US2021101992A1PendingUtilityA1
Cd83 binding proteins and uses thereof
Est. expiryOct 23, 2034(~8.2 yrs left)· nominal 20-yr term from priority
C07K 16/2803A61K 39/395C07K 2317/515C07K 2317/56C07K 2317/92A61P 3/10C07K 2317/55C07K 16/2896A61P 37/06A61P 31/18A61P 37/00A61P 35/00C07K 2317/21
40
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Claims
Abstract
The present invention provides an isolated or recombinant CD83 binding protein comprising an antigen binding domain, wherein the antigen binding domain binds specifically to CD83 or a cell expressing CD83.
Claims
exact text as granted — not AI-modified1 - 28 . (canceled)
29 . An isolated nucleic acid encoding a CD83 binding protein comprising an antigen binding domain that specifically binds to CD83, wherein the binding protein comprises:
three heavy chain complementarity determining regions (V H CDRs) comprising amino acid sequences as shown in SEQ ID NO:3 (V H CDR1), SEQ ID NO:4 (V H CDR2), and SEQ ID NO:5 (V H CDR3); and (i) three light chain complementarity determining regions (V L CDRs) comprising amino acid sequences as shown in SEQ ID NO:51 (V L CDR1), SEQ ID NO:52 (V L CDR2), and SEQ ID NO:53 (V L CDR3); or (ii) three light chain complementarity determining regions (V L CDRs) comprising amino acid sequences as shown in SEQ ID NO:54 (V L CDR1), SEQ ID NO:55 (V L CDR2), and SEQ ID NO:56 (V L CDR3); or (iii) three light chain complementarity determining regions (V L CDRs) comprising amino acid sequences as shown in SEQ ID NO:57 (V L CDR1), SEQ ID NO:58 (V L CDR2), and SEQ ID NO:59 (V L CDR3); or (iv) three light chain complementarity determining regions (V L CDRs) comprising amino acid sequences as shown in SEQ ID NO:60 (V L CDR1), SEQ ID NO:61 (V L CDR2), and SEQ ID NO:62 (V L CDR3); or (v) three light chain complementarity determining regions (V L CDRs) comprising amino acid sequences as shown in SEQ ID NO:63 (V L CDR1), SEQ ID NO:64 (V L CDR2), and SEQ ID NO:65 (V L CDR3); or (vi) three light chain complementarity determining regions (V L CDRs) comprising amino acid sequences as shown in SEQ ID NO:66 (V L CDR1), SEQ ID NO:67 (V L CDR2), and SEQ ID NO:68 (V L CDR3); or (vii) three light chain complementarity determining regions (V L CDRs) comprising amino acid sequences as shown in SEQ ID NO:69 (V L CDR1), SEQ ID NO:70 (V L CDR2), and SEQ ID NO:71 (V L CDR3); or (viii) three light chain complementarity determining regions (V L CDRs) comprising amino acid sequences as shown in SEQ ID NO:72 (V L CDR1), SEQ ID NO:73 (V L CDR2), and SEQ ID NO:74 (V L CDR3); or (ix) three light chain complementarity determining regions (V L CDRs) comprising amino acid sequences as shown in SEQ ID NO:75 (V L CDR1), SEQ ID NO:76 (V L CDR2), and SEQ ID NO:77 (V L CDR3); or (x) three light chain complementarity determining regions (V L CDRs) comprising amino acid sequences as shown in SEQ ID NO:78 (V L CDR1), SEQ ID NO:79 (V L CDR2), and SEQ ID NO:80 (V L CDR3); or (xi) three light chain complementarity determining regions (V L CDRs) comprising amino acid sequences as shown in SEQ ID NO:81 (V L CDR1), SEQ ID NO:82 (V L CDR2), and SEQ ID NO:83 (V L CDR3); or (xii) three light chain complementarity determining regions (V L CDRs) comprising amino acid sequences as shown in SEQ ID NO:84 (V L CDR1), SEQ ID NO:85 (V L CDR2), and SEQ ID NO:86 (V L CDR3).
