 wherein said dosage form comprises non-mammalian gelatin.

### Claim 67

A method for treatment of an allergy which comprises:
orally administering to a mammal in need of such treatment an oral dosage form containing a predetermined effective dose of an allergen for desensitization to said allergy, and
repeatedly administering the same predetermined effective dose to said mammal.

### Claim 68 (depends on 67)

The method of claim 67 wherein said administering step comprises administering said dosage form at least once per day.

### Claim 69 (depends on 68)

The method of claim 68 wherein said dose has a potency of about 65 to about 17,600 Biological Allergen Units (BAU).

### Claim 70 (depends on 68)

The method of claim 68 wherein said oral dosage form comprises non-mammalian gelatin.

### Claim 71 (depends on 69)

The method of claim 69 which comprises continuing said daily administration until the symptoms of said allergy in said mammal are relieved.

### Claim 72

A kit for use in treating an allergy in a mammal which comprises:
a solid support,
a plurality of solid oral dosage forms, each of said solid oral dosage forms being held in a sealed enclosure on said support and each containing essentially the same effective dose of a major allergen for desensitizing said mammal to said major allergen.

### Claim 73 (depends on 72)

The kit of claim 72 wherein each of said oral dosage forms comprises non-mammalian gelatin.

### Claim 74 (depends on 72)

The kit of claim 72 wherein said oral dosage forms has a potency of about 65 and about 17,600 BAU.

### Claim 75 (depends on 72)

The kit of claim 72 wherein each of said oral dosage forms comprises between about 0.25 μg to about 375 μg of said major allergen.

### Claim 76 (depends on 72)

The kit of claim 72 wherein the major allergen is a grass pollen allergen.

### Claim 77 (depends on 77)

The kit of claim 77 wherein the grass pollen allergen comprises from about 0.25 μg to about 375 μg of a member selected from the group consisting of grass group 1 allergen, grass group 5 allergen and grass group 6 allergen.

### Claim 78 (depends on 72)

The kit of claim 72 wherein the major allergen is a dust mite allergen.