JPWO2021110990A5 - - Google Patents
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- JPWO2021110990A5 JPWO2021110990A5 JP2022533579A JP2022533579A JPWO2021110990A5 JP WO2021110990 A5 JPWO2021110990 A5 JP WO2021110990A5 JP 2022533579 A JP2022533579 A JP 2022533579A JP 2022533579 A JP2022533579 A JP 2022533579A JP WO2021110990 A5 JPWO2021110990 A5 JP WO2021110990A5
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- 239000000427 antigen Substances 0.000 claims 30
- 102000036639 antigens Human genes 0.000 claims 30
- 108091007433 antigens Proteins 0.000 claims 30
- 239000012634 fragment Substances 0.000 claims 30
- 125000003275 alpha amino acid group Chemical group 0.000 claims 27
- 102000039446 nucleic acids Human genes 0.000 claims 24
- 108020004707 nucleic acids Proteins 0.000 claims 24
- 150000007523 nucleic acids Chemical class 0.000 claims 24
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims 20
- 239000003814 drug Substances 0.000 claims 20
- 229940124597 therapeutic agent Drugs 0.000 claims 15
- 201000010099 disease Diseases 0.000 claims 12
- 208000035475 disorder Diseases 0.000 claims 8
- 206010028980 Neoplasm Diseases 0.000 claims 7
- 210000004027 cell Anatomy 0.000 claims 6
- 101000942282 Homo sapiens C-type lectin domain family 1 member A Proteins 0.000 claims 5
- 206010057249 Phagocytosis Diseases 0.000 claims 5
- 210000002540 macrophage Anatomy 0.000 claims 5
- 230000008782 phagocytosis Effects 0.000 claims 5
- 210000004881 tumor cell Anatomy 0.000 claims 5
- 229940127089 cytotoxic agent Drugs 0.000 claims 4
- 210000004443 dendritic cell Anatomy 0.000 claims 4
- 238000004519 manufacturing process Methods 0.000 claims 4
- 210000000066 myeloid cell Anatomy 0.000 claims 4
- 230000001338 necrotic effect Effects 0.000 claims 4
- 239000008194 pharmaceutical composition Substances 0.000 claims 4
- 239000002246 antineoplastic agent Substances 0.000 claims 3
- 239000013642 negative control Substances 0.000 claims 3
- 230000000242 pagocytic effect Effects 0.000 claims 3
- 230000002265 prevention Effects 0.000 claims 3
- 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 2
- 206010009944 Colon cancer Diseases 0.000 claims 2
- 208000001333 Colorectal Neoplasms Diseases 0.000 claims 2
- 206010025323 Lymphomas Diseases 0.000 claims 2
- 206010027406 Mesothelioma Diseases 0.000 claims 2
- 208000037581 Persistent Infection Diseases 0.000 claims 2
- 206010040047 Sepsis Diseases 0.000 claims 2
- 239000005557 antagonist Substances 0.000 claims 2
- 201000011510 cancer Diseases 0.000 claims 2
- 239000003795 chemical substances by application Substances 0.000 claims 2
- 150000001875 compounds Chemical class 0.000 claims 2