30 . The isolated nucleic acid of claim 29 , wherein the binding protein comprises a heavy chain variable region (V H ) and a light chain variable region (V L ) in a single polypeptide chain.
31 . The isolated nucleic acid of claim 30 , wherein the binding protein is:
(i) a single chain Fv fragment (scFv); or (ii) a dimeric scFv (di-scFv); or (iii) (i) or (ii) linked to a Fc or a heavy chain constant domain (C H )2 and/or C H 3; or (iv) (i) or (ii) linked to a protein that binds to an immune effector cell.
32 . The isolated nucleic acid of claim 29 , wherein the binding protein comprises a heavy chain variable region (V H ) and a light chain variable region (V L ) in separate polypeptide chains.
33 . The isolated nucleic acid of claim 32 , wherein the binding protein is:
(i) a diabody; or (ii) a triabody; or (iii) a tetrabody; or (iv) a Fab; or (v) a F(ab′)2; or (vi) a Fv; or (vii) one of (i) to (vi) linked to a Fc or a C H 2 and/or C H 3; or (viii) one of (i) to (vi) linked to a protein that binds to an immune effector cell; or (ix) an antibody.
34 . The isolated nucleic acid of claim 33 , wherein the binding protein is an antibody.
35 . The isolated nucleic acid of claim 34 , wherein the antibody comprises:
(i) a V H sequence as shown in amino acids 1 to 115 of SEQ ID NO:2 and a V L sequence as shown in SEQ ID NO:6; or (ii) a V H sequence as shown in amino acids 1 to 115 of SEQ ID NO:2 and a V L sequence as shown in SEQ ID NO:7; or (iii) a V H sequence as shown in amino acids 1 to 115 of SEQ ID NO:2 and a V L sequence as shown in SEQ ID NO:8; or (iv) a V H sequence as shown in amino acids 1 to 115 of SEQ ID NO:2 and a V L sequence as shown in SEQ ID NO:9; or (v) a V H sequence as shown in amino acids 1 to 115 of SEQ ID NO:2 and a V L sequence as shown in SEQ ID NO:10; or (vi) a V H sequence as shown in amino acids 1 to 115 of SEQ ID NO:2 and a V L sequence as shown in SEQ ID NO:11; or (vii) a V H sequence as shown in amino acids 1 to 115 of SEQ ID NO:2 and a V L sequence as shown in SEQ ID NO:12; or (viii) a V H sequence as shown in amino acids 1 to 115 of SEQ ID NO:2 and a V L sequence as shown in SEQ ID NO:13; or (ix) a V H sequence as shown in amino acids 1 to 115 of SEQ ID NO:2 and a V L sequence as shown in SEQ ID NO:14; or (x) a V H sequence as shown in amino acids 1 to 115 of SEQ ID NO:2 and a V L sequence as shown in SEQ ID NO:15; or (xi) a V H sequence as shown in amino acids 1 to 115 of SEQ ID NO:2 and a V L sequence as shown in SEQ ID NO:16; or (xii) a V H sequence as shown in amino acids 1 to 115 of SEQ ID NO:2 and a V L sequence as shown in SEQ ID NO:17.
36 . The isolated nucleic acid of claim 35 , wherein the binding protein comprises a V H sequence as shown in amino acids 1 to 115 of SEQ ID NO:2 and a V L sequence as shown in SEQ ID NO:6.
37 . The isolated nucleic acid of claim 35 , wherein the binding protein comprises a heavy chain sequence as shown in SEQ ID NO:1 and a light chain sequence as shown in SEQ ID NO:31.
38 . The isolated nucleic acid of claim 29 , wherein the binding protein is a chimeric, de-immunized, humanized, synhumanized, human, primatized, or composite antibody.
39 . The isolated nucleic acid of claim 29 , wherein the binding protein comprises an Fc region capable of inducing an enhanced level of effector function compared to a human IgG1 or IgG4 Fc region and/or an Fc region capable of conferring an extended half-life compared to a human IgG1 or IgG4 Fc region.
