US2008267967A1PendingUtilityA1

Modulation of cd200 receptors

49
Assignee: GORCZYNSKI REGINALD MPriority: May 24, 2001Filed: Mar 27, 2008Published: Oct 30, 2008
Est. expiryMay 24, 2021(expired)· nominal 20-yr term from priority
Inventors:Reginald M. GorczynskiPhilip Marsden
G01N 33/505C07K 2319/30C07K 16/2803G01N 2500/04A61P 37/00A61K 2039/505G01N 33/5047G01N 33/5044A61K 2035/122G01N 33/5008C07K 14/70596A61K 38/00G01N 33/502C07K 2317/54G01N 33/566C07K 14/70503A61K 48/00G01N 2500/20C07K 2317/34C07K 2319/00A61K 40/50A61K 40/421A61K 40/418A61K 40/24A61K 40/22A61K 40/19
49
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Claims

Abstract

The present invention relates to CD200 receptor isoforms and modulators thereof and their use in methods of immune modulation and pharmaceutical compositions.

Claims

exact text as granted — not AI-modified
1 . An isolated CD200R2a nucleic acid molecule encoding a protein having the amino acid sequence shown in  FIG. 4  (SEQ ID NO:2) or a homolog or analog thereof. 
     
     
         2 . An isolated CD200a nucleic acid molecule wherein the nucleic acid sequence comprises:
 (a) a nucleic acid sequence as shown in  FIG. 1  (SEQ ID NO:1), wherein T can also be U;   (b) a nucleic acid sequence that is complimentary to a nucleic acid sequence of (a);   (c) a nucleic acid sequence that has substantial sequence homology to a nucleic acid sequence of (a) or (b);   (d) a nucleic acid sequence that is an analog of a nucleic acid sequence of (a), (b) or (c); or   (e) a nucleic acid sequence that hybridizes to a nucleic acid sequence of (a), (b), (c) or (d) under stringent hybridization conditions.   
     
     
         3 . An isolated CD200R2b nucleic acid molecule encoding a protein having the amino acid sequence shown in  FIG. 5  (SEQ ID NO:4) or a homolog or analog thereof. 
     
     
         4 . An isolated CD200R2b nucleic acid molecule wherein the nucleic acid sequence comprises:
 (a) a nucleic acid sequence as shown in  FIG. 2  (SEQ ID NO:3), wherein T can also be U;   (b) a nucleic acid sequence that is complimentary to a nucleic acid sequence of (a);   (c) a nucleic acid sequence that has substantial sequence homology to a nucleic acid sequence of (a) or (b);   (d) a nucleic acid sequence that is an analog of a nucleic acid sequence of (a), (b) or (c); or   (e) a nucleic acid sequence that hybridizes to a nucleic acid sequence of (a), (b), (c) or (d) under stringent hybridization conditions.   
     
     
         5 . An isolated CD200R3a nucleic acid molecule encoding a protein having the amino acid sequence shown in  FIG. 6  (SEQ ID NO:6) or a homolog or analog thereof. 
     
     
         6 . An isolated CD200R3a nucleic acid molecule wherein the nucleic acid sequence comprises:
 (a) a nucleic acid sequence as shown in  FIG. 3  (SEQ ID NO:5), wherein T can also be U;   (b) a nucleic acid sequence that is complimentary to a nucleic acid sequence of (a);   (c) a nucleic acid sequence that has substantial sequence homology to a nucleic acid sequence of (a) or (b);   (d) a nucleic acid sequence that is an analog of a nucleic acid sequence of (a), (b) or (c); or   (e) a nucleic acid sequence that hybridizes to a nucleic acid sequence of (a), (b), (c) or (d) under stringent hybridization conditions.   
     
     
         7 . An isolated CD200R2a protein having an amino acid sequence shown in  FIG. 4  (SEQ ID NO:2) or an analog, homolog or fragment thereof. 
     
     
         8 . An isolated CD200R2b protein having an amino acid sequence shown in  FIG. 5  (SEQ ID NO:4) or an analog, homolog or fragment thereof. 
     
     
         9 . An isolated CD200R3a protein having an amino acid sequence shown in  FIG. 6  (SEQ ID NO:6) or an analog, homolog or fragment thereof. 
     
     
         10 . An antibody that binds to an isolated protein according to any one of  claims 7 - 10 . 
     
     
         11 . An antibody according to  claim 10  which is a monoclonal antibody. 
     
     
         12 . A use of an effective amount of a nucleic acid sequence according to any one of  claims 1 - 6 , a protein according to any one of  claims 7 - 10  or an antibody according to  claim 10  or  11  for the manufacture of a medicament to modulate an immune response. 
     
     
         13 . A use according to  claim 12  comprising modulating an immune response involved in graft rejection, fetal loss, autoimmunity, allergy, inflammatory conditions, skin conditions or cancer. 
     
     
         14 . A pharmaceutical composition for use in modulating an immune response comprising an effective amount of a nucleic acid according to any one of  claims 1 - 6 , a protein according to  claims 7 - 10 , or an antibody according to  claim 10  or  11  in admixture with a suitable diluent or carrier. 
     
     
         15 . A use of an effective amount of a CD200 receptor agonist for the manufacture of a medicament to suppress an immune response. 
     
     
         16 . A use according to  claim 15  wherein said agonist is an antibody, small molecule, peptide mimetic or peptide. 
     
     
         17 . A use according to  claim 15  wherein the agonist is an antibody that crosslinks a CD200 receptor. 
     
