Patent application EP19183345A (EP), filed 2019-06-28
Publication number: EP3757127A1
Title: DEIMMUNIZED ANTIBODIES BINDING TO ALPHA-4 INTEGRIN AND USES THEREOF
Abstract: The present invention provides deimmunized antibodies binding to α4 integrin. In particular, modified versions of natalizumab are provided, in which the immunogenicity is reduced. The invention also provides nucleic acids that encode such antibodies. In addition, the invention provides the use of the antibodies of the invention in prophylaxis and treatment of various diseases including multiple sclerosis and Crohn's disease.
IPC codes: A61P   1/    00            A I
A61P  25/    28            A I
C07K  16/    28            A I
Claims: number: 1
text: An antibody, or an antigen-binding fragment thereof, comprising (i) the heavy chain CDR1, CDR2, and CDR3 amino acid sequences as set forth in SEQ ID NO: 1, SEQ ID NO: 2, and SEQ ID NO: 3, respectively, and the light chain CDR1, CDR2, and CDR3 amino acid sequences as set forth in SEQ ID NO: 4, SEQ ID NO: 5, and SEQ ID NO: 6, respectively.
number: 2
text: The antibody, or an antigen-binding fragment thereof, according to claim 1, wherein the antibody, or the antigen-binding fragment thereof, comprises the light chain CDR2 (LCDR2) amino acid sequence as set forth in SEQ ID NO: 7.
number: 3
text: The antibody, or an antigen-binding fragment thereof, according to claim 1 or 2, wherein (i) X<2> in SEQ ID NO: 5 or 7 is selected from G, T, V, K, D and N; and/or (ii) X<4> in SEQ ID NO: 5 or 7 is selected from N, Q, V, I and S.
number: 4
text: The antibody, or an antigen-binding fragment thereof, according to any one of the previous claims, wherein the antibody, or the antigen-binding fragment thereof, comprises the light chain CDR2 (LCDR2) amino acid sequence as set forth in SEQ ID NO: 8.
number: 5
text: The antibody, or an antigen-binding fragment thereof, according to any one of the previous claims, wherein the antibody, or the antigen-binding fragment thereof, comprises the light chain CDR2 (LCDR2) amino acid sequence as set forth in SEQ ID NO: 9 or 10.
number: 6
text: The antibody, or an antigen-binding fragment thereof, according to any one of the previous claims, wherein the antibody, or the antigen-binding fragment thereof, comprises a heavy chain variable region (VH) comprising an amino acid sequence having at least 70% identity to SEQ ID NO: 15 and a light chain variable region (VL) comprising an amino acid sequence having at least 70% identity to SEQ ID NO: 16.
number: 7
text: The antibody, or an antigen-binding fragment thereof, according to any one of the previous claims, wherein the antibody, or the antigen-binding fragment thereof, comprises a heavy chain variable region (VH) comprising the amino acid sequence as set forth in SEQ ID NO: 15 and a light chain variable region (VL) comprising the amino acid sequence as set forth in SEQ ID NO: 19 or 20.
number: 8
text: The antibody, or an antigen-binding fragment thereof, according to any one of the previous claims, wherein the antibody, or the antigen-binding fragment thereof, binds to α4 integrin.
number: 9
text: The antibody, or an antigen-binding fragment thereof, according to any one of the previous claims, wherein the binding affinity of the antibody, or the antigen-binding fragment thereof, to an MHC molecule is decreased in comparison to the binding affinity of natalizumab to the same MHC molecule.
number: 10
text: The antibody, or an antigen-binding fragment thereof, according to any one of the previous claims, wherein the antibody, or the antigen-binding fragment thereof, is a monoclonal antibody, a purified antibody, a single-chain antibody, Fab, Fab', F(ab')2, Fv or scFv.
number: 11
text: The antibody, or an antigen-binding fragment thereof, according to any one of the previous claims for use as a medicament.
number: 12
text: A nucleic acid molecule or a combination of nucleic acid molecules comprising a polynucleotide encoding the antibody, or an antigen-binding fragment thereof, of any one of claims 1 - 10.
number: 13
text: A vector comprising the nucleic acid molecule or the combination of nucleic acid molecules according to claim 12; or a combination of vectors comprising the combination of nucleic acid molecules according to claim 12.
number: 14
text: A cell expressing the antibody, or an antigen-binding fragment thereof, according to any one of claims 1 - 10, or comprising the nucleic acid molecule or the combination of nucleic acid molecules according to claim 12 or the vector or the combination of vectors according to claim 13.
number: 15
text: A pharmaceutical composition comprising the antibody, or an antigen-binding fragment thereof, according to any one of claims 1 - 10, the nucleic acid molecule or the combination or the combination of nucleic acid molecules according to claim 12, the vector or the combination of vectors according to claim 13, or the cell according to claim 14, and, optionally, a pharmaceutically acceptable diluent or carrier.
Office action: search_report, dated 2020-12-30
Rejection reasons: novelty_epc_54
inventive_step_epc_56
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Final disposition: pending (2020-12-30)