US2009325880A1PendingUtilityA1

Tnf receptor-like molecules and uses thereof

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Assignee: AMGEN INCPriority: Sep 5, 2000Filed: Jun 19, 2009Published: Dec 31, 2009
Est. expirySep 5, 2020(expired)· nominal 20-yr term from priority
Inventors:Lars Eyde TheillRichard YehScott SilbigerGang YuGiorgio Senaldi
A61P 37/06A61P 37/02A61P 31/04A61P 29/00A61P 35/02A61P 19/02C12N 2799/021C07K 2319/00A61K 38/00A61P 1/04C07K 14/7151
63
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Claims

Abstract

Novel MK61 polypeptides and nucleic acid molecules encoding the same. The invention also provides vectors, host cells, selective binding agents, and methods for producing MK61 polypeptides. Also provided for are methods for the treatment, diagnosis, amelioration, or prevention of diseases with MK61 polypeptides.

Claims

exact text as granted — not AI-modified
1 - 13 . (canceled) 
     
     
         14 . An isolated polypeptide comprising the amino acid sequence set forth in SEQ ID NO:2, SEQ ID NO:4, SEQ ID NO:6, SEQ ID NO:8, SEQ ID NO:10, SEQ ID NO:12, SEQ ID NO:14, or SEQ ID NO:16. 
     
     
         15 . An isolated polypeptide comprising the amino acid sequence selected from the group consisting of:
 (a) an amino acid sequence comprising the mature form of the polypeptide set forth in SEQ ID NO:2, SEQ ID NO:4, SEQ ID NO:6, SEQ ID NO:8, SEQ ID NO:10, SEQ ID NO:12, SEQ ID NO:14, or SEQ ID NO:16, and optionally further comprising an amino-terminal methionine;   (b) an amino acid sequence for an ortholog of SEQ ID NO:2, SEQ ID NO:4, SEQ ID NO:6, SEQ ID NO:8, SEQ ID NO:10, SEQ ID NO:12, SEQ ID NO:14, or SEQ ID NO:16, wherein the ortholog has an activity of the polypeptide set forth in SEQ ID NO:2, SEQ ID NO:4, SEQ ID NO:6, SEQ ID NO:8, SEQ ID NO:10, SEQ ID NO:12, SEQ ID NO:14, or SEQ ID NO:16;   (c) an amino acid sequence that exhibits at least about 70 percent identity to the amino acid sequence of SEQ ID NO:2, SEQ ID NO:4, SEQ ID NO:6, SEQ ID NO:8, SEQ ID NO:10, SEQ ID NO:12, SEQ ID NO:14, or SEQ ID NO:16, wherein the encoded polypeptide has an activity of the polypeptide set forth in SEQ ID NO:2, SEQ ID NO:4, SEQ ID NO:6, SEQ ID NO:8, SEQ ID NO:10, SEQ ID NO:12, SEQ ID NO:14, or SEQ ID NO:16;   (d) a fragment of the amino acid sequence set forth in SEQ ID NO:2, SEQ ID NO:4, SEQ ID NO:6, SEQ ID NO:8, SEQ ID NO:10, SEQ ID NO:12, SEQ ID NO:14, or SEQ ID NO:16 comprising at least about 25 amino acid residues, wherein the encoded polypeptide has an activity of the polypeptide as set forth in SEQ ID NO:2, SEQ ID NO:4, SEQ ID NO:6, SEQ ID NO:8, SEQ ID NO:10, SEQ ID NO:12, SEQ ID NO:14, or SEQ ID NO:16; and   (e) an amino acid sequence for an allelic variant or splice variant of either the amino acid sequence set forth in SEQ ID NO:2, SEQ ID NO:4, SEQ ID NO:6, SEQ ID NO:8, SEQ ID NO:10, SEQ ID NO:12, SEQ ID NO:14, or SEQ ID NO:16, or at least one of (a)-(c) wherein the encoded polypeptide has an activity of the polypeptide set forth in SEQ ID NO:2, SEQ ID NO:4, SEQ ID NO:6, SEQ ID NO:8, SEQ ID NO:10, SEQ ID NO:12, SEQ ID NO:14, or SEQ ID NO:16.   
     
