US2017073417A1PendingUtilityA1

Selective elimination of erosive cells

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Assignee: NOVO NORDISK ASPriority: Jun 17, 2011Filed: Nov 18, 2016Published: Mar 16, 2017
Est. expiryJun 17, 2031(~4.9 yrs left)· nominal 20-yr term from priority
Inventors:Kalle SoederstroemElisabeth Douglas Galsgaard
A61P 43/00A61P 19/10A61P 19/02C07K 16/2851C07K 2317/565C07K 2317/76C07K 2317/21C07K 2317/24A61K 39/395C07K 16/2803C07K 2317/73
49
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Claims

Abstract

The current invention relates to the treatment of diseases characterized by cartilage destruction and/or bone erosion. In particular the present invention relates to the treatment of osteoarthritis, osteoporosis, psoriatic arthritis or rheumatic arthritis with an anti-NKG2A antibody.

Claims

exact text as granted — not AI-modified
We claim: 
     
         1 . A method for treating cartilage destruction or bone erosion, comprising administering an anti-NKG2A antibody, or an antigen binding fragment thereof, to a subject in need thereof. 
     
     
         2 . The method of  claim 1 , wherein said anti-NKG2A antibody stimulates selective elimination of cartilage destructive cells or reduces formation of bone eroding cells. 
     
     
         3 . The method of  claim 2 , wherein the cartilage destructive cells are fibroblast-like synoviocytes (FLS). 
     
     
         4 . The method of  claim 2 , wherein the bone eroding cells are osteoclasts. 
     
     
         5 . The method of  claim 1 , wherein the anti-NKG2A antibody is a humanized or human antibody. 
     
     
         6 . The method of  claim 5 , wherein the anti-NKG2A antibody is humZ270 or humZ199. 
     
     
         7 . The method of  claim 1 , wherein the heavy chain of said anti-NKG2A antibody comprises:
 a CDR1 sequence of amino acid residues 31 to 35 (SYWMN) of SEQ ID NO: 2, wherein one or two of these amino acid residues may be substituted by a different amino acid residue; and/or   a CDR2 sequence of amino acids 50-59 (RIDPYDSETH) of SEQ ID NO: 2, wherein one, two or three of these amino acids residues may be substituted by a different amino acid residue; and/or   a CDR3 sequence of amino acids 95-102 (YCARGGYD) of SEQ ID NO: 2, wherein one, two or three of these amino acids residues may be substituted by a different amino acid;   
       and wherein the light chain of said anti-NKG2A antibody comprises:
 a CDR1 sequence of amino acid residues 24-34 (RASENIYSYLA) of SEQ ID NO: 3, wherein one, two or three of these amino acid residues may be substituted with a different amino acid; and/or 
 a CDR2 sequence of amino acid residues 50-56 (NAKTLAE) of SEQ ID NO: 3, wherein one or two of these amino acid residues may be substituted with a different amino acid; and/or 
 a CDR3 sequence of amino acid residues 89-97 (QHHYGTPRT) of SEQ ID NO: 3, wherein one, two or three of these amino acid residues may be substituted with a different amino acid. 
 
     
     
         8 . The method of  claim 1 , wherein the heavy chain of said anti-NKG2A antibody comprises:
 a CDR1 sequence of amino acid residues 31 to 35 (SYAMS) of SEQ ID NO: 4, wherein one or two of these amino acid residues may be substituted by a different amino acid residue; and/or   a CDR2 sequence of amino acids 50-65 (EISSGGSYTYYADSVK) of SEQ ID NO: 4, wherein one, two, three or four of these amino acids residues may be substituted by a different amino acid residue; and/or   a CDR3 sequence of amino acids 99-108 (HGDYPRFFDV) of SEQ ID NO: 4, wherein one, two or three of these amino acids residues may be substituted by a different amino acid;   
       and wherein the light chain of said anti-NKG2A antibody comprises:
 a CDR1 sequence of amino acid residues 24-34 (SASSSVSSYIY) of SEQ ID NO: 5, wherein one, two or three of these amino acid residues may be substituted with a different amino acid; and/or 
 a CDR2 sequence of amino acid residues 50-56 (LTSNLAS) of SEQ ID NO: 5, wherein one or two of these amino acid residues may be substituted with a different amino acid; and/or 
 a CDR3 sequence of amino acid residues 89-97 (QQWSGNPYT) of SEQ ID NO: 5, wherein one, two or three of these amino acid residues may be substituted with a different amino acid. 
 
