INTERFERON LAMBDA-ANTIBODY COMPLEXES

摘要

The present invention concerns methods and compositions for forming complexes of interferon-λ with an antibody or antigen-binding antibody fragment. In preferred embodiments, the interferon-λ and the antibody or fragment are fusion proteins, each comprising a dimerization and docking domain (DDD) moiety from human protein kinase A or an anchor domain (AD) moiety from an A-kinase anchoring protein (AKAP). In more preferred embodiments, the interferon-antibody complex is more efficacious for treatment of cancer, asthma, Alzheimer's disease, multiple sclerosis or viral infection than interferon-λ alone, antibody alone, or the combination of unconjugated interferon-λ and antibody.

主权项

1. A method of treating cancer, a viral infection, asthma or multiple sclerosis comprising:
a) obtaining an interferon-antibody complex comprising;
i) a first fusion protein comprising human interferon-λ attached to an anchor domain (AD) moiety from an AKAP (A-kinase anchoring protein), wherein the amino acid sequence of the AD moiety is selected from the group consisting of SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO:10, SEQ ID NO:32, SEQ ID NO:33, SEQ ID NO:34, SEQ ID NO:35, SEQ ID NO:36, SEQ ID NO:37, SEQ ID NO:38, SEQ ID NO:39, SEQ ID NO:40, SEQ ID NO:41, SEQ ID NO:42, SEQ ID NO:43, SEQ ID NO:44, SEQ ID NO:45, SEQ ID NO:46, SEQ ID NO:47, SEQ ID NO:48, SEQ ID NO:49, SEQ ID NO:50, SEQ ID NO:51, SEQ ID NO:52, SEQ ID NO:53, SEQ ID NO:54, SEQ ID NO:55, SEQ ID NO:56, SEQ ID NO:57, SEQ ID NO:58, SEQ ID NO:59, SEQ ID NO:60, SEQ ID NO:61, SEQ ID NO:62, SEQ ID NO:63, SEQ ID NO:64, SEQ ID NO:65, SEQ ID NO:66, SEQ ID NO:67, SEQ ID NO:68, SEQ ID NO:69, SEQ ID NO:70, SEQ ID NO:71, SEQ ID NO:72, SEQ ID NO:73, SEQ ID NO:74, SEQ ID NO:75, SEQ ID NO:76, SEQ ID NO:77, SEQ ID NO:78, SEQ ID NO:79, SEQ ID NO:80, SEQ ID NO:81, SEQ ID NO:82, SEQ ID NO:83 and SEQ ID NO:84;ii) a second fusion protein comprising an antibody or antigen-binding antibody fragment attached to a dimerization and docking domain (DDD) moiety from human protein kinase A (PKA) RIIα; and b) administering the interferon-antibody complex to a subject with cancer, a viral infection, asthma or multiple sclerosis;wherein two copies of the DDD moiety form a dimer that binds to the AD moiety to form the complex.