IL-18 receptors
AssigneeImmunex Corporation
InventorsJohn E. Sims, Teresa L. Born
Life of this patent
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Abstract
A novel polypeptide that functions as an IL-18 receptor is disclosed. The receptor is multimeric and includes at least one AcPL polypeptide, or fragment thereof, and at least one IL-1Rrp1 polypeptide, or fraction thereof. The receptor binds IL-18 and finds use in inhibiting biological activities mediated by IL-18.
Claims7
An isolated nucleic acid comprising at least one first oligonucleotide encoding one first polypeptide that binds IL-18, linked to at least one second oligonucleotide encoding one second polypeptide, wherein said first oligonucleotide is a DNA selected from the group consisting of:
- a) DNA comprising the coding region of the nucleotide sequence presented in SEQ ID NO:3;
- b) DNA that is complementary to DNA capable of hybridizing to the DNA of (a) under highly stringent conditions (hybridization at 68° C. followed by washing in 0.1×SSC/0.1% SDS at 63-68° C.);
- and,
- c) DNA that encodes a polypeptide comprising the amino acid sequence presented in SEQ ID NO:4;
- and,
- wherein said second oligonucleotide is a DNA selected from the group consisting of:
- a′) DNA comprising the coding region of the nucleotide sequence presented in SEQ ID NO:1;
- b′) DNA that is complementary to DNA capable of hybridizing to the DNA of (a′) under highly stringent conditions (hybridization at 68° C. followed by washing in 0.1×SSC/0.1% SDS at 63-68° C.);
- and
- c′) DNA that encodes a polypeptide comprising the amino acid sequence presented in SEQ ID NO:2,
- wherein a protein encoded by said nucleic acid binds IL-18 with an affinity greater than that of the first polypeptide.
An isolated nucleic acid comprising at least one first oligonucleotide encoding one first polypeptide that binds IL-18, linked to at least one second oligonucleotide encoding one second polypeptide, wherein said first oligonucleotide is a DNA selected from the group consisting of:
- a) DNA encoding a polypeptide comprising amino acids y-329 of SEQ ID NO:4, wherein y represents an integer between and including 1 and 20;
- and
- b) DNA that is complementary to DNA capable of hybridizing to the DNA of a) under highly stringent conditions (hybridization at 68° C. followed by washing in 0.1×SSC/0.1% SDS at 63-68° C.);
- and,
- wherein said second oligonucleotide is a DNA selected from the group consisting of:
- a′) DNA encoding a polypeptide comprising amino acids x-356 of SEQ ID NO:2, wherein x is an integer between and including 1 and 15;
- and
- b′) DNA that is complementary to DNA capable of hybridizing to the DNA of a′) under highly stringent conditions (hybridization at 68° C. followed by washing in 0.1×SSC/0.1% SDS at 63-68° C.);
- wherein a protein encoded by said nucleic acid binds IL-18 with an affinity greater than that of the first polypeptide.
An isolated nucleic acid encoding a protein comprising at least one first polypeptide that binds IL-18 linked to at least one second polypeptide, wherein the second polypeptide comprises a polypeptide that is at least 80% identical to a polypeptide having amino acids x-356 of SEQ ID NO:2, wherein x is an integer between and including 1 and 15;
- and wherein the first polypeptide comprises a polypeptide that is at least 80% identical to a polypeptide having amino acids y-329 of SEQ ID NO:4, wherein y represents an integer between and including 1 and 20;
- and, further wherein the isolated protein binds IL-18 with an affinity greater than that of the first polypeptide alone.
A nucleic acid encoding a protein having a formula selected from the group consisting of:
- R1-L1:R2-L2, R2-L2:R1-L1, R1-L2:R2-L1, R2-L1:R1-L2, R1-L1:R2−-/R2-L2:R1-L1, and, R1-L2:R2-L1/R2-L1:R1-L2
- wherein L1 is an immunoglobulin heavy chain fragment;
- L2 is an immunoglobulin light chain fragment;:
- is a linkage between a heavy chain and light chain antibody region,/is a linkage between a light chain and a heavy chain antibody region;
- and
- wherein R2 binds IL-18 and is selected from the group consisting of:
- a) a polypeptide comprising amino acids y-329 of SEQ ID NO:4, wherein y represents an integer between and including 1 and 20;
- b) a polypeptide that is at least 90% identical to the polypeptide of a);
- and,
- c) a fragment of the polypeptide of a), wherein the fragment binds IL-18,
- wherein said R1 is selected from the group consisting of:
- a′) a polypeptide comprising amino acids x-356 of SEQ ID NO:2, wherein x represents an integer between and including 1 and 15;
- and
- b′) a polypeptide that is at least 90% identical to the polypeptide of a′);
- c′) a fragment of the polypeptide of a′) that, in the presence of the polypeptide of a) binds IL-18 with a greater affinity than the polypeptide of a) alone,
- and further wherein the protein binds IL-18 with an affinity greater than that of R2 alone.
A nucleic acid encoding a heterodimeric protein comprising a first fusion polypeptide and a second fusion polypeptide, the first fusion polypeptide comprising an antibody light chain polypeptide attached to the C-terminus of a soluble first polypeptide or a soluble second polypeptide, and the second fusion polypeptide comprising an antibody heavy chain polypeptide attached to the C-terminus of a soluble first polypeptide or of a soluble second polypeptide, wherein said first fusion polypeptide is linked to said second fusion polypeptide via disulfide bonds between the heavy chain and light chain polypeptides;
- and,
- wherein the soluble first polypeptide binds IL-18 and is selected from the group consisting of:
- a) polypeptides comprising amino acids y-329 of SEQ ID NO:4, wherein y represents an integer between and including 1 and 20;
- and,
- b) polypeptides comprising a fragment of a), wherein the fragment is capable of binding IL-18;
- and
- wherein the soluble second polypeptide is selected from the group consisting of:
- a′) polypeptides comprising amino acids x-356 of SEQ ID NO:2, wherein x represents an integer between and including 1 and 15;
- b′) a polypeptide comprising a fragment of a′);
- wherein the soluble first polypeptide in combination with the fragment of a′) binds IL-18 with an affinity greater than that of the soluble first polypeptide alone.
A nucleic acid encoding a protein having a formula selected from the group consisting of:
- R1-L1:R2−-L2, R2-L2:R1-L1, R1-L2:R2-L1, R2-L1:R1-L2, R1-L1:R2−-L2/R2-L2:R1-L1, and, R1-L2:R2-L1/R2-L1:R1-L2
- wherein L1 comprises an immunoglobulin heavy chain fragment;
- L2 comprises an immunoglobulin light chain fragment;
- R1 comprises a fragment of SEQ ID NO:2;
- R2 comprises a fragment of SEQ ID NO:4 that binds IL-18;:
- is a linkage between a heavy chain and light chain antibody region, and/is a linkage between a light chain and a heavy chain antibody region, and further wherein the protein binds IL-18 with higher affinity than that of R2 alone.
A nucleic acid encoding a protein comprising at least one first polypeptide linked to at least one second polypeptide wherein the first polypeptide comprises a fragment of amino acids 1-329 of SEQ ID NO:4 that binds IL-18 and the second polypeptide comprises a fragment of amino acids 1-356 of SEQ ID NO:2, wherein the protein binds IL-18 with a greater affinity than that of the first polypeptide alone.
Dependencies are inferred from the claim text.