- 239000002254 cytotoxic agent Substances 0.000 claims 2
- 231100000599 cytotoxic agent Toxicity 0.000 claims 2
- 206010073071 hepatocellular carcinoma Diseases 0.000 claims 2
- 231100000844 hepatocellular carcinoma Toxicity 0.000 claims 2
- 238000000338 in vitro Methods 0.000 claims 2
- 238000001727 in vivo Methods 0.000 claims 2
- 230000006698 induction Effects 0.000 claims 2
- 208000027866 inflammatory disease Diseases 0.000 claims 2
- 239000007788 liquid Substances 0.000 claims 2
- 230000000861 pro-apoptotic effect Effects 0.000 claims 2
- 239000007787 solid Substances 0.000 claims 2
- 108010006654 Bleomycin Proteins 0.000 claims 1
- -1 CAR-T cells) Substances 0.000 claims 1
- CMSMOCZEIVJLDB-UHFFFAOYSA-N Cyclophosphamide Chemical compound ClCCN(CCCl)P1(=O)NCCCO1 CMSMOCZEIVJLDB-UHFFFAOYSA-N 0.000 claims 1
- 108060003951 Immunoglobulin Proteins 0.000 claims 1
- 102000018071 Immunoglobulin Fc Fragments Human genes 0.000 claims 1
- 108010091135 Immunoglobulin Fc Fragments Proteins 0.000 claims 1
- 229960000548 alemtuzumab Drugs 0.000 claims 1
- 229930013930 alkaloid Natural products 0.000 claims 1
- 150000003797 alkaloid derivatives Chemical class 0.000 claims 1
- 230000002152 alkylating effect Effects 0.000 claims 1
- 229940045799 anthracyclines and related substance Drugs 0.000 claims 1
- 239000003242 anti bacterial agent Substances 0.000 claims 1
- 230000000340 anti-metabolite Effects 0.000 claims 1
- 229940044684 anti-microtubule agent Drugs 0.000 claims 1
- 230000001028 anti-proliverative effect Effects 0.000 claims 1
- 229940100197 antimetabolite Drugs 0.000 claims 1
- 239000002256 antimetabolite Substances 0.000 claims 1
- 229940034982 antineoplastic agent Drugs 0.000 claims 1
- 229960003852 atezolizumab Drugs 0.000 claims 1
- 229960000397 bevacizumab Drugs 0.000 claims 1
- 230000003115 biocidal effect Effects 0.000 claims 1
- 229960001561 bleomycin Drugs 0.000 claims 1
- OYVAGSVQBOHSSS-UAPAGMARSA-O bleomycin A2 Chemical compound N([C@H](C(=O)N[C@H](C)[C@@H](O)[C@H](C)C(=O)N[C@@H]([C@H](O)C)C(=O)NCCC=1SC=C(N=1)C=1SC=C(N=1)C(=O)NCCC[S+](C)C)[C@@H](O[C@H]1[C@H]([C@@H](O)[C@H](O)[C@H](CO)O1)O[C@@H]1[C@H]([C@@H](OC(N)=O)[C@H](O)[C@@H](CO)O1)O)C=1N=CNC=1)C(=O)C1=NC([C@H](CC(N)=O)NC[C@H](N)C(N)=O)=NC(N)=C1C OYVAGSVQBOHSSS-UAPAGMARSA-O 0.000 claims 1
- 230000025084 cell cycle arrest Effects 0.000 claims 1
- 229960005395 cetuximab Drugs 0.000 claims 1
- 238000002648 combination therapy Methods 0.000 claims 1
- 229960004397 cyclophosphamide Drugs 0.000 claims 1
- 231100000433 cytotoxic Toxicity 0.000 claims 1
- 230000001472 cytotoxic effect Effects 0.000 claims 1
- 230000004069 differentiation Effects 0.000 claims 1
- 239000003534 dna topoisomerase inhibitor Substances 0.000 claims 1
