ANTIBODIES AGAINST MONOCYTE CHEMOTACTIC PROTEINS

التفاصيل البيبلوغرافية
العنوان: ANTIBODIES AGAINST MONOCYTE CHEMOTACTIC PROTEINS
Document Number: 20100166757
تاريخ النشر: July 1, 2010
Appl. No: 12/612087
Application Filed: November 04, 2009
مستخلص: The invention provides antibodies that bind to a plurality of β-chemokines, particularly monocyte chemotactic proteins MCP-1, MCP-2 and MCP-3. The invention also provides cells producing the antibodies, and methods of making and using the same.
Inventors: De Fougerolles, Antonin R. (Brookline, MA, US); Kotelianski, Victor E. (Boston, MA, US); Reid, Carl (Mattapan, MA, US); Garber, Ellen (Cambridge, MA, US)
Claim: 1-55. (canceled)
Claim: 56. A method of treating a subject suffering from a disorder selected from the group consisting of glomerulonephritis, scleroderma, cirrhosis, multiple sclerosis, lupus nephritis, atherosclerosis, inflammatory bowel disease or rheumatoid arthritis, comprising administering to the subject an isolated antibody or fragment thereof, wherein said antibody or fragment thereof binds a plurality of β-chemokines, wherein said plurality of β-chemokines comprise MCP-1 and at least one other β-chemokine, wherein said antibody or antigen-binding fragment comprises: a) a heavy chain variable region having a CDR1 domain comprising the sequence set forth in SEQ ID NO:29, a CDR2 domain comprising the sequence set forth in SEQ ID NO:30, and a CDR3 domain comprising the sequence set forth in SEQ ID NO: 31; and b) a light chain variable region having a CDR1 domain comprising the sequence set forth in SEQ ID NO:32, a CDR2 domain comprising the sequence set forth in SEQ ID NO:33, and a CDR3 domain comprising the sequence set forth in SEQ ID NO:34.
Claim: 57-75. (canceled)
Claim: 76. The method of claim 56, wherein the at least one other β-chemokine is MCP-2.
Claim: 77. The method of claim 56, wherein the antibody is a chimeric antibody.
Claim: 78. The method of claim 56, wherein the antibody is a humanized antibody.
Claim: 79. The method of claim 56, wherein the fragment is an Fab fragment.
Claim: 80. The method of claim 56, wherein the antibody is modified by reducing or eliminating at least one potential glycosylation site.
Claim: 81. The method of claim 56, wherein the antibody is modified by conjugation to a carrier selected from polyethylene glycol and albumen.
Claim: 82. The method of claim 56, wherein the constant region of the antibody is modified to reduce at least one constant region-mediated biological effector function relative to an unmodified antibody selected from the group of binding to an Fc receptor, opsonization, phagocytosis, and antigen-dependent cellular cytotoxicity.
Claim: 83. A method of treating a subject suffering from a disorder selected from the group consisting of glomerulonephritis, scleroderma, cirrhosis, multiple sclerosis, lupus nephritis, atherosclerosis, inflammatory bowel disease or rheumatoid arthritis, comprising administering to the subject an isolated antibody heavy chain, wherein said antibody heavy chain comprises a variable region complementarity determining region (CDR) from an antibody heavy chain variable region set forth in SEQ ID NO:27.
Claim: 84. A method of treating a subject suffering from a disorder selected from the group consisting of glomerulonephritis, scleroderma, cirrhosis, multiple sclerosis, lupus nephritis, atherosclerosis, inflammatory bowel disease or rheumatoid arthritis, comprising administering to the subject an isolated antibody light chain, wherein said antibody light chain comprises a variable region complementarity determining region (CDR) from an antibody light chain variable region as set forth in SEQ ID NO:28.
