Nucleic acids encoding truncated soluble tumor necrosis factor
AssigneeAmgen Inc.
InventorsEric Fisher, Carl Edwards, III, Gary Kieft
Life of this patent
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Abstract
Disclosed are novel proteins, referred to as tumor necrosis factor binding proteins, that modulate the activity of tumor necrosis factor. Also disclosed are processes for obtaining the tumor necrosis binding proteins by recombinant genetic engineering techniques.
Claims13
An isolated nucleic acid molecule encoding a truncated tumor necrosis factor receptor (sTNFR) polypeptide comprising amino acid residues 1-110, 1-109, 1-108, 1-107, 1-106, 1-105, 1-104, 1-103, 2-110, 2-109, 2-108, 2-107, 2-106, 2-105, 2-104, 2-103, 3-110, 3-109, 3-108, 3-107, 3-106, 3-105, 3-104, 3-103, 4-110, 4-109, 4-108, 4-107, 4-106, 4-105, 4-104, 4-103, 5-110, 5-109, 5-108, 5-107, 5-106, 5-105, 5-104, 5-103, 6-110, 6-109, 6-108, 6-107, 6-106, 6-105, 6-104, 6-103, 7-110, 7-109, 7-108, 7-107, 7-106, 7-105, 7-104, 7-103, 8-110, 8-109, 8-108, 8-107, 8-106, 8-105, 8-104, 8-103, 9-110, 9-109, 9-108, 9-107, 9-106, 9-105, 9-104, 9-103, 10-110, 10-109, 10-108, 10-107, 10-106, 10-105, 10-104, 10-103, 11-110, 11-109, 11-108, 11-107, 11-106, 11-105, 11-104, 11-103, 12-110, 12-109, 12-108, 12-107, 12-106, 12-105, 12-104, 12-103, 13-110, 13-109, 13-108, 13-107, 13-106, 13-105, 13-104, 13-103, 14-110, 14-109, 14-108, 14-107, 14-106, 14-105, 14-104, 14-103, 15-110, 15-109, 15-108, 15-107, 15-106, 15-105, 15-104, 15-103, 16-110, 16-109, 16-108, 16-107, 16-106, 16-105, 16-104, 16-103, 17-110, 17-109, 17-108, 17-107, 17-106, 17-105, 17-104, 17-103, 18-110, 18-109, 18-108, 18-107, 18-106, 18-105, 18-104, 18-103, 19-110, 19-109, 19-108, 19-107, 19-106, 19-105, 19-104, or 19-103 of SEQ ID NO:2;
- provided however, that when the encoded truncated sTNFR polypeptide comprises amino acid residues 3-110, 4-110, 5-110, 6-110, 7-110, 8-110, 9-110, 10-110, 11-110, 12-110, 13-110, 14-110, 15-110, 16-110, 17-110, 18-110, or 19-110 of SEQ ID NO:2, the polypeptide does not further comprise amino acid residues 111-161 of SEQ ID NO:2, or a portion of residues 111-161 of SEQ ID NO:2 that has a carboxy-terminal truncation;
- and optionally further comprising an amino terminal methionine.
An isolated nucleic acid molecule encoding a truncated sTNFR-I polypeptide
- wherein the sTNFR-I polypeptide does not comprise a portion of the third domain of sTNFR-I including amino acid residues 111-126 of SEQ ID NO:2 and does not comprise the fourth domain of sTNFR-I including amino acids 127-461 of SEQ ID NO:2;
- and
- wherein the sTNFR-I polypeptide comprises the amino acid sequence as set forth in SEQ ID NO:4, SEQ ID NO:6, SEQ ID NO:8, SEQ ID NO:12, SEQ ID NO:10, or SEQ ID NO:14.
An isolated nucleic acid molecule encoding a truncated sTNFR polypeptide comprising:
- (a) a nucleotide sequence
- (i) as set forth in SEQ ID NO:3;
- (ii) as set forth in SEQ ID NO:5;
- (iii) as set forth in SEQ ID NO:7;
- (iv) as set forth in SEQ ID NO:11;
- (v) as set forth in SEQ ID NO:9;
- (vi) as set forth in SEQ ID NO:13;
- (vii) that is a degenerate sequence of the nucleotide sequence of any of (i)-(vi);
- or
- (viii) that hybridizes to the complement of the nucleotide sequence of any of(i)-(vii) at 62-67° C. in a hybridization buffer comprising 4×SSC, followed by washing in 0.1×SSC at 62-67° C.;
- wherein the nucleic acid molecule does not comprise nucleotide residues 331-483 of SEQ ID NO:1, or a portion thereof;
- and
- wherein the nucleic acid molecule encodes a truncated sTNFR polypeptide having TNF inhibitory activity;
- (b) a nucleotide sequence encoding a truncated sTNFR polypeptide comprising amino acid residues 19-103 of SEQ ID NO:2 and having TNF inhibitory activity, wherein the sTNFR polypeptide does not comprise amino acid residues 111-161 of SEQ ID NO:2 or a portion of residues 111-161 of SEQ ID NO:2 that has a carboxy-terminal truncation;
- or
- (c) a nucleotide sequence that is complementary to the nucleotide sequence of either (a) or (b).
Dependencies are inferred from the claim text.