- 108020001507 fusion proteins Proteins 0.000 claims 1
- 102000037865 fusion proteins Human genes 0.000 claims 1
- 229940022353 herceptin Drugs 0.000 claims 1
- 102000018358 immunoglobulin Human genes 0.000 claims 1
- 229940072221 immunoglobulins Drugs 0.000 claims 1
- 239000002955 immunomodulating agent Substances 0.000 claims 1
- 239000003018 immunosuppressive agent Substances 0.000 claims 1
- 229940125721 immunosuppressive agent Drugs 0.000 claims 1
- 230000001939 inductive effect Effects 0.000 claims 1
- 230000003834 intracellular effect Effects 0.000 claims 1
- 230000000503 lectinlike effect Effects 0.000 claims 1
- 238000011275 oncology therapy Methods 0.000 claims 1
- 229960001972 panitumumab Drugs 0.000 claims 1
- 229920001184 polypeptide Polymers 0.000 claims 1
- 239000006041 probiotic Substances 0.000 claims 1
- 230000000529 probiotic effect Effects 0.000 claims 1
- 235000018291 probiotics Nutrition 0.000 claims 1
- 108090000765 processed proteins & peptides Proteins 0.000 claims 1
- 102000004196 processed proteins & peptides Human genes 0.000 claims 1
- 230000003439 radiotherapeutic effect Effects 0.000 claims 1
- 229960004641 rituximab Drugs 0.000 claims 1
- 230000008685 targeting Effects 0.000 claims 1
- 229940044693 topoisomerase inhibitor Drugs 0.000 claims 1
- 229960000575 trastuzumab Drugs 0.000 claims 1
Claims (22)
・アミノ酸配列がそれぞれ、
- 配列番号57、配列番号65、配列番号73、配列番号81、配列番号89又は配列番号97、特に、配列番号65、配列番号81、又は配列番号97のVHCDR1、及び
- 配列番号59、配列番号67、配列番号75、配列番号83、又は配列番号91、特に、配列番号67、配列番号75、又は配列番号83のVHCDR2、及び
- 配列番号61、配列番号69、配列番号77、配列番号85、又は配列番号93、特に、配列番号69、配列番号77、又は配列番号85のVHCDR3
から選択される3個のVHCDRを含む抗体重鎖可変ドメイン、並びに
・アミノ酸配列が、
- 配列番号4、配列番号12、配列番号20、配列番号28、又は配列番号36、特に、配列番号12、配列番号20、又は配列番号28のVLCDR1、及び
- 配列番号6、配列番号14、配列番号22、配列番号30、又は配列番号38、特に、配列番号14、配列番号22、又は配列番号30のVLCDR2、及び
- 配列番号8、配列番号16、配列番号24、配列番号32、又は配列番号40、特に、配列番号16、配列番号24、又は配列番号32のVLCDR3
から選択される3個のVLCDRを含む抗体軽鎖可変ドメイン
を含む抗体又はその抗原結合性断片。 An antibody or antigen-binding fragment thereof that specifically binds to the extracellular domain of human C-type lectin-like receptor-1 member A receptor (CLEC-1A receptor),
・Each amino acid sequence is
- VHCDR1 of SEQ ID NO: 57, SEQ ID NO: 65, SEQ ID NO: 73, SEQ ID NO: 81, SEQ ID NO: 89 or SEQ ID NO: 97, in particular SEQ ID NO: 65, SEQ ID NO: 81 or SEQ ID NO: 97, and
- VHCDR2 of SEQ ID NO: 59, SEQ ID NO: 67, SEQ ID NO: 75, SEQ ID NO: 83, or SEQ ID NO: 91, in particular SEQ ID NO: 67, SEQ ID NO: 75, or SEQ ID NO: 83, and
- VHCDR3 of SEQ ID NO: 61, SEQ ID NO: 69, SEQ ID NO: 77, SEQ ID NO: 85, or SEQ ID NO: 93, in particular SEQ ID NO: 69, SEQ ID NO: 77, or SEQ ID NO: 85
An antibody heavy chain variable domain comprising three VHCDRs selected from;