Claim: 85. A method of treating a subject suffering from a disorder selected from the group consisting of glomerulonephritis, scleroderma, cirrhosis, multiple sclerosis, lupus nephritis, atherosclerosis, inflammatory bowel disease or rheumatoid arthritis, comprising administering to the subject an isolated antibody or antigen-binding fragment thereof, wherein said antibody or antigen-binding fragment thereof comprises a variable heavy chain region as set forth in SEQ ID NO:27 and a variable light chain region as set forth in SEQ ID NO:28
Claim: 86. A method of treating a subject suffering from a disorder selected from the group consisting of glomerulonephritis, scleroderma, cirrhosis, multiple sclerosis, lupus nephritis, atherosclerosis, inflammatory bowel disease or rheumatoid arthritis, comprising administering to the subject an isolated antibody or antigen-binding fragment thereof, wherein said antibody or antigen-binding fragment binds a plurality of β-chemokines, wherein said plurality of β-chemokines comprises MCP-1 and at least one other β-chemokine, wherein said antibody or antigen-binding fragment thereof comprises a variable region complementarity determining region (CDR) from a heavy chain variable region set forth in SEQ ID NO:27.
Claim: 87. The method of claim 86, wherein the at least one other β-chemokine includes MCP-2.
Claim: 88. A method of treating a subject suffering from a disorder selected from the group consisting of glomerulonephritis, scleroderma, cirrhosis, multiple sclerosis, lupus nephritis, atherosclerosis, inflammatory bowel disease or rheumatoid arthritis, comprising administering to the subject an antibody or antigen-binding fragment thereof, wherein said antibody or antigen-binding fragment binds a plurality of β-chemokines, wherein said plurality of β-chemokines comprises MCP-1 and at least one other β-chemokine, wherein said antibody or antigen-binding fragment thereof comprises a variable region complementarity determining region (CDR) from a light chain variable region set forth in SEQ ID NO:28.
Claim: 89. The method of claim 88, wherein the at least one other β-chemokine includes MCP-2.
Claim: 90. A method of treating a subject suffering from a disorder selected from the group consisting of glomerulonephritis, scleroderma, cirrhosis, multiple sclerosis, lupus nephritis, atherosclerosis, inflammatory bowel disease or rheumatoid arthritis, comprising administering to the subject an isolated single-chain antibody antigen-binding fragment, wherein said single-chain antibody antigen-binding fragment specifically binds MCP-1 and at least one other monocyte chemotactic protein, wherein said single-chain antibody antigen-binding fragment comprises a heavy chain variable region complementarity determining region (CDR) from an antibody heavy chain variable region set forth in SEQ ID NO:27 or a light chain variable region complementarity determining region (CDR) from an antibody light chain variable region set forth in SEQ ID NO:28, wherein said antibody fragment does not have agonistic activity for MCP-2.
Claim: 91. The method of claim 90, wherein the antibody antigen-binding fragment comprises a variable heavy chain region as set forth in SEQ ID NO: 27 and a variable light chain region as set forth in SEQ ID NO:28.
Claim: 92. The method of claim 90, wherein the antibody antigen-binding fragment binds a plurality of β-chemokines, wherein said plurality of β-chemokines comprises MCP-1 and at least one other β-chemokine, wherein said antibody antigen-binding fragment comprises: i. a heavy chain variable region having a CDR1 domain comprising the sequence set forth in SEQ ID NO:29, a CDR2 domain comprising the sequence set forth in SEQ ID NO:30, and a CDR3 domain comprising the sequence set forth in SEQ ID NO:31; and ii. a light chain variable region having a CDR1 domain comprising the sequence set forth in SEQ ID NO:32 a CDR2 domain comprising the sequence set forth in SEQ ID NO:33, and a CDR3 domain comprising the sequence set forth in SEQ ID NO:34.
Claim: 93. The method of claim 90, wherein the antibody antigen-binding fragment specifically binds to MCP-1, MCP-2, and MCP-3.
Claim: 94. The method of claim 90, wherein the antibody antigen-binding fragment is a monoclonal or antigen-binding fragment.
Claim: 95. The method of claim 90, wherein the antibody antigen-binding fragment is a humanized antibody.
