NZ756971B2 - Anti human annexin a1 antibody - Google Patents
Anti human annexin a1 antibody Download PDFInfo
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- NZ756971B2 NZ756971B2 NZ756971A NZ75697118A NZ756971B2 NZ 756971 B2 NZ756971 B2 NZ 756971B2 NZ 756971 A NZ756971 A NZ 756971A NZ 75697118 A NZ75697118 A NZ 75697118A NZ 756971 B2 NZ756971 B2 NZ 756971B2
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- specific binding
- sequence set
- binding molecule
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- 101000959738 Homo sapiens Annexin A1 Proteins 0.000 title 1
- 102000051605 human ANXA1 Human genes 0.000 title 1
- 230000009870 specific binding Effects 0.000 claims abstract 40
- 125000003275 alpha amino acid group Chemical group 0.000 claims abstract 16
- 201000010099 disease Diseases 0.000 claims abstract 15
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract 15
- 208000021384 Obsessive-Compulsive disease Diseases 0.000 claims abstract 14
- 210000001744 T-lymphocyte Anatomy 0.000 claims abstract 8
- 230000001404 mediated effect Effects 0.000 claims abstract 8
- 208000023275 Autoimmune disease Diseases 0.000 claims abstract 7
- 208000019901 Anxiety disease Diseases 0.000 claims abstract 6
- FWMNVWWHGCHHJJ-SKKKGAJSSA-N 4-amino-1-[(2r)-6-amino-2-[[(2r)-2-[[(2r)-2-[[(2r)-2-amino-3-phenylpropanoyl]amino]-3-phenylpropanoyl]amino]-4-methylpentanoyl]amino]hexanoyl]piperidine-4-carboxylic acid Chemical compound C([C@H](C(=O)N[C@H](CC(C)C)C(=O)N[C@H](CCCCN)C(=O)N1CCC(N)(CC1)C(O)=O)NC(=O)[C@H](N)CC=1C=CC=CC=1)C1=CC=CC=C1 FWMNVWWHGCHHJJ-SKKKGAJSSA-N 0.000 claims abstract 4
- 206010039073 rheumatoid arthritis Diseases 0.000 claims abstract 3
- 201000000596 systemic lupus erythematosus Diseases 0.000 claims abstract 3
- 238000002560 therapeutic procedure Methods 0.000 claims abstract 2
- 239000008194 pharmaceutical composition Substances 0.000 claims 13
- 238000002360 preparation method Methods 0.000 claims 11
- 239000002773 nucleotide Substances 0.000 claims 9
- 125000003729 nucleotide group Chemical group 0.000 claims 9
- 150000007523 nucleic acids Chemical class 0.000 claims 7
- 102000039446 nucleic acids Human genes 0.000 claims 7
- 108020004707 nucleic acids Proteins 0.000 claims 7
- 239000003814 drug Substances 0.000 claims 5
- 238000000034 method Methods 0.000 claims 4
- 208000019906 panic disease Diseases 0.000 claims 4
- 230000001363 autoimmune Effects 0.000 claims 3
- 230000027455 binding Effects 0.000 claims 3
- 239000012634 fragment Substances 0.000 claims 3
- 208000030507 AIDS Diseases 0.000 claims 2
- 206010000234 Abortion spontaneous Diseases 0.000 claims 2
- 208000036640 Asperger disease Diseases 0.000 claims 2
- 201000006062 Asperger syndrome Diseases 0.000 claims 2
- 201000001320 Atherosclerosis Diseases 0.000 claims 2
- 208000006096 Attention Deficit Disorder with Hyperactivity Diseases 0.000 claims 2
- 208000036864 Attention deficit/hyperactivity disease Diseases 0.000 claims 2
- 208000027496 Behcet disease Diseases 0.000 claims 2
- 208000020925 Bipolar disease Diseases 0.000 claims 2
- 208000032841 Bulimia Diseases 0.000 claims 2
- 206010006550 Bulimia nervosa Diseases 0.000 claims 2
- 208000011688 Generalised anxiety disease Diseases 0.000 claims 2
- 208000009329 Graft vs Host Disease Diseases 0.000 claims 2
- 208000003807 Graves Disease Diseases 0.000 claims 2
- 208000015023 Graves' disease Diseases 0.000 claims 2
- 201000001916 Hypochondriasis Diseases 0.000 claims 2
- 208000022559 Inflammatory bowel disease Diseases 0.000 claims 2
- 206010033664 Panic attack Diseases 0.000 claims 2
- 201000011152 Pemphigus Diseases 0.000 claims 2
- 201000004681 Psoriasis Diseases 0.000 claims 2
- 206010039710 Scleroderma Diseases 0.000 claims 2
- 206010041250 Social phobia Diseases 0.000 claims 2
- 206010052779 Transplant rejections Diseases 0.000 claims 2
- 206010046851 Uveitis Diseases 0.000 claims 2
- 208000015802 attention deficit-hyperactivity disease Diseases 0.000 claims 2
- 210000004027 cell Anatomy 0.000 claims 2
- 208000024908 graft versus host disease Diseases 0.000 claims 2
- 238000000338 in vitro Methods 0.000 claims 2
- 208000015994 miscarriage Diseases 0.000 claims 2
- 201000006417 multiple sclerosis Diseases 0.000 claims 2
- 201000001976 pemphigus vulgaris Diseases 0.000 claims 2