- VLCDR1 of SEQ ID NO: 4, SEQ ID NO: 12, SEQ ID NO: 20, SEQ ID NO: 28, or SEQ ID NO: 36, in particular SEQ ID NO: 12, SEQ ID NO: 20, or SEQ ID NO: 28, and
- VLCDR2 of SEQ ID NO: 6, SEQ ID NO: 14, SEQ ID NO: 22, SEQ ID NO: 30, or SEQ ID NO: 38, in particular SEQ ID NO: 14, SEQ ID NO: 22, or SEQ ID NO: 30, and
- VLCDR3 of SEQ ID NO: 8, SEQ ID NO: 16, SEQ ID NO: 24, SEQ ID NO: 32, or SEQ ID NO: 40, in particular SEQ ID NO: 16, SEQ ID NO: 24, or SEQ ID NO: 32
An antibody or an antigen-binding fragment thereof comprising an antibody light chain variable domain comprising three VLCDRs selected from:
・配列番号67、又は配列番号75、又は配列番号83で記載されたアミノ酸配列を含むか又はそれからなるVHCDR2、及び
・配列番号69、又は配列番号77、又は配列番号85で記載されたアミノ酸配列を含むか又はそれからなるVHCDR3、及び
・配列番号12、又は配列番号20、又は配列番号28で記載されたアミノ酸配列を含むか又はそれからなるVLCDR1、及び
・配列番号14、又は配列番号22、又は配列番号30で記載されたアミノ酸配列を含むか又はそれからなるVLCDR2、及び
・配列番号16、又は配列番号24、又は配列番号32で記載されたアミノ酸配列を含むか又はそれからなるVLCDR3
から選択される、少なくとも1個のCDRドメイン、特に、6個のCDRドメインを含む、請求項1に記載の抗体又はその抗原結合性断片。 - VHCDR1 containing or consisting of the amino acid sequence set forth in SEQ ID NO: 65, SEQ ID NO: 81, or SEQ ID NO: 97, and - Containing the amino acid sequence set forth in SEQ ID NO: 67, SEQ ID NO: 75, or SEQ ID NO: 83 VHCDR2 comprising or consisting of the amino acid sequence set forth in SEQ ID NO: 69, or SEQ ID NO: 77, or SEQ ID NO: 85, and - SEQ ID NO: 12, or SEQ ID NO: 20, or SEQ ID NO: 28. VLCDR1 comprising or consisting of the amino acid sequence set forth in SEQ ID NO: 14, or SEQ ID NO: 22, or VLCDR2 comprising or consisting of the amino acid sequence set forth in SEQ ID NO: 30, and - SEQ ID NO: 16, or VLCDR3 comprising or consisting of the amino acid sequence set forth in SEQ ID NO: 24 or SEQ ID NO: 32
2. The antibody or antigen-binding fragment thereof according to claim 1, comprising at least one CDR domain, in particular 6 CDR domains, selected from:
- それぞれ配列番号57、配列番号59、及び配列番号61、又は
- それぞれ配列番号65、配列番号67、及び配列番号69、又は
- それぞれ配列番号73、配列番号75、及び配列番号77、又は
- それぞれ配列番号81、配列番号83、及び配列番号85、又は
- それぞれ配列番号89、配列番号91、及び配列番号93、又は
- それぞれ配列番号97、配列番号75、及び配列番号77
の配列のVHCDR1、VHCDR2、及びVHCDR3を含む、請求項1から3のいずれか一項に記載の抗体又はその抗原結合性断片。 The antibody heavy chain variable domain is
- SEQ ID NO: 57, SEQ ID NO: 59, and SEQ ID NO: 61, respectively, or
- SEQ ID NO: 65, SEQ ID NO: 67, and SEQ ID NO: 69, respectively, or
- SEQ ID NO: 73, SEQ ID NO: 75, and SEQ ID NO: 77, respectively, or
- SEQ ID NO: 81, SEQ ID NO: 83, and SEQ ID NO: 85, respectively, or
- SEQ ID NO: 89, SEQ ID NO: 91, and SEQ ID NO: 93, respectively, or
- SEQ ID NO: 97, SEQ ID NO: 75, and SEQ ID NO: 77, respectively
4. The antibody or antigen-binding fragment thereof according to any one of claims 1 to 3, comprising VHCDR1, VHCDR2, and VHCDR3 of the sequence.
