Compositions and methods for liver growth and liver protection
First Claim
1. A method for promoting liver growth in a subject, comprising administering to the subject an effective amount of a VEGFR modulating agent, wherein the liver mass of the subject is increased, wherein the VEGFR modulating agent is a Flt-1 agonist comprising a Flt-1 selective VEGF-variant (Flt-sel) that selectively binds to Flt-1, wherein the Flt-sel VEGF variant comprises one or more amino acid sequence substitutions selected from the group consisting of I43A, I46A, Q79A and I83A, wherein the numbers refer to the amino acid residue positions along the amino acid sequence of a native VEGF165.
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Abstract
The present invention provides pharmaceutical compositions and methods for liver proliferation and protection. Specifically useful are VEGFR modulating agents capable of promoting liver growth. Disclosed compositions and methods may be useful for promoting proliferation or treating pathological conditions in other organs of significant biological functions.
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Citations
49 Claims
- 1. A method for promoting liver growth in a subject, comprising administering to the subject an effective amount of a VEGFR modulating agent, wherein the liver mass of the subject is increased, wherein the VEGFR modulating agent is a Flt-1 agonist comprising a Flt-1 selective VEGF-variant (Flt-sel) that selectively binds to Flt-1, wherein the Flt-sel VEGF variant comprises one or more amino acid sequence substitutions selected from the group consisting of I43A, I46A, Q79A and I83A, wherein the numbers refer to the amino acid residue positions along the amino acid sequence of a native VEGF165.
- 11. A method of treating a pathological liver condition in a subject, comprising administering to the subject a VEGFR modulating agent in a manner effective to alleviate the pathological liver condition, wherein the liver condition is liver failure, hepatitis, liver cirrhosis, toxic liver damage, medicamentary liver damage, hepatic encephalopathy, hepatic coma or hepatic necrosis, wherein the VEGFR modulating agent is a Flt-1 agonist comprising a Flt-1 selective VEGF-variant (Flt-sel) that selectively binds to Flt-1, wherein the Flt-sel VEGF variant comprises one or more amino acid sequence substitutions selected from the group consisting of I43A, I46A, Q79A and I83A, wherein the numbers refer to the amino acid residue positions along the amino acid sequence of a native VEGF165.
- 21. A method for promoting hepatocyte proliferation in the liver of a subject, comprising administering to the subject a Flt-1 agonist, in a manner effective to promote hepatocyte proliferation, wherein the Flt-1 agonist comprises a Flt-1 selective VEGF variant (Flt-sel) that selectively binds to Flt-1, wherein the Flt-sel VEGF variant comprises one or more amino acid sequence substitutions selected from the group consisting of I43A, I46A, Q79A and I83A, wherein the numbers refer to the amino acid residue positions along the amino acid sequence of a native VEGF165.
- 32. A method for protecting liver from damage in a subject duet to exposure to a hepatotoxic agent, said method comprising administering to the subject a VEGFR modulating agent, wherein said VEGFR modulating agent effectively protects liver from damage, wherein said VEGFR modulating agent is a Flt-1 agonist comprising a Flt-1 selective VEGF variant (Fit-sel) that selectively binds Flt-1, wherein the Flt-sel VEGF variant comprises one or more amino acid sequence substitutions selected from the group consisting of I43A, I46A, Q79A and I83A, wherein the numbers refer to the amino acid residue positions along the amino acid sequence of a native VEGF165.
Specification