Claim: 96. The method of claim 90, wherein the antibody antigen-binding fragment is selected from the group consisting of an Fab fragment, an Fab′ fragment, an F(ab)2 fragment, and an Fv fragment.
Claim: 97. The method of claim 90, wherein the antibody antigen-binding fragment is an Fab fragment.
Claim: 98. The method of claim 90, wherein the antibody antigen-binding fragment is conjugated to polyethylene glycol or albumen.
Claim: 99. The method of claim 90, wherein the antibody antigen-binding fragment has a Kd for binding affinity to MCP-1 of 1 pM or less or 0.4 pM to about 0.7 pM.
Current U.S. Class: 4241/351
Current International Class: 61; 61; 61; 61; 61; 61; 61; 61; 61
رقم الانضمام: edspap.20100166757
قاعدة البيانات: USPTO Patent Applications
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Array ( [Name] => DateEntry [Label] => Publication Date [Group] => Patent [Data] => July 1, 2010 )
Array ( [Name] => DocumentID [Label] => Appl. No [Group] => Patent [Data] => 12/612087 )
Array ( [Name] => DateFiled [Label] => Application Filed [Group] => Patent [Data] => November 04, 2009 )
Array ( [Name] => Abstract [Label] => Abstract [Group] => Ab [Data] => The invention provides antibodies that bind to a plurality of β-chemokines, particularly monocyte chemotactic proteins MCP-1, MCP-2 and MCP-3. The invention also provides cells producing the antibodies, and methods of making and using the same. )
Array ( [Name] => Author [Label] => Inventors [Group] => Patent [Data] => <searchLink fieldCode="ZA" term="%22De+Fougerolles%2C+Antonin+R%2E%22">De Fougerolles, Antonin R.</searchLink> (Brookline, MA, US); <searchLink fieldCode="ZA" term="%22Kotelianski%2C+Victor+E%2E%22">Kotelianski, Victor E.</searchLink> (Boston, MA, US); <searchLink fieldCode="ZA" term="%22Reid%2C+Carl%22">Reid, Carl</searchLink> (Mattapan, MA, US); <searchLink fieldCode="ZA" term="%22Garber%2C+Ellen%22">Garber, Ellen</searchLink> (Cambridge, MA, US) )
Array ( [Name] => Comment [Label] => Claim [Group] => Patent [Data] => 1-55. (canceled) )
Array ( [Name] => Comment [Label] => Claim [Group] => Patent [Data] => 56. A method of treating a subject suffering from a disorder selected from the group consisting of glomerulonephritis, scleroderma, cirrhosis, multiple sclerosis, lupus nephritis, atherosclerosis, inflammatory bowel disease or rheumatoid arthritis, comprising administering to the subject an isolated antibody or fragment thereof, wherein said antibody or fragment thereof binds a plurality of β-chemokines, wherein said plurality of β-chemokines comprise MCP-1 and at least one other β-chemokine, wherein said antibody or antigen-binding fragment comprises: a) a heavy chain variable region having a CDR1 domain comprising the sequence set forth in SEQ ID NO:29, a CDR2 domain comprising the sequence set forth in SEQ ID NO:30, and a CDR3 domain comprising the sequence set forth in SEQ ID NO: 31; and b) a light chain variable region having a CDR1 domain comprising the sequence set forth in SEQ ID NO:32, a CDR2 domain comprising the sequence set forth in SEQ ID NO:33, and a CDR3 domain comprising the sequence set forth in SEQ ID NO:34. )
Array ( [Name] => Comment [Label] => Claim [Group] => Patent [Data] => 57-75. (canceled) )
Array ( [Name] => Comment [Label] => Claim [Group] => Patent [Data] => 76. The method of claim 56, wherein the at least one other β-chemokine is MCP-2. )
Array ( [Name] => Comment [Label] => Claim [Group] => Patent [Data] => 77. The method of claim 56, wherein the antibody is a chimeric antibody. )
Array ( [Name] => Comment [Label] => Claim [Group] => Patent [Data] => 78. The method of claim 56, wherein the antibody is a humanized antibody. )
Array ( [Name] => Comment [Label] => Claim [Group] => Patent [Data] => 79. The method of claim 56, wherein the fragment is an Fab fragment. )
Array ( [Name] => Comment [Label] => Claim [Group] => Patent [Data] => 80. The method of claim 56, wherein the antibody is modified by reducing or eliminating at least one potential glycosylation site. )
