Methods and compositions for treatment of symptoms associated with intracranial hemorrhage
View Patent ↗Methods and compositions are provided for the treatment of a patient with intracranial hemorrhage (ICH). Methods include the use of the products of recombinant constructs such as those that contain lactoferrin, as well as fusion protein constructs of lactoferrin and Fc domain for IgG.
1. A recombinant polypeptide comprising:
a lactoferrin sequence;
an immunoglobulin IgG2 Fc domain sequence fused to said lactoferrin sequence; and
an IgG2 hinge sequence, wherein said hinge is located between said lactoferrin sequence and said Fc domain sequence,
wherein the amino acid sequence of said recombinant polypeptide has a sequence of SEQ ID NO: 2.
2. The polypeptide of claim 1 , wherein the polypeptide is glycosylated to form a glycosylated polypeptide.
3. The polypeptide of claim 2 , wherein the glycosylated polypeptide is N-linked.
4. A composition comprising the polypeptide of claim 1 in a pharmaceutically acceptable carrier, wherein said carrier is aqueous, powder, or saline, and wherein said composition is frozen or lyophilized.
5. A method of treating or preventing intracranial hemorrhage or a related disorder in a subject, comprising administering to said subject an effective amount of a composition comprising the polypeptide of claim 1 , and wherein said polypeptide is administered intrathecally, buccally, orally, topically, intradermally, subcutaneously, intranasally, intramuscularly, intravenously, intra-arterially, or directly into a tissue site.
6. The method of claim 5 , wherein said related disorder is a cognitive or neurological deficit, inflammation, infection, edema or brain atrophy due to intracranial hemorrhage.
7. An isolated recombinant polynucleotide molecule comprising a coding sequence for a polypeptide comprising:
a lactoferrin coding sequence;
an immunoglobulin IgG2 Fc domain coding sequence fused to said lactoferrin coding sequence; and
an IgG2 hinge coding sequence, wherein said hinge is located between said lactoferrin coding sequence and said Fc domain coding sequence; and
wherein polypeptide has a sequence of SEQ ID NO: 2.
8. The polynucleotide of claim 7 , wherein the nucleic acid sequence of said polynucleotide comprises SEQ ID NO: 1.
9. An expression vector comprising a heterologous promoter sequence linked to a polynucleotide of claim 7 .
10. The expression vector of claim 9 , wherein said vector is expressed in a mammalian cell, a CHO cell, a yeast cell, or an insect cell.
11. A host cell, comprising a polynucleotide molecule of claim 7 .