Hemoglobins as drug delivery agents
AssigneeSomatogen, Inc.
InventorsDavid C. Anderson, Antony James Mathews
Life of this patent
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Abstract
The invention relates to methods and compositions for delivering drugs to the body by binding them to hemoglobin. This technique stabilizes the drug and extends its half-life in the body. The drug may be chemically coupled to or adsorbed on the hemoglobin chain(s). Therapeutics are preferably linked to an artificial hemoglobin via a cysteine located deep within a cleft in the hemoglobin molecule.
Claims97
A conjugate of (a) a drug of interest, other than albumin, and (b) a hemoglobin-like protein,
- where said conjugate (1) has a therapeutic activity, as a conjugate, which is attributable to said drug, and/or (2) is capable of releasing said drug in therapeutically active form under physiological conditions,
- and where at least one of the following conditions applies:
- (I) the hemoglobin-like protein is not identical to human hemoglobin A.sub.O or human hemoglobin S, or
- (II) the drug of interest
- (a) is not ethacrynic acid, bezafibrate, succinyl-L-tryptophan-L-tryptophan, p-bromobenzyloxyacetic acid, or polyethylene glycol or
- (b) is bound through a disulfide to a cysteine residue of the hemoglobin-like protein.
A method for the prophylaxis or treatment of a disease or condition of a human or animal subject which comprises administering to said subject an amount, effective for prophylaxis or treatment of said disease or condition, of a conjugate of (a) a drug of interest, other than albumin, and (b) a hemoglobin-like protein, where said conjugate (1) has a therapeutic activity, as a conjugate, which is attributable to said drug, and/or (2) is capable of releasing said drug in therapeutically active form under physiological conditions,
- and where at least one of the following conditions applies:
- (I) the hemoglobin-like protein is not identical to human hemoglobin A.sub.o or human hemoglobin S, or
- (II) the drug of interest (a) is not ethacrynic acid, bezafibrate, succinyl-L-tryptophan-L-tryptophan, p-bromobenzyloxacetic acid, or polyethylene glycol;
- or (b) is bound through a disulfide to a cysteine residue of the hemoglobin-like protein.
A conjugate of (a) a drug of interest, and (b) a hemoglobin-related protein which comprises two or more domains each at least 75% identical in amino acid sequence with a wild-type human alpha globin and two or more domains each at least 75% identical in amino acid sequence with a wild-type human beta globin, where said hemoglobin-related protein does not bind oxygen.
A method for the prophylaxis or treatment of a disease or condition of a human or animal subject which comprises administering to said subject an amount, effective for prophylaxis or treatment of said disease or condition, of a conjugate of (a) a drug of interest, other than albumin, and (b) a hemoglobin-like protein, where said conjugate (1)has a therapeutic activity, as a conjugate, which is attributable to said drug, and/or (2) is capable of releasing said drug in therapeutically active form under physiological conditions.
Dependencies are inferred from the claim text.