     
         16 . An isolated polypeptide comprising the amino acid sequence selected from the group consisting of:
 (a) the amino acid sequence set forth in SEQ ID NO:2, SEQ ID NO:4, SEQ ID NO:6, SEQ ID NO:8, SEQ ID NO:10, SEQ ID NO:12, SEQ ID NO:14, or SEQ ID NO:16 with at least one conservative amino acid substitution, wherein the encoded polypeptide has an activity of the polypeptide set forth in SEQ ID NO:2, SEQ ID NO:4, SEQ ID NO:6, SEQ ID NO:8, SEQ ID NO:10, SEQ ID NO:12, SEQ ID NO:14, or SEQ ID NO:16;   (b) the amino acid sequence set forth in SEQ ID NO:2, SEQ ID NO:4, SEQ ID NO:6, SEQ ID NO:8, SEQ ID NO:10, SEQ ID NO:12, SEQ ID NO:14, or SEQ ID NO:16 with at least one amino acid insertion, wherein the polypeptide has an activity of the polypeptide set forth in SEQ ID NO:2, SEQ ID NO:4, SEQ ID NO:6, SEQ ID NO:8, SEQ ID NO:10, SEQ ID NO:12, SEQ ID NO:14, or SEQ ID NO:16;   (c) the amino acid sequence set forth in SEQ ID NO:2, SEQ ID NO:4, SEQ ID NO:6, SEQ ID NO:8, SEQ ID NO:10, SEQ ID NO:12, SEQ ID NO:14, or SEQ ID NO:16 with at least one amino acid deletion, wherein the polypeptide has an activity of the polypeptide set forth in SEQ ID NO:2, SEQ ID NO:4, SEQ ID NO:6, SEQ ID NO:8, SEQ ID NO:10, SEQ ID NO:12, SEQ ID NO:14, or SEQ ID NO:16;   (d) the amino acid sequence set forth in SEQ ID NO: 2 which has a C- and/or N-terminal truncation, wherein the polypeptide has an activity of the polypeptide set forth in SEQ ID NO:2, SEQ ID NO:4, SEQ ID NO:6, SEQ ID NO:8, SEQ ID NO:10, SEQ ID NO:12, SEQ ID NO:14, or SEQ ID NO:16; and   (e) the amino acid sequence set forth in SEQ ID NO:2, SEQ ID NO:4, SEQ ID NO:6, SEQ ID NO:8, SEQ ID NO:10, SEQ ID NO:12, SEQ ID NO:14, or SEQ ID NO:16, with at least one modification selected from the group consisting of amino acid substitutions, amino acid insertions, amino acid deletions, C-terminal truncation, and N-terminal truncation, wherein the polypeptide has an activity of the polypeptide set forth in SEQ ID NO:2, SEQ ID NO:4, SEQ ID NO:6, SEQ ID NO:8, SEQ ID NO:10, SEQ ID NO:12, SEQ ID NO:14, or SEQ ID NO:16.   
     
     
         17 . A polypeptide comprising the amino acid sequence of  claims 15  or  16  wherein the amino acid at position 38 of SEQ ID NO: 2, 4, 6, 8, 10 or 12 is cysteine, serine or alanine. 
     
     
         18 . A polypeptide comprising the amino acid sequence of  claims 15  or  16  wherein the amino acid at position 39 of SEQ ID NO: 2, 4, 6, 8, 10 or 12 is cysteine, serine or alanine. 
     
     
         19 . A polypeptide comprising the amino acid sequence of  claims 15  or  16  wherein the amino acid at position 51 of SEQ ID NO: 2, 4, 6, 8, 10 or 12 is cysteine, serine or alanine. 
     
     
         20 . A polypeptide comprising the amino acid sequence of  claims 15  or  16  wherein the amino acid at position 60 of SEQ ID NO: 2, or 6 is cysteine, serine or alanine. 
     
     
         21 . A polypeptide comprising the amino acid sequence of  claims 15  or  16  wherein the amino acid at position 76 of SEQ ID NO: 2, or 6 is cysteine, serine or alanine. 
     
     
         22 . A polypeptide comprising the amino acid sequence of  claims 15  or  16  wherein the amino acid at position 41 of SEQ ID NO: 14 or 16 is cysteine, serine or alanine. 
     
     
         23 . A polypeptide comprising the amino acid sequence of  claims 15  or  16  wherein the amino acid at position 42 of SEQ ID NO: 14 or 16 is cysteine, serine or alanine. 
     
     
         24 . A polypeptide comprising the amino acid sequence of  claims 15  or  16  wherein the amino acid at position 54 of SEQ ID NO: 14 or 16 is cysteine, serine or alanine. 
     
     
         25 . A polypeptide comprising the amino acid sequence of  claims 15  or  16  wherein the amino acid at position 63 of SEQ ID NO: 14 or 16 is cysteine, serine or alanine. 
     
     
         26 . A polypeptide comprising the amino acid sequence of  claims 15  or  16  wherein the amino acid at position 79 of SEQ ID NO: 14 or 16 is cysteine, serine or alanine. 
     
     
         27 . A polypeptide comprising the amino acid sequence of  claims 15  or  16  wherein the amino acid at position 171 of SEQ ID NO: 2 is leucine, norleucine, isoleucine, valine, methionine, alanine or phenylalanine. 
     
     
         28 . A polypeptide comprising the amino acid sequence of  claims 15  or  16  wherein the amino acid at position 172 of SEQ ID NO: 2 is leucine, norleucine, isoleucine, valine, methionine, alanine or phenylalanine. 
     