Array ( [Name] => Comment [Label] => Claim [Group] => Patent [Data] => 81. The method of claim 56, wherein the antibody is modified by conjugation to a carrier selected from polyethylene glycol and albumen. )
Array ( [Name] => Comment [Label] => Claim [Group] => Patent [Data] => 82. The method of claim 56, wherein the constant region of the antibody is modified to reduce at least one constant region-mediated biological effector function relative to an unmodified antibody selected from the group of binding to an Fc receptor, opsonization, phagocytosis, and antigen-dependent cellular cytotoxicity. )
Array ( [Name] => Comment [Label] => Claim [Group] => Patent [Data] => 83. A method of treating a subject suffering from a disorder selected from the group consisting of glomerulonephritis, scleroderma, cirrhosis, multiple sclerosis, lupus nephritis, atherosclerosis, inflammatory bowel disease or rheumatoid arthritis, comprising administering to the subject an isolated antibody heavy chain, wherein said antibody heavy chain comprises a variable region complementarity determining region (CDR) from an antibody heavy chain variable region set forth in SEQ ID NO:27. )
Array ( [Name] => Comment [Label] => Claim [Group] => Patent [Data] => 84. A method of treating a subject suffering from a disorder selected from the group consisting of glomerulonephritis, scleroderma, cirrhosis, multiple sclerosis, lupus nephritis, atherosclerosis, inflammatory bowel disease or rheumatoid arthritis, comprising administering to the subject an isolated antibody light chain, wherein said antibody light chain comprises a variable region complementarity determining region (CDR) from an antibody light chain variable region as set forth in SEQ ID NO:28. )
Array ( [Name] => Comment [Label] => Claim [Group] => Patent [Data] => 85. A method of treating a subject suffering from a disorder selected from the group consisting of glomerulonephritis, scleroderma, cirrhosis, multiple sclerosis, lupus nephritis, atherosclerosis, inflammatory bowel disease or rheumatoid arthritis, comprising administering to the subject an isolated antibody or antigen-binding fragment thereof, wherein said antibody or antigen-binding fragment thereof comprises a variable heavy chain region as set forth in SEQ ID NO:27 and a variable light chain region as set forth in SEQ ID NO:28 )
Array ( [Name] => Comment [Label] => Claim [Group] => Patent [Data] => 86. A method of treating a subject suffering from a disorder selected from the group consisting of glomerulonephritis, scleroderma, cirrhosis, multiple sclerosis, lupus nephritis, atherosclerosis, inflammatory bowel disease or rheumatoid arthritis, comprising administering to the subject an isolated antibody or antigen-binding fragment thereof, wherein said antibody or antigen-binding fragment binds a plurality of β-chemokines, wherein said plurality of β-chemokines comprises MCP-1 and at least one other β-chemokine, wherein said antibody or antigen-binding fragment thereof comprises a variable region complementarity determining region (CDR) from a heavy chain variable region set forth in SEQ ID NO:27. )
Array ( [Name] => Comment [Label] => Claim [Group] => Patent [Data] => 87. The method of claim 86, wherein the at least one other β-chemokine includes MCP-2. )
Array ( [Name] => Comment [Label] => Claim [Group] => Patent [Data] => 88. A method of treating a subject suffering from a disorder selected from the group consisting of glomerulonephritis, scleroderma, cirrhosis, multiple sclerosis, lupus nephritis, atherosclerosis, inflammatory bowel disease or rheumatoid arthritis, comprising administering to the subject an antibody or antigen-binding fragment thereof, wherein said antibody or antigen-binding fragment binds a plurality of β-chemokines, wherein said plurality of β-chemokines comprises MCP-1 and at least one other β-chemokine, wherein said antibody or antigen-binding fragment thereof comprises a variable region complementarity determining region (CDR) from a light chain variable region set forth in SEQ ID NO:28. )
