C3b/C4b complement receptor-like molecules and uses thereof

Abstract

Novel C3b/C4b CR-like polypeptides and nucleic acid molecules encoding the same. The invention also provides vectors, host cells, selective binding agents, and methods for producing C3b/C4b CR-like polypeptides. Also provided for are methods for the treatment, diagnosis, amelioration, or prevention of diseases with C3b/C4b CR-like polypeptides.

1 - 56 . (canceled)  
     
     
         57 . An antibody produced by immunizing an animal with a polypeptide comprising the amino acid sequence of SEQ ID NO: 2.  
     
     
         58 . An antibody or fragment thereof that specifically binds to a polypeptide comprising the amino acid sequence of SEQ ID NO: 2.  
     
     
         59 . An antibody or fragment thereof that specifically binds to a polypeptide encoded by a nucleic acid sequence selected from the group consisting of: 
 (a) a nucleotide sequence set forth in SEQ ID NO: 1;    (b) a nucleotide sequence encoding the polypeptide as set forth in SEQ ID NO: 2; and    (c) a nucleotide sequence which hybridizes under stringent conditions to the complement of (a) or (b), wherein said stringent conditions comprise a final wash at 65° C. in 0.1×SSC and 0.1% SDS, wherein the nucleotide sequence encodes a polypeptide which has C3b/C4b complement receptor-like activity of the polypeptide set forth in SEQ ID NO: 2.    
     
     
         60 . The antibody or fragment thereof of any one of claims  57 - 59  that is a human antibody or fragment thereof.  
     
     
         61 . The antibody or fragment thereof of any one of claims  57 - 59  that is a humanized antibody or fragment thereof.  
     
     
         62 . The antibody or fragment thereof of any one of claims  57 - 59  that is a polyclonal antibody or fragment thereof.  
     
     
         63 . The antibody or fragment thereof of any one of claims  57 - 59  that is a monoclonal antibody or fragment thereof.  
     
     
         64 . A hybridoma that produces the monoclonal antibody or fragment thereof of  claim 63 .  
     
     
         65 . A derivative of the antibody of any one of claims  57 - 59 .  
     
     
         66 . The derivative of  claim 65  which is covalently modified with a water-soluble polymer.  
     
     
         67 . The derivative of  claim 66  wherein the water-soluble polymer is selected from the group consisting of polyethylene glycol, monomethoxy-polyethylene glycol, dextran, cellulose, poly-(N-vinyl pyrrolidone) polyethylene glycol, propylene glycol homopolymers, polypropylene oxide/ethylene oxide co-polymers, polyoxyethylated polyols, and polyvinyl alcohol.  
     
     
         68 . An isolated nucleic acid molecule comprising a nucleotide sequence that encodes a soluble polypeptide that comprises a fragment of the amino acid sequence of SEQ ID NO: 2 and has C3b/C4b complement receptor-like activity of the polypeptide set forth in SEQ ID NO: 2.  
     
     
         69 . The nucleic acid molecule of  claim 68 , wherein the encoded soluble polypeptide lacks a transmembrane or a membrane-binding domain.  
     
     
         70 . An isolated soluble polypeptide that comprises a fragment of the amino acid sequence of SEQ ID NO: 2 and has C3b/C4b complement receptor-like activity of the polypeptide set forth in SEQ ID NO: 2.  
     
     
         71 . The polypeptide of  claim 70 , wherein the soluble polypeptide lacks a transmembrane or a membrane-binding domain.  
     
     
         72 . A derivative of the polypeptide of  claim 70  or  71 .  
     
     
         73 . The derivative of  claim 72  which is covalently modified with a water-soluble polymer.  
     
     
         74 . The derivative of  claim 73  wherein the water-soluble polymer is selected from the group consisting of polyethylene glycol, monomethoxy-polyethylene glycol, dextran, cellulose, poly-(N-vinyl pyrrolidone) polyethylene glycol, propylene glycol homopolymers, polypropylene oxide/ethylene oxide co-polymers, polyoxyethylated polyols, and polyvinyl alcohol.  
     