     
     
         9 . The method of  claim 1 , wherein said anti-NKG2A antibody or an antigen binding fragment thereof, competes with an antibody comprising a heavy chain comprising:
 a CDR1 sequence of amino acid residues 31 to 35 (SYWMN) of SEQ ID NO: 2, wherein one or two of these amino acid residues may be substituted by a different amino acid residue; and/or   a CDR2 sequence of amino acids 50-59 (RIDPYDSETH) of SEQ ID NO: 2, wherein one, two or three of these amino acids residues may be substituted by a different amino acid residue; and/or   a CDR3 sequence of amino acids 95-102 (YCARGGYD) of SEQ ID NO: 2, wherein one, two or three of these amino acids residues may be substituted by a different amino acid;   
       and a light chain comprising:
 a CDR1 sequence of amino acid residues 24-34 (RASENIYSYLA) of SEQ ID NO: 3, wherein one, two or three of these amino acid residues may be substituted with a different amino acid; and/or 
 a CDR2 sequence of amino acid residues 50-56 (NAKTLAE) of SEQ ID NO: 3, wherein one or two of these amino acid residues may be substituted with a different amino acid; and/or 
 a CDR3 sequence of amino acid residues 89-97 (QHHYGTPRT) of SEQ ID NO: 3, wherein one, two or three of these amino acid residues may be substituted with a different amino acid. 
 
     
     
         10 . The method of  claim 1 , wherein said anti-NKG2A antibody or an antigen binding fragment thereof, competes with an antibody comprising a heavy chain comprising:
 a CDR1 sequence of amino acid residues 31 to 35 (SYAMS) of SEQ ID NO: 4, wherein one or two of these amino acid residues may be substituted by a different amino acid residue; and/or   a CDR2 sequence of amino acids 50-65 (EISSGGSYTYYADSVK) of SEQ ID NO: 4, wherein one, two, three or four of these amino acids residues may be substituted by a different amino acid residue; and/or   a CDR3 sequence of amino acids 99-108 (HGDYPRFFDV) of SEQ ID NO: 4, wherein one, two or three of these amino acids residues may be substituted by a different amino acid;   
       and a light chain comprising:
 a CDR1 sequence of amino acid residues 24-34 (SASSSVSSYIY) of SEQ ID NO: 5, wherein one, two or three of these amino acid residues may be substituted with a different amino acid; and/or 
 a CDR2 sequence of amino acid residues 50-56 (LTSNLAS) of SEQ ID NO: 5, wherein one or two of these amino acid residues may be substituted with a different amino acid; and/or 
 a CDR3 sequence of amino acid residues 89-97 (QQWSGNPYT) of SEQ ID NO: 5, wherein one, two or three of these amino acid residues may be substituted with a different amino acid. 
 
     
     
         11 . A method for treating a disease or disorder characterized by cartilage destruction or bone erosion, comprising administering an anti-NKG-2A antibody, or an antigen binding fragment thereof, to a subject in need thereof. 
     
     
         12 . The method of  claim 11 , wherein the disease or disorder is osteoarthritis. 
     
     
         13 . The method of  claim 11 , wherein the disease or disorder is osteoporosis. 
     
     
         14 . The method of  claim 11 , wherein the disease or disorder is psoriatic arthritis. 
     
     
         15 . The method of  claim 11 , wherein the disease or disorder is rheumatic arthritis. 
     
     
         16 . The method of  claim 11 , wherein the anti-NKG2A antibody is a humanized or human antibody. 
     
     
         17 . The method of  claim 16 , wherein the anti-NKG2A antibody is humZ270 or humZ199. 
     
     
         18 . The method of  claim 11 , wherein the heavy chain of said anti-NKG2A antibody comprises:
 a CDR1 sequence of amino acid residues 31 to 35 (SYWMN) of SEQ ID NO: 2, wherein one or two of these amino acid residues may be substituted by a different amino acid residue; and/or   a CDR2 sequence of amino acids 50-59 (RIDPYDSETH) of SEQ ID NO: 2, wherein one, two or three of these amino acids residues may be substituted by a different amino acid residue; and/or   a CDR3 sequence of amino acids 95-102 (YCARGGYD) of SEQ ID NO: 2, wherein one, two or three of these amino acids residues may be substituted by a different amino acid;   
       and wherein the light chain of said anti-NKG2A antibody comprises:
 a CDR1 sequence of amino acid residues 24-34 (RASENIYSYLA) of SEQ ID NO: 3, wherein one, two or three of these amino acid residues may be substituted with a different amino acid; and/or 
 a CDR2 sequence of amino acid residues 50-56 (NAKTLAE) of SEQ ID NO: 3, wherein one or two of these amino acid residues may be substituted with a different amino acid; and/or 
 a CDR3 sequence of amino acid residues 89-97 (QHHYGTPRT) of SEQ ID NO: 3, wherein one, two or three of these amino acid residues may be substituted with a different amino acid. 
 