     
         29 . A polypeptide comprising the amino acid sequence of  claims 15  or  16  wherein the amino acid at position 178 of SEQ ID NO: 14 or 16 is leucine, norleucine, isoleucine, valine, methionine, alanine or phenylalanine. 
     
     
         30 . A polypeptide comprising the amino acid sequence of  claims 15  or  16  wherein the amino acid at position 180 of SEQ ID NO: 14 or 16 is leucine, norleucine, isoleucine, valine, methionine, alanine or phenylalanine. 
     
     
         31 . (canceled) 
     
     
         32 . The isolated polypeptide according to  claim 15  wherein the percent identity is determined using a computer program selected from the group consisting of GAP, BLASTP, BLASTN, FASTA, BLASTA, BLASTX, BestFit and the Smith-Waterman algorithm. 
     
     
         33 - 54 . (canceled) 
     
     
         55 . A composition comprising the polypeptide of  claims 14 ,  15 , or  16  and a pharmaceutically acceptable formulation agent. 
     
     
         56 . (canceled) 
     
     
         57 . The composition of  claim 55  wherein the polypeptide comprises the mature form of the polypeptide as set forth in SEQ ID NO:2, SEQ ID NO:4, SEQ ID NO:6, SEQ ID NO:8, SEQ ID NO:10, SEQ ID NO:12, SEQ ID NO:14, or SEQ ID NO:16. 
     
     
         58 - 63 . (canceled) 
     
     
         64 . A polypeptide comprising the polypeptide of any of  claims 14 ,  15 , or  16  fused to a heterologous amino acid sequence. 
     
     
         65 . The fusion polypeptide of  claim 64  wherein the heterologous amino acid sequence is an IgG constant domain or fragment thereof. 
     
     
         66 . A fusion polypeptide comprising the amino acid sequence of SEQ ID NO: 36. 
     
     
         67 . A fusion polypeptide comprising the amino acid sequence of SEQ ID NO: 39. 
     
     
         68 - 93 . (canceled) 
     
     
         94 . An isolated polypeptide encoded by a nucleic acid molecule comprising a nucleotide sequence selected from the group consisting of: (a) the nucleotide sequence as set forth in SEQ ID NO:1, SEQ ID NO:7, or SEQ ID NO:11; (b) the MK61 coding portion of SEQ ID NO:1, SEQ ID NO:7, or SEQ ID NO:11; (c) a nucleotide sequence encoding the polypeptide as set forth in SEQ ID NO:2, SEQ ID NO:8, or SEQ ID NO:12; (d) a nucleotide sequence fully complementary to a, b or c. 
     
     
         95 . An isolated polypeptide encoded by the nucleic acid molecule comprising a nucleotide sequence encoding a polypeptide that exhibits at least 90 percent identity to the polypeptide set forth in SEQ ID NO:2, wherein the encoded polypeptide has at least 150 amino acid residues and has the immune-modulating activity of the polypeptide as set forth in SEQ ID NO:2. 
     
     
         96 . An isolated polypeptide encoded by the nucleic acid molecule according to  claim 95 , wherein the percent identity is determined using a computer program selected from the group consisting of GAP, BLASTP, BLASTN, FASTA, BLASTA, BLASTX, BestFit and the Smith-Waterman algorithm. 
     
     
         97 . An isolated polypeptide encoded by the nucleic acid molecule comprising a nucleotide sequence selected from the group consisting of: (a) a nucleotide sequence encoding a polypeptide set forth in SEQ ID NO:2, with a substitution of one to 20 conservative amino acids, wherein the polypeptide has the immune-modulating activity of the polypeptide set forth in SEQ ID NO:2; (b) a nucleotide sequence encoding a polypeptide set forth in SEQ ID NO:2, with an insertion of one to 20 amino acids, wherein the polypeptide has the immune-modulating activity of the polypeptide set forth in SEQ ID NO:2; (c) a nucleotide sequence encoding a polypeptide set forth in SEQ ID NO:2, with an internal deletion of one to 20 amino acids, wherein the polypeptide has the immune-modulating activity of the polypeptide set forth in SEQ ID NO:2; (d) a nucleotide sequence encoding a polypeptide set forth in SEQ ID NO:2, which has a C- and/or N-terminal truncation of one to 100 amino acids, wherein the polypeptide has the immune-modulating activity of the polypeptide set forth in SEQ ID NO:2; and (e) a nucleotide sequence encoding a polypeptide set forth in SEQ ID NO:2, with a modification of one to 20 amino acids selected from the group consisting of amino acid substitutions, amino acid insertions, amino acid deletions, C-terminal truncation, and N-terminal truncation wherein the polypeptide has the immune-modulating activity of the polypeptide set forth in SEQ ID NO:2.

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