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US 11,576,978 B2Granted
Hemoglobin-based therapeutic agents
AssigneeCheer Global Limited
InventorsSui-Yi Kwok, Norman Fung-Man Wai, Lan Zou
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Abstract
Provided herein are hemoglobin-based therapeutic agents useful for treating cancer, pharmaceutical composition including the same, and methods of use and preparation thereof.
Claims19
A hemoglobin-based therapeutic agent comprising a hemoglobin and a chemotherapeutic agent selected from the group consisting of maytansinoid, an auristatin, and a calicheamicin, wherein the chemotherapeutic agent is covalently attached to the hemoglobin via a linker, and wherein the linker has the Formula 1:
- the linker has the Formula 2:
- wherein A is the chemotherapeutic;
- N* represents a nitrogen in a lysine side chain in the hemoglobin or a N-terminal amine in the hemoglobin;
- S* represents a sulfur in a cysteine side chain in the hemoglobin;
- n is a whole number selected from 1-10;
- and
- each R is hydrogen;
- or two R taken together with the carbons to which they are attached form a 3-7 membered cycloalkane and each remaining R is hydrogen.
5 more elements
A method for preparing a hemoglobin-based therapeutic agent of Formula 3:
- wherein A is DM1 or DM4;
- X is the MDR of the hemoglobin-based therapeutic agent, wherein X has a value between 1.0-5.0;
- N* independently represents a nitrogen in a lysine side chain in the hemoglobin or a N-terminal amine in the hemoglobin;
- n is a whole number selected from 1-10;
- and
- each R is hydrogen;
- or two R taken together with the carbons to which they are attached form a 3-7 membered cycloalkane and each remaining R is hydrogen, the method comprising:
- contacting a hemoglobin with a compound of Formula 4:
- wherein LG is a leaving group, thereby forming the hemoglobin-based therapeutic agent of Formula 3.
6 more elements
Dependencies are inferred from the claim text.