- 201000000980 schizophrenia Diseases 0.000 claims 2
- 208000000995 spontaneous abortion Diseases 0.000 claims 2
- 208000002271 trichotillomania Diseases 0.000 claims 2
- 208000026872 Addison Disease Diseases 0.000 claims 1
- 206010009900 Colitis ulcerative Diseases 0.000 claims 1
- 206010065701 Dermatillomania Diseases 0.000 claims 1
- 208000030836 Hashimoto thyroiditis Diseases 0.000 claims 1
- 102000008394 Immunoglobulin Fragments Human genes 0.000 claims 1
- 108010021625 Immunoglobulin Fragments Proteins 0.000 claims 1
- 241001465754 Metazoa Species 0.000 claims 1
- 208000021386 Sjogren Syndrome Diseases 0.000 claims 1
- 208000013200 Stress disease Diseases 0.000 claims 1
- 208000000323 Tourette Syndrome Diseases 0.000 claims 1
- 208000016620 Tourette disease Diseases 0.000 claims 1
- 201000006704 Ulcerative Colitis Diseases 0.000 claims 1
- 239000013543 active substance Substances 0.000 claims 1
- 208000022266 body dysmorphic disease Diseases 0.000 claims 1
- 239000000969 carrier Substances 0.000 claims 1
- 208000025302 chronic primary adrenal insufficiency Diseases 0.000 claims 1
- 206010009887 colitis Diseases 0.000 claims 1
- 206010012601 diabetes mellitus Diseases 0.000 claims 1
- 239000003085 diluting agent Substances 0.000 claims 1
- 238000004519 manufacturing process Methods 0.000 claims 1
- 239000000546 pharmaceutical excipient Substances 0.000 claims 1
- 208000028173 post-traumatic stress disease Diseases 0.000 claims 1
- 238000000746 purification Methods 0.000 claims 1
- 208000011580 syndromic disease Diseases 0.000 claims 1
- 108010047041 Complementarity Determining Regions Proteins 0.000 abstract 3
Classifications
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- A61K39/395—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
- A61K39/39533—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum against materials from animals
- A61K39/3955—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum against materials from animals against proteinaceous materials, e.g. enzymes, hormones, lymphokines
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- A61K51/04—Organic compounds
- A61K51/08—Peptides, e.g. proteins, carriers being peptides, polyamino acids, proteins
- A61K51/087—Peptides, e.g. proteins, carriers being peptides, polyamino acids, proteins the peptide being an annexin, e.g. annexin V
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/20—Immunoglobulins specific features characterized by taxonomic origin
- C07K2317/24—Immunoglobulins specific features characterized by taxonomic origin containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
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- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
- C07K2317/56—Immunoglobulins specific features characterized by immunoglobulin fragments variable (Fv) region, i.e. VH and/or VL
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
- C07K2317/56—Immunoglobulins specific features characterized by immunoglobulin fragments variable (Fv) region, i.e. VH and/or VL
- C07K2317/565—Complementarity determining region [CDR]
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/90—Immunoglobulins specific features characterized by (pharmaco)kinetic aspects or by stability of the immunoglobulin
- C07K2317/92—Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value
Abstract
The present invention relates to an isolated specific binding molecule which binds human Anx-A1and comprises the complementarity-determining regions (CDRs) VLCDR1, VLCDR2, VLCDR3, VHCDR1, VHCDR2 and VHCDR3, wherein each of said CDRs has an amino acid sequence as follows: VLCDR1 has the sequence set forth in SEQ ID NO: 1, 36 or 37; VLCDR2 has the sequence set forth in SEQ ID NO: 2; VLCDR3 has the sequence set forth in SEQ ID NO: 3; VHCDR1 has the sequence set forth in SEQ ID NO: 4; VHCDR2 has the sequence set forth in SEQ ID NO: 5; and VHCDR3 has the sequence set forth in SEQ ID NO: 6. The specific binding molecule disclosed is therapeutically useful and in particular may be used in therapy for T-cell mediated diseases, including autoimmune diseases such as rheumatoid arthritis and systemic lupus erythematosus, obsessive compulsive disorder (OCD),and OCD-related diseases, such as anxiety disorders.