40 . The isolated nucleic acid of claim 29 , wherein the binding protein competitively inhibits binding of an antibody to CD83 and/or binds to the same epitope on CD83 as an antibody, wherein the antibody comprises a heavy chain sequence as shown in SEQ ID NO:1 and a light chain sequence as shown in SEQ ID NO:31.
41 . The isolated nucleic acid of claim 29 , wherein the nucleic acid comprises or hybridizes under moderate to high stringency hybridization conditions to a nucleotide sequence as shown in SEQ ID NO: 30 or in any one of SEQ ID NOs: 32 to 43.
42 . An expression construct comprising the nucleic acid of claim 29 operably linked to a promoter.
43 . An isolated cell modified to express the nucleic acid of claim 29 .
44 . A composition comprising the isolated nucleic acid of claim 29 , and a suitable carrier.
45 . The composition of claim 44 , wherein the carrier is pharmaceutically acceptable.
46 . A method for treating or preventing a disease or condition caused by the dysfunction or undesired function of a cellular immune response involving T cells and/or dendritic cells in a subject, the method comprising administering a CD83 binding protein to the subject, wherein the CD83 binding protein comprises an antigen binding domain which specifically binds to CD83, wherein the binding protein comprises:
three heavy chain complementarity determining regions (V H CDRs) comprising amino acid sequences as shown in SEQ ID NO:3 (V H CDR1), SEQ ID NO:4 (V H CDR2), and SEQ ID NO:5 (V H CDR3); and (i) three light chain complementarity determining regions (V L CDRs) comprising amino acid sequences as shown in SEQ ID NO:51 (V L CDR1), SEQ ID NO:52 (V L CDR2), and SEQ ID NO:53 (V L CDR3); or (ii) three light chain complementarity determining regions (V L CDRs) comprising amino acid sequences as shown in SEQ ID NO:54 (V L CDR1), SEQ ID NO:55 (V L CDR2), and SEQ ID NO:56 (V L CDR3); or (iii) three light chain complementarity determining regions (V L CDRs) comprising amino acid sequences as shown in SEQ ID NO:57 (V L CDR1), SEQ ID NO:58 (V L CDR2), and SEQ ID NO:59 (V L CDR3); or (iv) three light chain complementarity determining regions (V L CDRs) comprising amino acid sequences as shown in SEQ ID NO:60 (V L CDR1), SEQ ID NO:61 (V L CDR2), and SEQ ID NO:62 (V L CDR3); or (v) three light chain complementarity determining regions (V L CDRs) comprising amino acid sequences as shown in SEQ ID NO:63 (V L CDR1), SEQ ID NO:64 (V L CDR2), and SEQ ID NO:65 (V L CDR3); or (vi) three light chain complementarity determining regions (V L CDRs) comprising amino acid sequences as shown in SEQ ID NO:66 (V L CDR1), SEQ ID NO:67 (V L CDR2), and SEQ ID NO:68 (V L CDR3); or (vii) three light chain complementarity determining regions (V L CDRs) comprising amino acid sequences as shown in SEQ ID NO:69 (V L CDR1), SEQ ID NO:70 (V L CDR2), and SEQ ID NO:71 (V L CDR3); or (viii) three light chain complementarity determining regions (V L CDRs) comprising amino acid sequences as shown in SEQ ID NO:72 (V L CDR1), SEQ ID NO:73 (V L CDR2), and SEQ ID NO:74 (V L CDR3); or (ix) three light chain complementarity determining regions (V L CDRs) comprising amino acid sequences as shown in SEQ ID NO:75 (V L CDR1), SEQ ID NO:76 (V L CDR2), and SEQ ID NO:77 (V L CDR3); or (x) three light chain complementarity determining regions (V L CDRs) comprising amino acid sequences as shown in SEQ ID NO:78 (V L CDR1), SEQ ID NO:79 (V L CDR2), and SEQ ID NO:80 (V L CDR3); or (xi) three light chain complementarity determining regions (V L CDRs) comprising amino acid sequences as shown in SEQ ID NO:81 (V L CDR1), SEQ ID NO:82 (V L CDR2), and SEQ ID NO:83 (V L CDR3); or (xii) three light chain complementarity determining regions (V L CDRs) comprising amino acid sequences as shown in SEQ ID NO:84 (V L CDR1), SEQ ID NO:85 (V L CDR2), and SEQ ID NO:86 (V L CDR3).