- それぞれ配列番号4、配列番号6、及び配列番号8、又は
- それぞれ配列番号12、配列番号14、及び配列番号16、又は
- それぞれ配列番号20、配列番号22、及び配列番号24、又は
- それぞれ配列番号28、配列番号30、及び配列番号32、又は
- それぞれ配列番号36、配列番号38、及び配列番号40
の配列のVLCDR1、VLCDR2、及びVLCDR3を含む、請求項1から4のいずれか一項に記載の抗体又はその抗原結合性断片。 The antibody light chain variable domain is
- SEQ ID NO: 4, SEQ ID NO: 6, and SEQ ID NO: 8, respectively, or
- SEQ ID NO: 12, SEQ ID NO: 14, and SEQ ID NO: 16, respectively, or
- SEQ ID NO: 20, SEQ ID NO: 22, and SEQ ID NO: 24, respectively, or
- SEQ ID NO: 28, SEQ ID NO: 30, and SEQ ID NO: 32, respectively, or
- SEQ ID NO: 36, SEQ ID NO: 38, and SEQ ID NO: 40, respectively
5. The antibody or antigen-binding fragment thereof according to any one of claims 1 to 4, comprising VLCDR1, VLCDR2, and VLCDR3 of the sequence.
(b)抗体重鎖可変ドメインが、それぞれ配列番号65、配列番号67、及び配列番号69の配列のVHCDR1、VHCDR2、及びVHCDR3を含み、抗体軽鎖可変ドメインが、それぞれ配列番号12、配列番号14、及び配列番号16の配列のVLCDR1、VLCDR2、及びVLCDR3を含むか、又は
(c)抗体重鎖可変ドメインが、それぞれ配列番号73、配列番号75、及び配列番号77の配列のVHCDR1、VHCDR2、及びVHCDR3を含み、抗体軽鎖可変ドメインが、それぞれ配列番号20、配列番号22、及び配列番号24の配列のVLCDR1、VLCDR2、及びVLCDR3を含むか、又は
(d)抗体重鎖可変ドメインが、それぞれ配列番号81、配列番号83、及び配列番号85の配列のVHCDR1、VHCDR2、及びVHCDR3を含み、抗体軽鎖可変ドメインが、それぞれ配列番号28、配列番号30、及び配列番号32の配列のVLCDR1、VLCDR2、及びVLCDR3を含むか、又は
(e)抗体重鎖可変ドメインが、それぞれ配列番号89、配列番号91、及び配列番号93の配列のVHCDR1、VHCDR2、及びVHCDR3を含み、抗体軽鎖可変ドメインが、それぞれ配列番号36、配列番号38、及び配列番号40の配列のVLCDR1、VLCDR2、及びVLCDR3を含むか、又は
(f)抗体重鎖可変ドメインが、それぞれ配列番号97、配列番号75、及び配列番号77の配列のVHCDR1、VHCDR2、及びVHCDR3を含み、抗体軽鎖可変ドメインが、それぞれ配列番号20、配列番号22、及び配列番号24の配列のVLCDR1、VLCDR2、及びVLCDR3を含む、
請求項1から5のいずれか一項に記載の抗体又はその抗原結合性断片。 (a) The antibody heavy chain variable domain comprises VHCDR1, VHCDR2, and VHCDR3 having the sequences of SEQ ID NO: 57, SEQ ID NO: 59, and SEQ ID NO: 61, respectively, and the antibody light chain variable domain includes SEQ ID NO: 4, SEQ ID NO: 6, respectively. , and VLCDR1, VLCDR2, and VLCDR3 of the sequence SEQ ID NO: 8, or
(b) The antibody heavy chain variable domain comprises VHCDR1, VHCDR2, and VHCDR3 having the sequences of SEQ ID NO: 65, SEQ ID NO: 67, and SEQ ID NO: 69, respectively, and the antibody light chain variable domain includes SEQ ID NO: 12, SEQ ID NO: 14, respectively. , and VLCDR1, VLCDR2, and VLCDR3 of the sequence SEQ ID NO: 16, or
(c) The antibody heavy chain variable domain includes VHCDR1, VHCDR2, and VHCDR3 having the sequences of SEQ ID NO: 73, SEQ ID NO: 75, and SEQ ID NO: 77, respectively, and the antibody light chain variable domain includes SEQ ID NO: 20 and SEQ ID NO: 22, respectively. , and VLCDR1, VLCDR2, and VLCDR3 of the sequence SEQ ID NO: 24, or
