Antigen-binding proteins that inhibit superantigens for the treatment of skin diseases

• US 20110166076A1
• Filed: 09/10/2009
• Published: 07/07/2011
• Est. Priority Date: 09/10/2008
• Status: Abandoned Application

• Current Assignee: BAC IP BV (Perspecta, Inc.)
• Original Assignee: BAC IP BV (Perspecta, Inc.)
• Inventors: Maassen, Bram Theodorus Hendrikus, Adams, Hendrik
• Application Number:
  US13/063,363
• Publication Number:
  US 20110166076A1
• Time in Patent Office: Days
• US Class Current: 514/18.6
• CPC Class Codes: A61K 2039/505 comprising antibodies
• CPC Class Codes: A61P 17/00 Drugs for dermatological disorders
• CPC Class Codes: A61P 31/04 Antibacterial agents
• CPC Class Codes: C07K 16/1271 from Micrococcaceae (F), e.g. Staphylococcus
• CPC Class Codes: C07K 16/1275 from Streptococcus (G)
• CPC Class Codes: C07K 2317/22 from camelids, e.g. camel, llama or dromedary
• CPC Class Codes: C07K 2317/569 Single domain, e.g. dAb, sdAb, VHH, VNAR or nanobody®
• CPC Class Codes: C07K 2317/73 Inducing cell death, e.g. apoptosis, necrosis or inhibition of cell proliferation

Abstract

The present invention relates to superantigen-specificantigen-binding proteins comprising an immunoglobulin-derived variable domain that comprises a complete antigen binding site for an epitope on the superantigen in a single polypeptide chain. The antigen-binding proteins of the invention may be used in the treatment skin diseases. The antigen-binding proteins of the invention may be used in compositions for topical administration.

Claims

1. An antigen-binding protein for use in the treatment of a skin disease, wherein the antigen-binding protein is an inhibitor of a superantigen.

2. A method of treating a skin disease in a subject in need thereof comprising administering the antigen-binding protein of claim 1 in an amount effective to inhibit a superantigen.

3. An antigen-binding protein according to claim 1, wherein the antigen-binding protein is defined as an inhibitor of superantigen if in a tritium-thymidine incorporation assay on human PBMCs, after stimulation of the PBMCs with superantigen, the tritium activity incorporated in the PBMCs in counts per minute at a concentration of at least 34 nM of antigen-binding protein is less than 70% of the tritium activity in counts per minute in a control sample without antigen-binding protein, and preferably results in the tritium activity in counts per minute as incorporated in PBMCs without superantigen stimulation.

4. An antigen-binding protein according to claim 3, wherein the PBMCs are stimulated with 11.4 nM TSST-1, 1.8 nM SEA or 7.1 nM SEB.

5. An antigen-binding protein according to claim 1, wherein the superantigen is TSST-1.

6. An antigen-binding protein according to claim 1, wherein the antigen-binding protein comprises an immunoglobulin-derived variable domain that comprises a complete antigen binding site for an epitope on TSST-1 in a single polypeptide chain.

7. The method according to claim 2, wherein the skin disease is a micro-organism related skin disease, selected from the group consisting of atopic dermatitis, staphylococcal scalded skin syndrome, staphylococcal scarlatiniform eruption, guttate psoriasis, psoriasis vulgaris, cutaneous T-cell lymphoma, micro-organism-related eczema and acute juvenile pityriasis rubra pilaris.

8. An antigen-binding protein according to claim 1, wherein the antigen-binding protein comprises an amino acid sequence that comprises 4 framework regions, FR1 to FR4, and 3 complementarity determining regions, CDR1 to CDR3, that are operably linked in the order FR1-CDR1-FR2-CDR2-FR3-CDR3-FR4, wherein:

(a) the CDR1 has an amino acid sequence as presented in SEQ ID NO;

72 or an amino acid sequence that differs from SEQ ID NO;

72 in one or two of the amino acid residues;

(b) the CDR2 has an amino acid sequence having at least 80% sequence identity with an amino acid sequence as presented in SEQ ID NO;

139 and,

(c) the CDR3 is an amino acid sequence having at least 80% sequence identity with an amino acid sequence as presented in SEQ ID NO;

206 and,

wherein each of the framework regions has at least 50% amino acid identity with the framework amino acid sequence of any one of SEQ ID NO;

1-4.

9. An antigen-binding protein or a use according to claim 8, wherein the antigen-binding protein comprises an amino acid sequence which has at least 60% amino acid identity with the amino acid sequence as presented in SEQ ID NO:

5.

10. The method according to claim 2, wherein the treatment further comprises a conventional treatment of a skin disease, with corticosteroids.

11. The method according to claim 2, wherein the antigen-binding protein is administered topically in a formulation selected from the group consisting of liniments, lotions, creams, ointments or pastes, and drops suitable for administration to the eye, ear or nose.

12. An antigen-binding protein comprising an amino acid sequence that comprises 4 framework regions, FR1 to FR4, and 3 complementarity determining regions, CDR1 to CDR3, that are operably linked in the order FR1-CDR1-FR2-CDR2-FR3-CDR3-FR4, wherein:

(a) the CDR1 has an amino acid sequence as presented in SEQ ID NO;

72 or an amino acid sequence that differs from SEQ ID NO;

72 in one or two of the amino acid residues;

(b) the CDR2 has an amino acid sequence having at least 80% sequence identity with an amino acid sequence as presented in SEQ ID NO;

139; and

,

(c) the CDR3 is an amino acid sequence having at least 80% sequence identity with an amino acid sequence as presented in SEQ ID NO;

206; and

,

wherein each of the framework regions has at least 50% amino acid identity with the framework amino acid sequence of any one of SEQ ID NO;

1-4.

13. An antigen-binding protein according to claim 12, wherein the antigen-binding protein comprises an amino acid sequence which has at least 60% amino acid identity with the amino acid sequence as presented in SEQ ID NO:

5

15. A composition comprising an antigen-binding protein as defined in claim 12 and a pharmaceutically acceptable carrier, wherein the composition is formulated for topical administration.

14. (canceled)