Macromolecular compositions that cross the blood-brain barrier and methods of use thereof
First Claim
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1. A fusion antibody that is capable of crossing a blood-brain barrier (BBB), wherein the fusion antibody comprises a first antibody and a second antibody, wherein(i) the first antibody is a dual domain single-chain antibody that is linked to a carboxy terminus of the second antibody, and the first antibody comprises a VH region and a VL region;
- (ii) the first antibody retains an average of at least about 20% of its activity, compared to its activity as a separate entity; and
(iii) the first antibody targets an endogenous BBB receptor transport system and the second antibody targets a pathological substance associated with a brain disorder or the first antibody targets a pathological substance associated with a brain disorder and the second antibody targets an endogenous BBB receptor transport system,and wherein the fusion antibody comprises an Fc region that enables crossing the BBB from brain to blood by binding to an Fc receptor.
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Abstract
The invention provides diagnostic and therapeutic macromolecular compositions that cross the blood-brain barrier, in some embodiments in both directions, while allowing their activity to remain substantially intact once across the barrier. Also provided are methods for using such compositions in the diagnosis or treatment of CNS disorders such as Alzheimer'"'"'s disease.
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22 Claims
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1. A fusion antibody that is capable of crossing a blood-brain barrier (BBB), wherein the fusion antibody comprises a first antibody and a second antibody, wherein
(i) the first antibody is a dual domain single-chain antibody that is linked to a carboxy terminus of the second antibody, and the first antibody comprises a VH region and a VL region; -
(ii) the first antibody retains an average of at least about 20% of its activity, compared to its activity as a separate entity; and (iii) the first antibody targets an endogenous BBB receptor transport system and the second antibody targets a pathological substance associated with a brain disorder or the first antibody targets a pathological substance associated with a brain disorder and the second antibody targets an endogenous BBB receptor transport system, and wherein the fusion antibody comprises an Fc region that enables crossing the BBB from brain to blood by binding to an Fc receptor. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22)
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Specification