Patent ID: 8080254
Filing Date: 2011-12-20
Classification: A61K,C07K

Abstract:
1. A protein having a formula selected from the group consisting of: R 1 -R 2 and R 1 -L-R 2 , wherein: R (a) amino acids 1-233 of SEQ ID NO: 9, amino acids 1-233 of SEQ ID NO: 12, amino acids 1-228 of SEQ ID NO: 15, or amino acids 1-228 of SEQ ID NO: 18; (b) the amino acid sequence of subpart (a) having a different amino acid substituted or deleted in one or more of the following positions (using the numbering according to SEQ. ID. NO. 9): (c) the amino acid sequence of subparts (a) or (b) having a methionyl residue at the N-terminus; (d) the amino acid sequence of subparts (a) through (c) wherein the Fc protein is connected to a water soluble polymer moiety selected from the group consisting of: polyethylene glycol, an ethylene glycol/propylene glycol copolymer, a carboxymethylcellulose, a dextran, a polyvinyl alcohol, a polyvinyl pyrolidone, a poly-1,3-dioxolane, a poly-1,3,6-trioxane, an ethylene/maleic anhydride copolymer, a polyaminoacid homopolymer, a polyaminoacid random copolymer, an albumin, a polylysine moiety, a poly(n-vinyl pyrolidone)polyethylene glycol, a propylene glycol homopolymer, a polypropylene oxide/ethylene oxide copolymer, a polyoxyethylated polyol, a polyethylene glycol propionaldehyde, a succinate, and a styrene; (e) the amino acid sequence of subpart (d) wherein said water soluble polymer moiety is polyethylene glycol; (f) the amino acid sequence of subpart (d) wherein said water soluble polymer is a polyamino acid-selected from the group consisting of an albumin, and a polylysine moiety; and (g) the amino acid sequence of subpart (d) wherein said water soluble polymer moiety is attached at solely the N-terminus of said Fc protein; R (A) the amino acid sequence 1-146 as set forth in SEQ. ID. NO. 3 or SEQ. ID. NO. 6; (B) the amino acid sequence 1-146 as set forth in SEQ. ID. NO. 6 having a lysine residue at position 35 and an isoleucine residue at position 74; (C) the amino acid sequence of subpart (B) wherein one or more of the following positions (using the numbering according to SEQ. ID. NO. 6): 4, 8, 32, 33, 35, 48, 50, 53, 60, 64, 66, 67, 68, 71, 74, 77, 78, 89, 97, 100, 102, 105, 106, 107, 108, 111, 112, 118, 136, 138, 142, and 145; is substituted with the corresponding amino acid at the corresponding position as set forth in SEQ ID NO: 3; (D) the amino acid sequence of subpart (B) wherein one or more of the following positions (using the numbering according to SEQ. ID. NO. 6) is substituted according to the following: (i) the amino acid at position 8 replaced with a serine; (ii) the amino acid at position 35 replaced with an arginine; (iii) the amino acid at position 48 replaced with a valine; (iv) the amino acid at position 53 replaced with a glutamine; (v) the amino acid at position 60 replaced with an isoleucine; (vi) the amino acid at position 66 replaced with an isoleucine; (vii) the amino acid at position 67 replaced with an asparagine; (viii) the amino acid at position 68 replaced with a leucine; (ix) the amino acid at position 89 replaced with a leucine; (x) the amino acid at position 100 replaced with a leucine; (xi) the amino acid at position 108 replaced with a glutamate; (xii) the amino acid at position 112 replaced with an aspartate; and (xiii) the amino acid at position 118 replaced with a leucine; (E) the amino acid sequence of subparts (A), (B), (C), or (D) optionally lacking a glutaminyl residue at position 28; (F) the amino acid sequence of subparts (A), (B), (C), (D), or (E) having a methionyl residue at the N-terminus, (G) the OB protein of subpart (A) through (F) wherein the OB protein comprises a water soluble polymer moiety selected from the group consisting of: polyethylene glycol, an ethylene glycol/propylene glycol copolymer, a carboxymethylcellulose, a dextran, a polyvinyl alcohol, a polyvinyl pyrolidone, a poly-1,3-dioxolane, a poly-1,3,6-trioxane, an ethylene/maleic anhydride copolymer, a polyaminoacid homopolymer, a polyaminoacid random copolymer, an albumin, a polylysine moiety, a poly(n-vinyl pyrolidone)polyethylene glycol, a propylene glycol homopolymer, a polypropylene oxide/ethylene oxide copolymer, a polyoxyethylated polyol, a polyethylene glycol propionaldehyde, a succinate, and a styrene; (H) the OB protein of subpart (G) wherein said water soluble polymer moiety is polyethylene glycol; (I) the OB protein of subpart (G) wherein said water soluble polymer is a polyamino acid selected from the group consisting of an albumin, and a polylysine moiety; and (J) the OB protein of subpart (G) wherein said water soluble polymer moiety is attached at solely the N-terminus of said OB protein; and L is a linker.