47 . A method for treating or preventing graft versus host disease, an allergy, asthma, rejection of a tissue or organ graft, an autoimmune condition, a skin disease, rheumatoid arthritis, insulin-dependent diabetes mellitus, a CD83 expressing neoplasia, or AIDS in a subject in need thereof, the method comprising administering a CD83 binding protein to the subject,
wherein the CD83 binding protein comprises an antigen binding domain which specifically binds to CD83, wherein the binding protein comprises:
three heavy chain complementarity determining regions (V H CDRs) comprising amino acid sequences as shown in SEQ ID NO:3 (V H CDR1), SEQ ID NO:4 (V H CDR2), and SEQ ID NO:5 (V H CDR3); and
(i) three light chain complementarity determining regions (V L CDRs) comprising amino acid sequences as shown in SEQ ID NO:51 (V L CDR1), SEQ ID NO:52 (V L CDR2), and SEQ ID NO:53 (V L CDR3); or
(ii) three light chain complementarity determining regions (V L CDRs) comprising amino acid sequences as shown in SEQ ID NO:54 (V L CDR1), SEQ ID NO:55 (V L CDR2), and SEQ ID NO:56 (V L CDR3); or
(iii) three light chain complementarity determining regions (V L CDRs) comprising amino acid sequences as shown in SEQ ID NO:57 (V L CDR1), SEQ ID NO:58 (V L CDR2), and SEQ ID NO:59 (V L CDR3); or
(iv) three light chain complementarity determining regions (V L CDRs) comprising amino acid sequences as shown in SEQ ID NO:60 (V L CDR1), SEQ ID NO:61 (V L CDR2), and SEQ ID NO:62 (V L CDR3); or
(v) three light chain complementarity determining regions (V L CDRs) comprising amino acid sequences as shown in SEQ ID NO:63 (V L CDR1), SEQ ID NO:64 (V L CDR2), and SEQ ID NO:65 (V L CDR3); or
(vi) three light chain complementarity determining regions (V L CDRs) comprising amino acid sequences as shown in SEQ ID NO:66 (V L CDR1), SEQ ID NO:67 (V L CDR2), and SEQ ID NO:68 (V L CDR3); or
(vii) three light chain complementarity determining regions (V L CDRs) comprising amino acid sequences as shown in SEQ ID NO:69 (V L CDR1), SEQ ID NO:70 (V L CDR2), and SEQ ID NO:71 (V L CDR3); or
(viii) three light chain complementarity determining regions (V L CDRs) comprising amino acid sequences as shown in SEQ ID NO:72 (V L CDR1), SEQ ID NO:73 (V L CDR2), and SEQ ID NO:74 (V L CDR3); or
(ix) three light chain complementarity determining regions (V L CDRs) comprising amino acid sequences as shown in SEQ ID NO:75 (V L CDR1), SEQ ID NO:76 (V L CDR2), and SEQ ID NO:77 (V L CDR3); or
(x) three light chain complementarity determining regions (V L CDRs) comprising amino acid sequences as shown in SEQ ID NO:78 (V L CDR1), SEQ ID NO:79 (V L CDR2), and SEQ ID NO:80 (V L CDR3); or
(xi) three light chain complementarity determining regions (V L CDRs) comprising amino acid sequences as shown in SEQ ID NO:81 (V L CDR1), SEQ ID NO:82 (V L CDR2), and SEQ ID NO:83 (V L CDR3); or
(xii) three light chain complementarity determining regions (V L CDRs) comprising amino acid sequences as shown in SEQ ID NO:84 (V L CDR1), SEQ ID NO:85 (V L CDR2), and SEQ ID NO:86 (V L CDR3),
wherein optionally the autoimmune condition is myasthenia gravis, multiple sclerosis, vasculitis, a chronic inflammatory bowel disease, an HLA B27-associated autoimmunopathy, or systemic lupus erythematosus; the skin disease is psoriasis; and/or the CD83-expressing neoplasia is a lymphoma or leukemia; and wherein further optionally the chronic inflammatory bowel disease is Crohn's disease or ulcerative colitis and/or the HLA B27-associated autoimmunopathy is Bechterew's disease.
