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Home Gene Therapy N-terminally-chemically-modified-protein-compositions-and-methods

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 N-terminally chemically modified protein compositions and methods

Details
Inventors: Gabriel, Nancy E.; Farrar, Christine E.;
Assignee: Amgen, Inc. (Thousand Oaks, CA)
Primary Examiner: Chism; B. Dell
Assistant Examiner:
Attorney, Agent or Firm: Marshall, Gerstein & Borun LLP

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.

DETAILED DESCRIPTION What is claimed is: 1.
A preparation comprising a predominant amount of a monopolymer/protein conjugate prepared from a hematopoietic protein having one or more available epsilon amino reactive groups, wherein the monopolymer/protein conjugate has a polyethylene glycol polymer moiety located at the N-terminus but not on an epsilon amino group, and the polyethylene glycol polymer moiety is conjugated via an alpha amino group and, wherein the monopolymer/protein conjugate has a prolonged in vivo biological activity relative to the non-conjugated hematopoietic protein.
2.
The preparation of claim 1 wherein the preparation comprises greater than 80% monopolymer/protein conjugate.
3.
The preparation of claim 1 wherein the preparation comprises at least 90% monopolymer/protein conjugate.
4.
The preparation of claim 1 wherein the preparation comprises greater than 95% monopolymer/protein conjugate.
5.
The preparation of claim 1 wherein the preparation comprises at least 99% monopolymer/protein conjugate.
6.
A preparation of a monopegylated hematopoietic protein prepared from a hematopoietic protein having one or more available epsilon amino reactive groups, wherein a polyethylene glycol polymer moiety is conjugated predominantly at the N-terminus of the hematopoietic protein and is conjugated via an alpha amino group and wherein the monopegylated hematopoietic protein has a prolonged in vivo biological activity relative to the non-conjugated hematopoietic protein.
7.
The hematopoietic protein preparation of claim 1 or 6 wherein the polyethylene glycol has a molecular weight of between about 2 kDa and about 100 kDa.
8.
The hematopoietic protein preparation of claim 7 wherein the polyethylene glycol has a molecular weight of about 6 kDa.
9.
The hematopoietic protein preparation of claim 7 wherein the polyethylene glycol has a molecular weight of about 12 kDa.
10.
The hematopoietic protein preparation of claim 7 wherein the polyethylene glycol has a molecular weight of about 20 kDa



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