N-terminally chemically modified protein compositions and methods
View Patent ↗Provided herein are methods and compositions relating to the attachment of water soluble polymers to proteins. Provided are novel methods for N-terminally modifying proteins or analogs thereof, and resultant compositions, including novel N-terminally chemically modified G-CSF compositions and related methods of preparation. Also provided is chemically modified consensus interferon.
1. A method of treating a hematopoietic disorder, wherein the hematopoietic disorder is a result of a reduced neutrophil count, comprising administering a therapeutically effective dose of a substantially homogeneous preparation of N-terminally monopegylated granulocyte colony stimulating factor (G-CSF) or an analog thereof pegylated via an amine linkage optionally in a pharmaceutically acceptable diluent, carrier, or adjuvant.
2. The method of claim 1 , wherein the hematopoietic disorder is a result of an infectious disease.
3. The method of claim 2 , wherein the infectious disease is a bacterial, viral, or fungal infectious disease.
4. The method of claim 2 , wherein the infectious disease is sepsis.
5. The method of claim 1 , wherein the hematopoietic disorder is a result of chemotherapy.
6. The method of claim 1 , wherein the hematopoietic disorder is a result of radiation therapy.
7. The method of claim 1 , wherein the hematopoietic disorder is severe chronic neutropenia or a leukemia.
8. The method of claim 1 , wherein the therapeutically effective dose is in a range of 0.01 μg/kg body weight to 100 μg/kg body weight.
9. The method of claim 1 , wherein the polyethylene glycol has a molecular weight of 2 kDa to 100 kDa.
10. The method of claim 9 , wherein the polyethylene glycol has a molecular weight of 6 kDa to 25 kDa.
11. The method of claim 10 , wherein the polyethylene glycol has a molecular weight of 20 kDa.
12. The method of claim 1 , wherein the preparation comprises at least 90% N-terminally-modified G-CSF or analog thereof and at most 10% unpegylated G-CSF or analog thereof.
13. The method of claim 12 , wherein the preparation comprises at least 95% N-terminally-modified G-CSF or analog thereof and at most 5% unpegylated G-CSF or analog thereof.
14. The method of claim 1 , wherein the G-CSF or analog thereof is not glycosylated.
15. The method of claim 1 , wherein the G-CSF or analog thereof has a methionine at the N-terminus.