Anti-human transferrin receptor antibody permeating blood-brain barrier
Disclosed are a means to convert compounds having physiological or pharmacological activity and unable to pass through the blood-brain barrier into a form that allows them to pass through the blood-brain barrier, and compounds converted thereby. The means is an anti-human transferrin receptor antibody and the converted compounds are molecular conjugates between physiologically active protein or pharmacologically active low-molecular-weight compounds and an anti-human transferrin receptor antibody.
1. A fusion protein which penetrates the blood brain barrier following administration to a human comprising a humanized anti-human transferrin receptor (anti-hTfR) antibody amino acid sequence and a human iduronate 2-sulfatase amino acid sequence, wherein the fusion protein is selected from (1) to (3) below:
(1) the fusion protein, wherein the humanized anti-hTfR antibody light chain has the amino acid sequence set forth as SEQ ID NO:164, and wherein the humanized anti-hTfR antibody heavy chain is linked, on the C-terminal side thereof and via a linker sequence Gly-Ser, to the human iduronate 2-sulfatase, and the whole linked heavy chain has the amino acid sequence set forth as SEQ ID NO:247,
(2) the fusion protein, wherein the humanized anti-hTfR antibody light chain has the amino acid sequence set forth as SEQ ID NO:180, and wherein the humanized anti-hTfR antibody heavy chain is linked, on the C-terminal side thereof and via a linker sequence Gly-Ser, to the human iduronate 2-sulfatase, and the whole linked heavy chain has the amino acid sequence set forth as SEQ ID NO:249, and
(3) the fusion protein, wherein the humanized anti-hTfR antibody light chain has the amino acid sequence set forth as SEQ ID NO:196, and wherein the humanized anti-hTfR antibody heavy chain is linked, on the C-terminal side thereof and via a linker sequence Gly-Ser, to the human iduronate 2-sulfatase, and the whole linked heavy chain has the amino acid sequence set forth as SEQ ID NO:251.
2. A polynucleotide encoding the amino acid sequence of the fusion protein according to claim 1 .
3. An expression vector comprising the polynucleotide according to claim 2 that is incorporated therein.
4. A mammalian cell transformed with the expression vector according to claim 3 .
5. A method for the treatment of Hunter syndrome comprising parenterally administering a therapeutically effective amount of the fusion protein according to claim 1 to a patient with Hunter syndrome.
6. A pharmaceutical agent comprising the fusion protein according to claim 1 .