Anti-Autoimmune Antibodies for Treatment of Pemphigus
AssigneeThe Trustees of the University of Pennsylvania
InventorsAimee S. Payne, John R. Stanley, Donald L. Siegel
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Abstract
This invention relates to compositions and methods for the use of anti-autoimmune reagents that specifically bind to anti-desmoglein antibodies, which are responsible for both pemphigus vulgaris and pemphigus foliaceus. In addition, the invention relates to methods and compositions for inhibiting the expression or function of a variable region of an anti-desmoglein (anti-Dsg) pathogenic autoantibody.
Claims81
An isolated anti-autoimmune reagent, wherein said anti-autoimmune reagent specifically binds to an anti-desmoglein autoantibody or fragment thereof.
An isolated nucleic acid sequence having at least 85% complementarity to a nucleic acid sequence selected from the group consisting of SEQ ID NOs:
- 1-73, and any combination thereof.
A method of inhibiting the binding of an anti-desmoglein autoantibody or fragment thereof to desmoglein, said method comprising contacting the anti-desmoglein autoantibody or fragment thereof with a composition comprising an anti-autoimmune reagent that specifically binds to an anti-desmoglein autoantibody or fragment thereof.
A method of modulating the expression of an anti-desmoglein autoantibody or fragment thereof, said method comprising contacting a nucleotide sequence encoding an anti-desmoglein autoantibody or fragment thereof with an inhibitor of an anti-desmoglein autoantibody or fragment thereof, wherein said inhibitor is capable of inhibiting the expression of said anti-desmoglein autoantibody or fragment thereof.
A method of treating an autoimmune pathology associated with desmoglein in a subject, the method comprising administering to a subject in need thereof a composition comprising an anti-autoimmune reagent that specifically binds to an anti-desmoglein autoantibody or fragment thereof, thereby inhibiting the binding of the anti-desmoglein autoantibody or fragment thereof to desmoglein.
A method of treating an autoimmune pathology associated with desmoglein in a subject, comprising contacting a nucleotide sequence of the subject encoding an anti-desmoglein autoantibody or fragment thereof with an inhibitor capable of inhibiting the expression of the nucleotide sequence encoding the anti-desmoglein autoantibody or fragment thereof;
- thereby inhibiting the expression of said anti-desmoglein autoantibody or fragment thereof.
A method of depleting a biological sample from an anti-desmoglein antibody or fragment thereof, said method comprising contacting the sample with an immobile composition comprising an anti-autoimmune reagent capable of specifically binding to an anti-desmoglein autoantibody or fragment thereof;
- and removing the biological sample without the bound anti-desmoglein autoantibody or fragment thereof, thereby depleting the biological sample of anti-desmoglein autoantibody or fragment thereof.
An isolated nucleic acid encoding an amino acid sequence selected from the group consisting of SEQ ID NOs:
- 170, 171, 172, 173, and any combination thereof.
An isolated peptide comprising an amino acid sequence selected from the group consisting of SEQ ID NOs:
- 170, 171, 172, 173, and any combination thereof.
An inhibitor capable of inhibiting the expression of an anti-desmoglein autoantibody or fragment thereof, wherein said inhibitor is capable of inhibiting the expression of a nucleic acid sequence as set forth in SEQ ID NOs:
- 1-73.
A method of diagnosing pemphigus in a subject, the method comprising contacting a biological sample of said subject with a composition comprising an anti-autoimmune reagent that specifically binds to an anti-desmoglein autoantibody or fragment thereof;
- and analyzing the biological sample for the presence of antibody-antigen complex, whereby the presence of antibody-antigen complex indicates the subject has or is predisposed to pemphigus.
An isolated antibody or fragment thereof comprising a consensus sequence, wherein said consensus sequence comprises the sequence represented by Asp-X-X-X-Trp (SEQ ID NO:
- 181) or Glu-X-X-X-Trp (SEQ ID NO:182).
A composition comprising a peptide, wherein said peptide comprises the amino acid sequence selected from the group consisting of SEQ ID NOs:
- 170, 171, 172, 173, and any combination thereof.
A method of treating an autoimmune disorder in a subject, said method comprising administering to a subject in need thereof an effective amount of a therapeutic composition comprising an anti-autoimmune reagent capable of binding to an antibody or fragment thereof present on the cell surface of a B cell, wherein said antibody or fragment thereof comprises the sequence represented by Asp-X-X-X-Trp (SEQ ID NO:
- 181), or Glu-X-X-X-Trp (SEQ ID NO:
- 182).
A method of contacting a B cell with a therapeutic moiety, wherein said B cell produces a disease-associated antibody, said method comprising contacting said B cell with a composition comprising an anti-autoimmune reagent capable of binding to an antibody or fragment thereof present on the cell surface of said B cell, wherein said anti-autoimmune reagent is conjugated or fused to a therapeutic moiety, thereby contacting said B cell with a therapeutic moiety.
The method of claim 79, wherein said disease-associated antibody comprises the amino acid sequence selected from the group consisting of SEQ ID NOs:
- 74-146, and any combination thereof.
A method of identifying a molecule capable of binding to an antibody or fragment thereof, said method comprising screening a library, wherein said screening comprises providing a library comprising a plurality of molecule members, contacting said antibody or fragment thereof with said library, and isolating those bound molecules which are bound by said antibody or fragment thereof, wherein the bound molecules being molecules that are capable of binding to said antibody or fragment thereof, thereby identifying a molecule capable of binding to an antibody or fragment thereof.
Dependencies are inferred from the claim text.