(d) The antibody heavy chain variable domain comprises VHCDR1, VHCDR2, and VHCDR3 having the sequences of SEQ ID NO: 81, SEQ ID NO: 83, and SEQ ID NO: 85, respectively, and the antibody light chain variable domain includes SEQ ID NO: 28, SEQ ID NO: 30, respectively. , and VLCDR1, VLCDR2, and VLCDR3 of the sequence SEQ ID NO: 32, or
(e) The antibody heavy chain variable domain comprises VHCDR1, VHCDR2, and VHCDR3 having the sequences of SEQ ID NO: 89, SEQ ID NO: 91, and SEQ ID NO: 93, respectively, and the antibody light chain variable domain includes SEQ ID NO: 36, SEQ ID NO: 38, respectively. , and VLCDR1, VLCDR2, and VLCDR3 of the sequence SEQ ID NO: 40, or
(f) The antibody heavy chain variable domain comprises VHCDR1, VHCDR2, and VHCDR3 having the sequences of SEQ ID NO: 97, SEQ ID NO: 75, and SEQ ID NO: 77, respectively, and the antibody light chain variable domain includes SEQ ID NO: 20, SEQ ID NO: 22, respectively. , and containing VLCDR1, VLCDR2, and VLCDR3 of the sequence SEQ ID NO: 24,
The antibody or antigen-binding fragment thereof according to any one of claims 1 to 5.
- 配列番号63で記載されたアミノ酸配列を含むか若しくはそれからなる重鎖可変ドメイン及び配列番号10で記載されたアミノ酸配列を含むか若しくはそれからなる軽鎖可変ドメイン、又は、
- 配列番号71で記載されたアミノ酸配列を含むか若しくはそれからなる重鎖可変ドメイン及び配列番号18で記載されたアミノ酸配列を含むか若しくはそれからなる軽鎖可変ドメイン、又は、
- 配列番号79で記載されたアミノ酸配列を含むか若しくはそれからなる重鎖可変ドメイン及び配列番号26で記載されたアミノ酸配列を含むか若しくはそれからなる軽鎖可変ドメイン、又は、
- 配列番号87で記載されたアミノ酸配列を含むか若しくはそれからなる重鎖可変ドメイン及び配列番号34で記載されたアミノ酸配列を含むか若しくはそれからなる軽鎖可変ドメイン、又は、
- 配列番号95で記載されたアミノ酸配列を含むか若しくはそれからなる重鎖可変ドメイン及び配列番号42で記載されたアミノ酸配列を含むか若しくはそれからなる軽鎖可変ドメイン
を含むか又はそれらからなり、
- より詳細には、重鎖可変ドメインが配列番号95で記載されたアミノ酸配列を含むか若しくはそれからなり、軽鎖可変ドメインが配列番号42で記載されたアミノ酸配列を含むか若しくはそれからなり、又は、重鎖可変ドメインが配列番号63で記載されたアミノ酸配列を含むか若しくはそれからなり、軽鎖可変ドメインが配列番号10で記載されたアミノ酸配列を含むか若しくはそれからなり、又は、重鎖可変ドメインが配列番号79で記載されたアミノ酸配列を含むか若しくはそれからなり、軽鎖可変ドメインが配列番号26で記載されたアミノ酸配列を含むか若しくはそれからなる、請求項1から8のいずれか一項に記載の抗体又はその抗原結合性断片。 - a heavy chain variable domain comprising or consisting of the amino acid sequence set forth in SEQ ID NO: 55 and a light chain variable domain comprising or consisting of the amino acid sequence set forth in SEQ ID NO: 2, or
- a heavy chain variable domain comprising or consisting of the amino acid sequence set forth in SEQ ID NO: 63 and a light chain variable domain comprising or consisting of the amino acid sequence set forth in SEQ ID NO: 10, or
- a heavy chain variable domain comprising or consisting of the amino acid sequence set forth in SEQ ID NO: 71 and a light chain variable domain comprising or consisting of the amino acid sequence set forth in SEQ ID NO: 18, or
- a heavy chain variable domain comprising or consisting of the amino acid sequence set forth in SEQ ID NO: 79 and a light chain variable domain comprising or consisting of the amino acid sequence set forth in SEQ ID NO: 26, or