     
     
         19 . The method of  claim 11 , wherein the heavy chain of said anti-NKG2A antibody comprises:
 a CDR1 sequence of amino acid residues 31 to 35 (SYAMS) of SEQ ID NO: 4, wherein one or two of these amino acid residues may be substituted by a different amino acid residue; and/or   a CDR2 sequence of amino acids 50-65 (EISSGGSYTYYADSVK) of SEQ ID NO: 4, wherein one, two, three or four of these amino acids residues may be substituted by a different amino acid residue; and/or   a CDR3 sequence of amino acids 99-108 (HGDYPRFFDV) of SEQ ID NO: 4, wherein one, two or three of these amino acids residues may be substituted by a different amino acid;   
       and wherein the light chain of said anti-NKG2A antibody comprises:
 a CDR1 sequence of amino acid residues 24-34 (SASSSVSSYIY) of SEQ ID NO: 5, wherein one, two or three of these amino acid residues may be substituted with a different amino acid; and/or 
 a CDR2 sequence of amino acid residues 50-56 (LTSNLAS) of SEQ ID NO: 5, wherein one or two of these amino acid residues may be substituted with a different amino acid; and/or 
 a CDR3 sequence of amino acid residues 89-97 (QQWSGNPYT) of SEQ ID NO: 5, wherein one, two or three of these amino acid residues may be substituted with a different amino acid. 
 
     
     
         20 . The method of  claim 11 , wherein said anti-NKG2A antibody or an antigen binding fragment thereof, competes with an antibody comprising a heavy chain comprising:
 a CDR1 sequence of amino acid residues 31 to 35 (SYWMN) of SEQ ID NO: 2, wherein one or two of these amino acid residues may be substituted by a different amino acid residue; and/or   a CDR2 sequence of amino acids 50-59 (RIDPYDSETH) of SEQ ID NO: 2, wherein one, two or three of these amino acids residues may be substituted by a different amino acid residue; and/or   a CDR3 sequence of amino acids 95-102 (YCARGGYD) of SEQ ID NO: 2, wherein one, two or three of these amino acids residues may be substituted by a different amino acid;   
       and a light chain comprising:
 a CDR1 sequence of amino acid residues 24-34 (RASENIYSYLA) of SEQ ID NO: 3, wherein one, two or three of these amino acid residues may be substituted with a different amino acid; and/or 
 a CDR2 sequence of amino acid residues 50-56 (NAKTLAE) of SEQ ID NO: 3, wherein one or two of these amino acid residues may be substituted with a different amino acid; and/or 
 a CDR3 sequence of amino acid residues 89-97 (QHHYGTPRT) of SEQ ID NO: 3, wherein one, two or three of these amino acid residues may be substituted with a different amino acid. 
 
     
     
         21 . The method of  claim 11 , wherein said anti-NKG2A antibody or an antigen binding fragment thereof, competes with an antibody comprising a heavy chain comprising:
 a CDR1 sequence of amino acid residues 31 to 35 (SYAMS) of SEQ ID NO: 4, wherein one or two of these amino acid residues may be substituted by a different amino acid residue; and/or   a CDR2 sequence of amino acids 50-65 (EISSGGSYTYYADSVK) of SEQ ID NO: 4, wherein one, two, three or four of these amino acids residues may be substituted by a different amino acid residue; and/or   a CDR3 sequence of amino acids 99-108 (HGDYPRFFDV) of SEQ ID NO: 4, wherein one, two or three of these amino acids residues may be substituted by a different amino acid;   
       and a light chain comprising:
 a CDR1 sequence of amino acid residues 24-34 (SASSSVSSYIY) of SEQ ID NO: 5, wherein one, two or three of these amino acid residues may be substituted with a different amino acid; and/or 
 a CDR2 sequence of amino acid residues 50-56 (LTSNLAS) of SEQ ID NO: 5, wherein one or two of these amino acid residues may be substituted with a different amino acid; and/or 
 a CDR3 sequence of amino acid residues 89-97 (QQWSGNPYT) of SEQ ID NO: 5, wherein one, two or three of these amino acid residues may be substituted with a different amino acid.

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