Back to results
US 2022/0031812 A1Published application
Chimeric Proteins and Methods of Use for Treatment of Central Nervous System Disorders
AssigneeSilver Creek Pharmaceuticals, Inc.
InventorsSamuel J. Pfaff, Yan Zhang, Kristopher M. Kuchenbecker, Lakhmir Chawla
Life of this patent
Estimating the term…
Abstract
Aspects of the present disclosure relate generally to kits and methods for treating acute central nervous systems disorders with chimeric proteins and pharmaceutical compositions comprising such chimeric proteins.
Claims20
A method of treating acute central nervous system injury, the method comprising administering by bolus injection to a subject in need thereof a pharmaceutical composition comprising a therapeutically effective amount of a chimeric protein and a pharmaceutically acceptable carrier,
- wherein the chimeric protein comprises (a) a targeting domain comprising a variant of human Annexin 5 (AnxV) comprising one or more mutations, wherein the one or more mutations consist of a substitution at the position corresponding to C316 and optionally at one or more positions corresponding to R63, K70, K101, E138, D139, N160, and combinations thereof;
- (b) an activator domain comprising a variant of human insulin-like growth factor IGF-1 comprising one or more mutations, wherein the one or more mutations consist of a substitution at one or more positions corresponding to E3, Y24, Y31, Y60, and combinations thereof, wherein the variant of IGF-1 decreases activation of the IGF-1 receptor relative to the wild-type IGF-1, and (c) a half-life modulator comprising a variant of human serum albumin (HSA) comprising one or more mutations, wherein the one or more mutations consist of a substitution at one or more positions corresponding to C58 and N527, and combinations thereof,
- wherein administration results in at least one of:
- mitigation of oxidative damage to cells of the cerebral cortex, repair or acceleration of repair of blood brain barrier, reduction of oedema, reduction of infarct volume, reduction of blood brain barrier permeability, targeted stimulation of the phosphorylation of serine/threonine protein kinase B (AKT) pathway by selective activation of the IGF-1 receptor in cells of injured brain tissue, targeted delivery of pro-survival signals to injured brain tissue, increase in musculoskeletal coordination following stroke, improvement to consciousness following stroke, improvement to neurologic function following stroke, and improvement in motor function following stroke.
1 more element
A kit for treating acute central nervous system injury, the kit comprising:
- (a) a plurality of individual containers, each individual container comprising a volume of a pharmaceutical composition comprising a therapeutically effective amount of a chimeric protein and a pharmaceutically acceptable carrier, wherein the pharmaceutical composition is formulated for bolus injection,
- wherein the chimeric protein comprises (i) a targeting domain comprising a variant of human Annexin 5 (AnxV) comprising one or more mutations, wherein the one or more mutations consist of a substitution at the position corresponding to C316 and optionally at one or more positions corresponding to R63, K70, K101, E138, D139, N160, and combinations thereof;
- (ii) an activator domain comprising a variant of human insulin-like growth factor IGF-1 comprising one or more mutations, wherein the one or more mutations consist of a substitution at one or more positions corresponding to E3, Y24, Y31, Y60, and combinations thereof, wherein the variant of IGF-1 decreases activation of the IGF-1 receptor relative to the wild-type IGF-1, and (iii) a half-life modulator comprising a variant of human serum albumin (HSA) comprising one or more mutations, wherein the one or more mutations consist of a substitution at one or more positions corresponding to C58 and N527, and combinations thereof,
- wherein each of the plurality of the individual containers comprises a volume ranging from about 1 ml to about 50 ml,
- wherein each of the plurality of the individual containers comprises an amount of chimeric protein ranging from about 20 mg to about 1,000 mg;
- and
- (b) instructions for use in treating acute central nervous system injury.
4 more elements
Dependencies are inferred from the claim text.