- a heavy chain variable domain comprising or consisting of the amino acid sequence set forth in SEQ ID NO: 87 and a light chain variable domain comprising or consisting of the amino acid sequence set forth in SEQ ID NO: 34, or
- comprising or consisting of a heavy chain variable domain comprising or consisting of the amino acid sequence set forth in SEQ ID NO: 95 and a light chain variable domain comprising or consisting of the amino acid sequence set forth in SEQ ID NO: 42;
- more particularly, the heavy chain variable domain comprises or consists of the amino acid sequence set out in SEQ ID NO: 95, the light chain variable domain comprises or consists of the amino acid sequence set out in SEQ ID NO: 42, or The heavy chain variable domain comprises or consists of the amino acid sequence set forth in SEQ ID NO: 63, the light chain variable domain comprises or consists of the amino acid sequence set forth in SEQ ID NO: 10, or the heavy chain variable domain comprises or consists of the amino acid sequence set forth in SEQ ID NO: 10; 9. The antibody according to any one of claims 1 to 8, wherein the light chain variable domain comprises or consists of the amino acid sequence set forth in SEQ ID NO: 26. or an antigen-binding fragment thereof.
i)第1の治療薬が、請求項1から12のいずれか一項に記載の抗体若しくはその抗原結合性断片、又は
ヒトC型レクチン様受容体-1メンバーA受容体(CLEC-1A受容体)の細胞外ドメインに特異的に結合し、ヒトCLEC-1A受容体への結合について、配列番号71を含むか若しくはそれからなる重鎖可変ドメイン及び配列番号18を含むか若しくはそれからなる軽鎖可変ドメインを含むか若しくはそれらからなる抗体、特に配列番号121を含むか若しくはそれからなる重鎖ドメイン及び配列番号128を含むか若しくはそれからなる軽鎖ドメインを含むか若しくはそれらからなる抗体と競合し、ヒトCLEC-1のアンタゴニストである抗体若しくはその抗原結合性断片、又は
ヒトC型レクチン様受容体-1メンバーA受容体(CLEC-1A受容体)の細胞外ドメインに特異的に結合し、ヒトCLEC-1A受容体への結合について、配列番号63を含むか若しくはそれからなる重鎖可変ドメイン及び配列番号10を含むか若しくはそれからなる軽鎖可変ドメインを含むか若しくはそれらからなる抗体、特に配列番号120を含むか若しくはそれからなる重鎖ドメイン及び配列番号127を含むか若しくはそれからなる軽鎖ドメインを含むか若しくはそれらからなる抗体と競合し、ヒトCLEC-1のアンタゴニストである抗体若しくはその抗原結合性断片、又は
ヒトC型レクチン様受容体-1メンバーA受容体(CLEC-1A受容体)の細胞外ドメインに特異的に結合し、in vivo及び/若しくはin vitroで使用した場合、陰性対照と比較した、特に陰性対照と比較して少なくとも10%の、骨髄系細胞、特に、樹状細胞及び/若しくはマクロファージによる腫瘍細胞及び/若しくは二次壊死細胞の食作用の調節、特に増加と相関する、抗体若しくはその抗原結合性断片
であり、並びに、
ii)少なくとも1つの第2の治療薬が、特に、第1の治療薬及び第2の治療薬の同時、個別、又は連続使用のために、腫瘍標的化抗体又はその抗原結合性断片、特に腫瘍標的化モノクローナル抗体又はその抗原結合性断片、より詳細には、マクロファージの食作用能力を活性化及び/又は増強する腫瘍標的化モノクローナル抗体又はその抗原結合性断片、更により詳細には、アレムツズマブ、アテゾリズマブ、ベバシズマブ、セツキシマブ、ハーセプチン、パニツムマブ、リツキシマブ、トラスツズマブ、抗PDL-1抗体、及び抗CD47抗体からなる群から選択されるモノクローナル抗体、及び/又は抗PD1抗体及び抗SIRPa抗体からなる群から選択される別の抗体又はモノクローナル抗体、及び/又は化学療法薬、特に抗増殖性、アポトーシス促進性、細胞周期停止、及び/若しくは分化誘導効果を有する細胞毒性剤、より詳細には、細胞毒性抗体、アルキル化剤、アントラサイクリン、代謝拮抗剤、抗微小管剤、トポイソメラーゼ阻害剤、アルカロイド、ブレオマイシン、抗悪性腫瘍薬、シクロホスファミドからなる群から選択される細胞毒性剤からなるリストから選択される、