Claims (40)
1. An isolated specific binding molecule which binds human Anx-A1, said specific binding molecule comprising the complementarity-determining s (CDRs) VLCDR1, VLCDR2, VLCDR3, VHCDR1, VHCDR2 and VHCDR3, wherein each of said CDRs has an amino acid sequence as follows: VLCDR1 has the sequence set forth in SEQ ID NO: 1, 36 or 37; VLCDR2 has the sequence set forth in SEQ ID NO: 2; VLCDR3 has the sequence set forth in SEQ ID NO: 3; VHCDR1 has the sequence set forth in SEQ ID NO: 4; VHCDR2 has the ce set forth in SEQ ID NO: 5; and VHCDR3 has the sequence set forth in SEQ ID NO: 6.
2. The specific g molecule of claim 1, wherein: VLCDR1 has the ce set forth in SEQ ID NO: 1 or 37; VLCDR2 has the sequence set forth in SEQ ID NO: 2; VLCDR3 has the sequence set forth in SEQ ID NO: 3; VHCDR1 has the ce set forth in SEQ ID NO: 4; VHCDR2 has the sequence set forth in SEQ ID NO: 5; and VHCDR3 has the sequence set forth in SEQ ID NO: 6.
3. The specific binding molecule of claim 1, wherein: VLCDR1 has the sequence set forth in SEQ ID NO: 36; VLCDR2 has the sequence set forth in SEQ ID NO: 2; VLCDR3 has the sequence set forth in SEQ ID NO: 3; VHCDR1 has the sequence set forth in SEQ ID NO: 4; VHCDR2 has the sequence set forth in SEQ ID NO: 5; and VHCDR3 has the sequence set forth in SEQ ID NO: 6.
4. The specific binding molecule of any one of claims 1 to 3, wherein the specific binding molecule is an antibody or a fragment f.
5. The specific binding molecule of claim 4, wherein the antibody or nt thereof is humanised.
6. The specific binding molecule of claim 4 or 5, wherein said specific binding molecule is a monoclonal antibody.
7. The specific binding molecule of claim 4 or 5, wherein said specific binding molecule is a fragment of an dy selected from a Fab or F(ab’)2 antibody fragment or an scFv molecule.
8. The specific binding molecule of any one of claims 1 to 7, wherein the Kd of the binding of said specific binding molecule to human Anx-A1 is less than 20 nM.
9. The specific binding molecule of claim 6 or 7, wherein the antibody or fragment thereof comprises: (i) a light chain variable region sing the amino acid sequence set forth in SEQ ID NO: 32, 34 or 48-51, or an amino acid sequence having at least 70 % sequence identity thereto; and (ii) a heavy chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 33 or 35, or an amino acid sequence having at least 70 % ce identity thereto.
10. The specific binding molecule of claim 9, wherein said specific binding molecule is a monoclonal antibody sing: (i) a light chain comprising the amino acid sequence set forth in SEQ ID NO: 40, 44, 46, 54, 75 or 76, or an amino acid sequence having at least 70 % sequence identity thereto; (ii) a heavy chain comprising the amino acid sequence set forth in SEQ ID NO: 41 or 55, or an amino acid sequence having at least 70 % sequence identity thereto.
