Pulmonary administration of therapeutic proteins using an immunoglobulin transport pathway.
We have applied a "physiologic" approach to the pulmonary delivery of therapeutic proteins, utilizing an immunoglobulin (antibody) transport pathway recently shown to be present predominantly in the conducting airways of the human respiratory tract. Therapeutic proteins are fused to the Fc-domain of an IgG1, allowing them to bind with high affinity to the antibody transport receptor, FcRn. Liquid aerosols are administered into the lung using normal breathing maneuvers and efficient delivery of several different Fc-fusion proteins has been achieved with retention of biological activity and an increase in circulating half-life. A new paradigm for the pulmonary delivery of therapeutic proteins and a fundamental advance in the construction of Fc-fusion proteins for this purpose will be described.
Bitonti
Alan J
AJ
Syntonix Pharmaceuticals, 9 Fourth Avenue, Waltham, MA 02451, USA. abitonti@syntnx.com
Dumont
Jennifer A
JA
D000280:Administration, Inhalation; D000818:Animals; D016503:Drug Delivery Systems / Q000379:methods*; D006801:Humans; D007141:Immunoglobulin Fc Fragments / Q000008:administration & dosage*; D008168:Lung / Q000378:metabolism*; D004364:Pharmaceutical Preparations / Q000008:administration & dosage*; D011961:Receptors, Fc / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage*
D007141:Immunoglobulin Fc Fragments; D004364:Pharmaceutical Preparations; D011961:Receptors, Fc; D011993:Recombinant Fusion Proteins