     
         18 . A use according to  claim 17  wherein the antibody is a whole immunoglobulin that binds to a CD200 receptor. 
     
     
         19 . A use according to  claim 17  or  18  wherein said antibody binds to a CD200R3a receptor. 
     
     
         20 . A use according to  claim 19  wherein the antibody binds to a CD200R3a receptor which has the sequence shown in  FIG. 6  (SEQ ID NO:6) or a homolog or analog thereof. 
     
     
         21 . A use according to any one of  claims 15 - 20  for preventing or treating transplant rejection, fetal loss, allergy, inflammatory conditions or skin conditions. 
     
     
         22 . A use according to any one of  claims 15 - 20  for preventing or treating an autoimmune disease. 
     
     
         23 . A use according to  claim 22  for preventing or treating arthritis. 
     
     
         24 . A use according to  claim 22  for preventing or treating diabetes. 
     
     
         25 . A use according to any one of  claims 15  to  24  wherein said agonist is administered with an additional immune suppressant. 
     
     
         26 . A use according to  claim 25  wherein said immune suppressant is selected from CD200 or fragment thereof, immune suppressive cytokines and/or anti-inflammatory agents. 
     
     
         27 . A use of an effective amount of CD200 receptor antagonist for the manufacture of a medicament to inhibit immune suppression. 
     
     
         28 . A use according to  claim 27  wherein said antagonist is an antibody, antibody fragment, small molecule, peptide mimetic, peptide or an antisense oligonucleotide. 
     
     
         29 . A use according to  claim 27  wherein the antagonist is an antibody that binds to the CD200 receptor but does not cause activation thereof. 
     
     
         30 . A use according to  claim 29  wherein the antibody is an F(ab′) 2  or Fab fragment. 
     
     
         31 . A use according to  claim 30  wherein said antibody binds to a CD200R3a receptor. 
     
     
         32 . A use according to  claim 31  wherein the antibody binds to a CD200R3a receptor which has the sequence shown in  FIG. 6  (SEQ ID NO:6) or a homolog or analog thereof. 
     
     
         33 . A use according to any one of  claims 27  to  32  for the treatment or prevention of viral, bacterial or fungal infections or cancer. 
     
     
         34 . A use according to any one of  claims 27  to  33  wherein said antagonist is administered with an immune stimulant. 
     
     
         35 . A use according to  claim 34  wherein said immune stimulant is a cytokine. 
     
     
         36 . A method of preparing suppressive antigen presenting cells comprising culturing a starting cell population in the presence of an effective amount of CD200 receptor agonist. 
     
     
         37 . A method according to  claim 36  wherein the agonist is an antibody that crosslinks a CD200 receptor. 
     
     
         38 . A method according to  claim 36  or  37  wherein the antigen presenting cell is a dendritic cell. 
     
     
         39 . A method according to any one of  claims 36  to  38  wherein the starting cell population contains bone marrow cells. 
     
     
         40 . A use of an effective amount of a population of suppressive antigen presenting cells prepared according to the method of any one of  claims 36  to  39  in the manufacture of a medicament to suppress an immune response. 
     
     
         41 . A method of preparing suppressive T cells comprising culturing to a cell population containing T cells or precursors thereof in the presence of suppressive antigen presenting cells prepared according to the method of any one of  claims 36  to  39 . 
     
     
         42 . A use of an effective amount of a population of suppressive T cells prepared according to the method of  claim 41  for the manufacture of a medicament to suppress an immune response. 
     
     
         43 . A method of identifying substances which bind with a CD200 receptor, comprising the steps of:
 (a) reacting the CD200 receptor and a test substance, under conditions which allow for formation of a complex, and   (b) assaying for complexes of the CD200 receptor and the test substance, for free substance, and for non-complexed CD200 receptor, wherein the presence of complexes indicates that the test substance is capable of binding the CD200 receptor.   
     
     
         44 . A method according to  claim 43  wherein the CD200 receptor is according to any one of  claims 1  to  9 . 
     
     
         45 . A method for identifying a compound that modulates a CD200 receptor comprising:
 (a) incubating a test compound with a CD200 receptor protein or a nucleic acid encoding a CD200 receptor protein; and   (b) determining an amount of CD200 receptor protein activity or expression and comparing with a control, wherein a change in the CD200 receptor protein activity or expression as compared to the control indicates that the test compound modulates a CD200 receptor.   
     
     
         46 . A method of identifying a CD200 receptor agonist comprising the steps of:
 (a) incubating a test substance with a CD200 receptor; and   (b) determining whether or not the test substance stimulates the CD200 receptor.   
     
     
         47 . A method of identifying a CD200 receptor antagonist comprising the steps of:
 (a) incubating a test substance with a CD200 receptor; and   (b) determining whether or not the test substance inhibits the CD200 receptor.   
     
     
         48 . A method according to any one of  claim 45  to  47  wherein the CD200 receptor is according to any one of  claims 1  to  9 . 
     
     
         49 . A method according to any one of  claims 45  to  48  wherein the CD200 receptor is expressed on the surface of a cell. 
     
     
         50 . A CD200 receptor modulator identified according to the method of any one of  claims 45  to  49 . 
     
     
         51 . A method of preparing a pharmaceutical composition for use in modulating an immune response comprising mixing a modulator of a CD200 receptor identified according to the method of any one of  claims 45  to  49  with a suitable diluent or carrier.

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