11. The ic binding molecule of claim 10, n the monoclonal antibody comprises a light chain comprising the amino acid sequence set forth in SEQ ID NO: 40; and a heavy chain comprising the amino acid sequence set forth in SEQ ID NO: 41.
12. The specific binding le of claim 10, wherein the monoclonal antibody comprises a light chain comprising the amino acid sequence set forth in SEQ ID NO: 54; and a heavy chain comprising the amino acid sequence set forth in SEQ ID NO: 55.
13. The specific binding molecule of claim 12, wherein the monoclonal antibody comprises a light chain comprising the amino acid sequence set forth in SEQ ID NO: 44; and a heavy chain sing the amino acid sequence set forth in SEQ ID NO: 41.
14. A preparation containing the specific binding molecule of any one of claims 1 to 13, wherein at least 90 % of the specific binding molecules in the preparation that bind to human Anx-A1 bind with a Kd of less than 20 nM.
15. A nucleic acid molecule comprising a nucleotide sequence encoding a ic binding le as d in any one of claims 1 to 13.
16. The nucleic acid molecule of claim 15, wherein the nucleotide sequence comprises: the nucleotide sequence set forth in SEQ ID NO: 20, 65, 66 or 85-88 which encodes VLCDR1; the nucleotide sequence set forth in SEQ ID NO: 21 or 67 which encodes ; the nucleotide sequence set forth in SEQ ID NO: 22, 68 or 69 which encodes VLCDR3; the nucleotide sequence set forth in SEQ ID NO: 23, 70 or 71 which s the nucleotide sequence set forth in SEQ ID NO: 24 or 72 which encodes VHCDR2; the nucleotide sequence set forth in SEQ ID NO: 25, 73 or 74 which encodes VHCDR3; or, for each sequence, a nucleotide sequence which is degenerate thereto or has at least 85 % sequence identity thereto.
17. A construct comprising the nucleic acid molecule of claim 15 or 16.
18. A vector comprising the nucleic acid molecule of claim 15 or 16 or the construct of claim 17.
19. An in vitro or ex vivo host cell comprising the nucleic acid le of claim 15 or 16, the construct of claim 17 or the vector of claim 18.
20. A method of ing a specific binding molecule as defined in any one of claims 1 to 13 comprising: i) introducing into an in vitro or ex vivo host cell a nucleic acid molecule as defined in claim 15 or 16, a construct as defined in claim 17 or a vector as defined in claim 18; ii) expressing the nucleic acid molecule such that the specific binding molecule is produced; and iii) ting the specific binding molecule.
21. The method of claim 20, wherein said specific binding le is collected by purification.
22. A pharmaceutical composition comprising a specific binding molecule as d in any one of claims 1 to 13, or a preparation as defined in claim 14, and one or more pharmaceutically acceptable diluents, carriers or excipients.
23. The pharmaceutical composition of claim 22, wherein the ic g le is as defined in any one of claims 9 to 13.
24. The pharmaceutical ition of claim 22 or 23, r comprising at least one second therapeutically active agent.
25. A specific binding molecule as defined in any one of claims 1 to 13, a preparation as defined in claim 14 or a pharmaceutical composition as defined in any one of claims 22 to 24 for use in therapy.
26. The specific binding molecule or pharmaceutical composition for use according to claim 25, wherein the specific binding le is as defined in any one of claims 9 to 13 or the pharmaceutical composition is as d in claim 23.
27. A specific binding molecule as defined in any one of claims 1 to 13, a preparation as defined in claim 14 or a pharmaceutical composition as defined in any one of claims 22 to 24 for use in the ent of a T-cell mediated disease, obsessive compulsive disorder (OCD) or an OCD-related disease.
28. The specific binding molecule, preparation or pharmaceutical composition for use according to claim 27, wherein the specific binding molecule is as defined in any one of claims 9 to 13 or the pharmaceutical ition is as defined in claim 23.
