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Recombinant antibody fragments for targeted treatment of autoimmune skin disease

Recombinant antibodies for diagnosis, treatment, and targeted drug delivery in skin disease.

Technology Overview:

Bullous pemphigoid (BP) is an autoantibody-mediated blistering skin disease in which the epidermal cells lose adhesion to the basement membrane. Patients feature circulating and tissue-bound autoantibodies that target two basement membrane proteins: BP180 (collagen XVII) and BP230, which when bound to the autoantibody activate an inflammatory cascade and blistering.

BP patients are currently treated using corticosteroids and immunosuppressants, however, more targeted therapies are needed in light of undesirable secondary effects from these medications. These effects are particularly adverse for the majority of BP patients who are elderly.

To overcome therapeutic constraints, more than 30 recombinant single chain variable fragment (scFv) antibodies have been generated, targeting BP180 and BP230. These antibody fragments lack the pathogenic characteristics of human-produced “full” autoantibodies. These non-pathogenic scFvs can be used in diagnostic and therapeutic applications for BP and many other skin diseases.

For example, the recombinant scFvs are capable of displacing patient antibodies that have previously bound to BP180, suggesting that the scFvs could be used alone as therapy. Additionally, the recombinant scFvs can be attached to disease-modifying drugs to provide skin-targeted therapeutic relief not only in BP, but also in many other diseases of the skin.

Advantages:

  • Non-pathogenic version of the full autoantibody
  • Easy to produce with high yields
  • Can be combined with other disease-modifying molecules

Applications:

  • Therapeutic through displacement of pathogenic, full serum autoantibodies that are bound to BP180 in patients
  • Drug delivery tool to the basement membrane of the zone of the skin and mucous membranes
  • Specific diagnosis of BP with differentiation from the related disease, pemphigus vulgaris, and research use

 

In bullous pemphigoid (BP), autoantibodies target the basement membrane proteins BP180 and BP230 (top) activating an inflammatory cascade that leads to skin blistering (bottom).

Stage of Development:

Developed and tested in a human skin organ culture model

Intellectual Property:

PCT patent application

Reference Media:

Desired Partnerships:

  • License
  • Co-development

Patent Information:

Inventors:

Docket # 18-8523

For Information, Contact:

Viviane Martin
University of Pennsylvania
215-746-4275
martinv@upenn.edu

Keywords