Array ( [Name] => Comment [Label] => Claim [Group] => Patent [Data] => 89. The method of claim 88, wherein the at least one other β-chemokine includes MCP-2. )
Array ( [Name] => Comment [Label] => Claim [Group] => Patent [Data] => 90. A method of treating a subject suffering from a disorder selected from the group consisting of glomerulonephritis, scleroderma, cirrhosis, multiple sclerosis, lupus nephritis, atherosclerosis, inflammatory bowel disease or rheumatoid arthritis, comprising administering to the subject an isolated single-chain antibody antigen-binding fragment, wherein said single-chain antibody antigen-binding fragment specifically binds MCP-1 and at least one other monocyte chemotactic protein, wherein said single-chain antibody antigen-binding fragment comprises a heavy chain variable region complementarity determining region (CDR) from an antibody heavy chain variable region set forth in SEQ ID NO:27 or a light chain variable region complementarity determining region (CDR) from an antibody light chain variable region set forth in SEQ ID NO:28, wherein said antibody fragment does not have agonistic activity for MCP-2. )
Array ( [Name] => Comment [Label] => Claim [Group] => Patent [Data] => 91. The method of claim 90, wherein the antibody antigen-binding fragment comprises a variable heavy chain region as set forth in SEQ ID NO: 27 and a variable light chain region as set forth in SEQ ID NO:28. )
Array ( [Name] => Comment [Label] => Claim [Group] => Patent [Data] => 92. The method of claim 90, wherein the antibody antigen-binding fragment binds a plurality of β-chemokines, wherein said plurality of β-chemokines comprises MCP-1 and at least one other β-chemokine, wherein said antibody antigen-binding fragment comprises: i. a heavy chain variable region having a CDR1 domain comprising the sequence set forth in SEQ ID NO:29, a CDR2 domain comprising the sequence set forth in SEQ ID NO:30, and a CDR3 domain comprising the sequence set forth in SEQ ID NO:31; and ii. a light chain variable region having a CDR1 domain comprising the sequence set forth in SEQ ID NO:32 a CDR2 domain comprising the sequence set forth in SEQ ID NO:33, and a CDR3 domain comprising the sequence set forth in SEQ ID NO:34. )
Array ( [Name] => Comment [Label] => Claim [Group] => Patent [Data] => 93. The method of claim 90, wherein the antibody antigen-binding fragment specifically binds to MCP-1, MCP-2, and MCP-3. )
Array ( [Name] => Comment [Label] => Claim [Group] => Patent [Data] => 94. The method of claim 90, wherein the antibody antigen-binding fragment is a monoclonal or antigen-binding fragment. )
Array ( [Name] => Comment [Label] => Claim [Group] => Patent [Data] => 95. The method of claim 90, wherein the antibody antigen-binding fragment is a humanized antibody. )
Array ( [Name] => Comment [Label] => Claim [Group] => Patent [Data] => 96. The method of claim 90, wherein the antibody antigen-binding fragment is selected from the group consisting of an Fab fragment, an Fab′ fragment, an F(ab)2 fragment, and an Fv fragment. )
Array ( [Name] => Comment [Label] => Claim [Group] => Patent [Data] => 97. The method of claim 90, wherein the antibody antigen-binding fragment is an Fab fragment. )
Array ( [Name] => Comment [Label] => Claim [Group] => Patent [Data] => 98. The method of claim 90, wherein the antibody antigen-binding fragment is conjugated to polyethylene glycol or albumen. )
Array ( [Name] => Comment [Label] => Claim [Group] => Patent [Data] => 99. The method of claim 90, wherein the antibody antigen-binding fragment has a Kd for binding affinity to MCP-1 of 1 pM or less or 0.4 pM to about 0.7 pM. )
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