29. The specific binding le, preparation or pharmaceutical composition for use according to claim 27 or 28, said use being in the treatment of a T-cell mediated disease, wherein said T-cell mediated disease is an autoimmune disease, graft-versus-host disease, graft rejection, atherosclerosis, miscarriage or HIV/AIDS.
30. The specific binding molecule, preparation or pharmaceutical composition for use according to claim 29, said use being in the treatment of an autoimmune disease, wherein said autoimmune disease is rheumatoid arthritis, multiple sclerosis, systemic lupus erythematosus, Addison’s disease, Grave’s disease, scleroderma, polymyositosis, diabetes, autoimmune uveoretinitis, ulcerative colitis, pemphigus vulgaris, inflammatory bowel disease, autoimmune thyroiditis, uveitis, Behçet’s disease, Sjögren’s me or psoriasis.
31. The specific binding molecule, ation or pharmaceutical composition for use according to claim 27 or 28, said use being in the treatment of an OCD-related disease, wherein said OCD-related e is trichotillomania, illomania, te’s syndrome, Asperger’s syndrome, ia, bulimia, depression, bipolar disorder, hypochondriasis, an anxiety disorder, schizophrenia, attention deficit hyperactivity disorder or body dysmorphic
32. The specific binding molecule, preparation or pharmaceutical composition for use according to claim 31, wherein said anxiety disorder is post-traumatic stress disorder, social anxiety disorder, generalised anxiety disorder, panic disorder or panic attacks.
33. Use of a specific binding molecule as defined in any one of claims 1 to 13, or a preparation as d in claim 14, in the manufacture of a medicament for use in the ent of a T-cell mediated disease, obsessive compulsive disorder (OCD) or an OCD- related disease.
34. The use of claim 33, wherein the specific binding molecule is as d in any one of claims 9 to 13.
35. The use of claim 33 or 34, wherein said medicament is for use in the treatment of a T-cell mediated disease, and said T-cell mediated e is an autoimmune disease, graftversus-host disease, graft rejection, atherosclerosis, miscarriage or HIV/AIDS.
36. The use of claim 35, wherein said medicament is for use in the treatment of an autoimmune disease, and said autoimmune disease is rheumatoid arthritis, multiple sclerosis, systemic lupus erythematosus, n’s disease, Grave’s disease, scleroderma, polymyositosis, es, autoimmune uveoretinitis, tive colitis, pemphigus vulgaris, inflammatory bowel disease, autoimmune ditis, uveitis, Behçet’s disease, Sjögren’s syndrome or psoriasis.
37. The use of claim 33 or 34, wherein said medicament is for use in the treatment of an OCD-related disease, and said OCD-related disease is trichotillomania, dermatillomania, Tourette’s syndrome, Asperger’s syndrome, ia, bulimia, depression, bipolar disorder, hypochondriasis, an anxiety disorder, schizophrenia, attention deficit hyperactivity disorder or body dysmorphic disorder.
38. The use of claim 37, wherein said medicament is for use in the treatment of an anxiety disorder, and said anxiety disorder is raumatic stress disorder, social anxiety disorder, generalised anxiety disorder, panic disorder or panic attacks.
39. A method of treating a T-cell mediated disease, OCD or an OCD-related disease in a non-human animal, comprising stering to the animal a specific binding le as d in any one of claims 1 to 13, a preparation as defined in claim 14 or a pharmaceutical composition as defined in any one of claims 22 to 24.
40. The method of claim 39, wherein the specific binding le is as defined in any one of claims 9 to 13 or the pharmaceutical composition is as defined in claim 23. Hood 2.59.: mucou Hoood Hoax—u.)— Hooood HOOOOOd O Hooooood 959“. F<-é< 2.53 F<¢e< 2: 2: _>_: on 8 <_>_CM\<§1§1>>} Egg]: oom g; ,1, . com erssazezfs 9:: ,,,,,,, 313,2: N .\.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GBGB1702091.8A GB201702091D0 (en) | 2017-02-08 | 2017-02-08 | Specific binding molecules |
| PCT/EP2018/053232 WO2018146230A1 (en) | 2017-02-08 | 2018-02-08 | Anti human annexin a1 antibody |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| NZ756971A NZ756971A (en) | 2023-11-24 |
| NZ756971B2 true NZ756971B2 (en) | 2024-02-27 |
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