     
         75 . A method for treating, preventing or ameliorating a medical condition comprising administering to a patient a polypeptide selected from the group consisting of: 
 (a) an isolated polypeptide encoded by a nucleic acid sequence selected from the group consisting of: 
 (i) a nucleotide sequence set forth in SEQ ID NO: 1;  
 (ii) a nucleotide sequence encoding the polypeptide as set forth in SEQ ID NO: 2;  
 (iii) a nucleotide sequence which hybridizes under stringent conditions to the complement of (a) or (b), wherein said stringent conditions comprise a final wash at 65° C. in 0.1×SSC and 0.1% SDS, wherein the nucleotide sequence encodes a polypeptide which has C3b/C4b complement receptor-like activity of the polypeptide set forth in SEQ ID NO: 2;  
   (b) an isolated polypeptide comprising the amino acid sequence set forth in SEQ ID NO: 2;    (c) an isolated polypeptide comprising the amino acid sequence of the mature C3b/C4b-like polypeptide wherein the mature polypeptide comprises the amino acid sequence as set forth in SEQ ID NO: 2, and optionally further comprises an amino-terminal methionine; and    (d) an isolated polypeptide comprising the amino acid sequence selected from the group consisting of: 
 (i) the amino acid sequence as set forth in SEQ ID NO: 2 with 1 to 100 conservative amino acid substitution(s), wherein the polypeptide has C3b/C4b complement receptor-like activity of the polypeptide set forth in SEQ ID NO: 2;  
 (ii) the amino acid sequence as set forth in SEQ ID NO: 2 with 1 to 100 amino acid insertion(s), wherein the polypeptide has C3b/C4b complement receptor-like activity of the polypeptide set forth in SEQ ID NO: 2;  
 (iii) the amino acid sequence as set forth in SEQ ID NO: 2 with 1 to 100 amino acid deletion(s), wherein the polypeptide has C3b/C4b complement receptor-like activity of the polypeptide set forth in SEQ ID NO: 2; and  
 (iv) the amino acid sequence as set forth in SEQ ID NO: 2 with a modification of 1 to 100 amino acids consisting of substitution(s), insertion(s), and deletion(s).  
   
     
     
         76 . A method for treating, preventing or ameliorating a medical condition comprising administering to a patient a polypeptide selected from the group consisting of: 
 (a) an isolated nucleic acid comprising a nucleotide sequence selected from the group consisting of: 
 (i) a nucleotide sequence set forth in SEQ ID NO: 1;  
 (ii) a nucleotide sequence encoding a polypeptide comprising an amino acid sequence as set forth in SEQ ID NO: 2;  
 (iii) a nucleotide sequence which hybridizes under stringent conditions to the complement of any of (b)-(d), wherein said stringent conditions comprise a final wash at 65° C. in 0.1×SSC and 0.1% SDS, wherein the nucleotide sequence encodes a polypeptide which has C3b/C4b complement receptor-like activity of the polypeptide set forth in SEQ ID NO: 2; and  
 (iv) a nucleotide sequence encoding a polypeptide comprising the amino acid sequence set forth in SEQ ID NO: 2 or encodes a fragment thereof comprising at least 25 amino acids of SEQ ID NO: 2 and having C3b/C4b complement receptor-like activity;  
   (b) a fragment of (a) wherein from 1 to 100 carboxy terminal codons have been deleted;    (c) a fragment of (a) or (b) wherein from 1 to 100 amino terminal codons have been deleted; and    (d) a nucleotide sequence fully complementary to any of (a)-(c).    
     
     
         77 . A method for treating, preventing or ameliorating a medical condition comprising administering to a patient an isolated polypeptide comprising the amino acid sequence set forth in SEQ ID NO: 2.  
     
     
         78 . A method for treating, preventing or ameliorating a medical condition comprising administering to a patient the antibody or fragment thereof of any one of claims  57 - 63 .  
     
     
         79 . A method for treating, preventing or ameliorating a medical condition comprising administering to a patient the nucleic acid molecule of  claim 68  or  69 .  
     
     
         80 . A method for treating, preventing or ameliorating a medical condition comprising administering to a patient the soluble polypeptide of  claim 70  or  71 .  
     
     
         81 . The method of any one of claims  75 - 80 , wherein the condition is characterized by insufficient, defective, or excessive C3b/C4b complement receptor-like activity.  
     
     
         82 . The method of any one of claims  75 - 80 , wherein the condition is characterized by insufficient, defective, or excessive complement activation.