Title:  Methods for the treatment of immunologically-mediated skin disorders

United States Patent:  6,328,978

Assignee:  Genesis Research & Development Corp. Ltd. (Parnell, NZ)

Filed:  June 2, 1999

Methods for the treatment of skin disorders, including psoriasis, atopic dermatitis, allergic contact dermatitis, alopecia areata and skin cancers are provided, such methods comprising administering a composition having antigenic and/or adjuvant properties. Compositions which may be usefully employed in the inventive methods include inactivated M. vaccae cells, delipidated and deglycolipidated M. vaccae cells, M. vaccae culture filtrate and compounds present in or derived therefrom, together with combinations of such compositions.

SUMMARY OF INVENTION

Briefly stated, the present invention provides methods for the treatment of the skin disorders, including psoriasis, atopic dermatitis, allergic contact dermatitis, alopecia areata, scleroderma and skin cancers, such methods comprising administering an immunotherapeutic composition which is believed to have antigenic and/or adjuvant properties. The immunotherapeutic compositions are preferably administered by intradermal injection.

In a first aspect, the inventive methods comprise administering one or more doses of a composition including a component selected from the group consisting of inactivated M. vaccae cells, delipidated and deglycolipidated M. vaccae cells, and components that are present in or derived from either M. vaccae cells or M. vaccae culture filtrate. Specific examples of components present in or derived from either M. vaccae cells or M. vaccae culture filtrate include polypeptides that comprise an immunogenic portion of an antigen, or a variant thereof, wherein the antigen includes a sequence selected from the group consisting of SEQ ID NOS: 1-4, 9-16, 18-21, 23, 25, 26, 28, 29, 44, 45, 47, 52-55, 63, 64, 70, 75, 89, 94, 98, 100-105, 109, 110, 112, 121, 124, 125, 134, 135, 140, 141, 143, 145, 147, 152, 154, 156, 158, 160, 165, 166, 170, 172, 174, 177, 178, 181, 182, 184, 186, 187, 192 and 194.

In a second aspect, the inventive methods comprise administering a first dose of an immunotherapeutic composition at a first point in time and administering a second dose of the composition at a second, subsequent, point in time. Preferably, the multiple doses are administered at intervals of about 2-4 weeks. In one embodiment, compositions which may be usefully employed in such methods comprise a component selected from the group consisting of inactivated M. vaccae cells, M. vaccae culture filtrate, delipidated and deglycolipidated M. vaccae cells, and constituents and combinations thereof. In a second embodiment, compositions for use in such methods comprise at least one compound which is present in or derived from either M. vaccae cells or M. vaccae culture filtrate. Examples of such compounds include polypeptides comprising an immunogenic portion of an antigen, or a variant thereof, wherein the antigen includes a sequence selected from the group consisting of SEQ ID NOS: 1-4, 9-16, 18-21, 23, 25, 26, 28, 29, 44, 45, 47, 52-55, 63, 64, 70, 75, 89, 94, 98, 100-105, 109, 110, 112, 121, 124, 125, 134, 135, 140, 141, 143, 145, 147, 152, 154, 156, 158, 160, 165, 166, 170, 172, 174, 177, 178, 181, 182, 184, 186, 187, 192 and 194.

Additional compositions which may be usefully employed in the inventive methods comprise a DNA molecule encoding one or more of the above polypeptides. Compositions comprising a fusion protein, wherein the fusion protein includes at least one of the above polypeptides, together with DNA molecules encoding such fusion proteins, may also be usefully employed in the methods of the present invention.

The compositions employed in the present invention may additionally include a non-specific immune response enhancer, or adjuvant. Such adjuvants may include M. vaccae culture filtrate, delipidated and deglycolipidated M. vaccae cells, or a polypeptide comprising an immunogenic portion of an antigen, or a variant thereof, wherein said antigen includes a sequence provided in SEQ ID NOS: 114, 117 or 118.

The present invention further provides a method for treating psoriasis in a patient comprising administering a composition including a component selected from the group consisting of: inactivated M. vaccae cells; and delipidated and deglycolipidated M. vaccae cells, wherein the patient has a PASI score of less than about 10 following treatment.

In yet further aspects, methods are provided for inhibiting a Th2 immune response, and for treating skin disorders that are caused, at least in part, by a Th2 immune response (for example, atopic dermatitis, allergic contact dermatitis, alopecia areata, skin disorders associated with systemic lupus erythematosus, and other antibody-mediated skin diseases) such methods comprising administering a composition comprising inactivated M. vaccae cells, or delipidated and deglycolipidated M. vaccae cells. Methods are also provided for stimulating the production of IL-10 and thereby inhibiting skin inflammation, such methods comprising administering a composition comprising a component selected from the group consisting of: inactivated M. vaccae cells, and delipidated and deglycolipidated M. vaccae cells (DD-M. vaccae cells).

Claim 1 of 9 Claims

We claim:

1. A method for inhibiting skin inflammation associated with a skin disorder selected from the group consisting of psoriasis atopic dermatitis; and allergic contact dermatitis, the method comprising administering a composition comprising delipidated and deglycolipidated Mycobacterium vaccae cells.

____________________________________________
If you want to learn more about this patent, please go directly to the U.S. Patent and Trademark Office Web site to access the full patent.