48 . The method of claim 47 , wherein the method treats chronic or acute graft versus host disease.
49 . A method for downregulating the immunoactivity of an allogeneic graft or autologous graft, the method comprising contacting the graft with a CD83 binding protein,
wherein the CD83 binding protein comprises an antigen binding domain which specifically binds to CD83, wherein the binding protein comprises:
three heavy chain complementarity determining regions (V H CDRs) comprising amino acid sequences as shown in SEQ ID NO:3 (V H CDR1), SEQ ID NO:4 (V H CDR2), and SEQ ID NO:5 (V H CDR3); and
(i) three light chain complementarity determining regions (V L CDRs) comprising amino acid sequences as shown in SEQ ID NO:51 (V L CDR1), SEQ ID NO:52 (V L CDR2), and SEQ ID NO:53 (V L CDR3); or
(ii) three light chain complementarity determining regions (V L CDRs) comprising amino acid sequences as shown in SEQ ID NO:54 (V L CDR1), SEQ ID NO:55 (V L CDR2), and SEQ ID NO:56 (V L CDR3); or
(iii) three light chain complementarity determining regions (V L CDRs) comprising amino acid sequences as shown in SEQ ID NO:57 (V L CDR1), SEQ ID NO:58 (V L CDR2), and SEQ ID NO:59 (V L CDR3); or
(iv) three light chain complementarity determining regions (V L CDRs) comprising amino acid sequences as shown in SEQ ID NO:60 (V L CDR1), SEQ ID NO:61 (V L CDR2), and SEQ ID NO:62 (V L CDR3); or
(v) three light chain complementarity determining regions (V L CDRs) comprising amino acid sequences as shown in SEQ ID NO:63 (V L CDR1), SEQ ID NO:64 (V L CDR2), and SEQ ID NO:65 (V L CDR3); or
(vi) three light chain complementarity determining regions (V L CDRs) comprising amino acid sequences as shown in SEQ ID NO:66 (V L CDR1), SEQ ID NO:67 (V L CDR2), and SEQ ID NO:68 (V L CDR3); or
(vii) three light chain complementarity determining regions (V L CDRs) comprising amino acid sequences as shown in SEQ ID NO:69 (V L CDR1), SEQ ID NO:70 (V L CDR2), and SEQ ID NO:71 (V L CDR3); or
(viii) three light chain complementarity determining regions (V L CDRs) comprising amino acid sequences as shown in SEQ ID NO:72 (V L CDR1), SEQ ID NO:73 (V L CDR2), and SEQ ID NO:74 (V L CDR3); or
(ix) three light chain complementarity determining regions (V L CDRs) comprising amino acid sequences as shown in SEQ ID NO:75 (V L CDR1), SEQ ID NO:76 (V L CDR2), and SEQ ID NO:77 (V L CDR3); or
(x) three light chain complementarity determining regions (V L CDRs) comprising amino acid sequences as shown in SEQ ID NO:78 (V L CDR1), SEQ ID NO:79 (V L CDR2), and SEQ ID NO:80 (V L CDR3); or
(xi) three light chain complementarity determining regions (V L CDRs) comprising amino acid sequences as shown in SEQ ID NO:81 (V L CDR1), SEQ ID NO:82 (V L CDR2), and SEQ ID NO:83 (V L CDR3); or
(xii) three light chain complementarity determining regions (V L CDRs) comprising amino acid sequences as shown in SEQ ID NO:84 (V L CDR1), SEQ ID NO:85 (V L CDR2), and SEQ ID NO:86 (V L CDR3).Join the waitlist — get patent alerts
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