化合物の組合せ。 A combination of compounds comprising a first therapeutic agent and at least one second therapeutic agent, the combination comprising:
i) The first therapeutic agent is the antibody or antigen-binding fragment thereof according to any one of claims 1 to 12, or human C-type lectin-like receptor-1 member A receptor (CLEC-1A receptor). ) and for binding to the human CLEC-1A receptor, a heavy chain variable domain comprising or consisting of SEQ ID NO: 71 and a light chain variable domain comprising or consisting of SEQ ID NO: 18. 121, and in particular an antibody comprising or consisting of a heavy chain domain comprising or consisting of SEQ ID NO: 128, and a human CLEC- Antibodies or antigen-binding fragments thereof that are antagonists of human C-type lectin-like receptor-1 member A receptor (CLEC-1A receptor), or antibodies that specifically bind to the extracellular domain of human C-type lectin-like receptor-1 member A receptor (CLEC-1A receptor), For binding to the body, an antibody comprising or consisting of a heavy chain variable domain comprising or consisting of SEQ ID NO: 63 and a light chain variable domain comprising or consisting of SEQ ID NO: 10, in particular an antibody comprising or consisting of SEQ ID NO: 120. an antibody or an antigen-binding fragment thereof that is an antagonist of human CLEC-1 and competes with an antibody comprising or consisting of a heavy chain domain consisting of the same and a light chain domain comprising or consisting of SEQ ID NO: 127, or human type C It binds specifically to the extracellular domain of the lectin-like receptor-1 member A receptor (CLEC-1A receptor), and when used in vivo and/or in vitro, is particularly effective when compared to negative controls. Antibodies or antigen-binding fragments thereof that correlate with a modulation, in particular an increase in the phagocytosis of tumor cells and/or secondary necrotic cells by myeloid cells, in particular dendritic cells and/or macrophages, by at least 10% in comparison. and,
ii) the at least one second therapeutic agent is a tumor-targeting antibody or antigen-binding fragment thereof, particularly for simultaneous, separate, or sequential use of the first therapeutic agent and the second therapeutic agent; Targeting monoclonal antibodies or antigen-binding fragments thereof, more particularly tumor-targeting monoclonal antibodies or antigen-binding fragments thereof that activate and/or enhance the phagocytic ability of macrophages, even more particularly alemtuzumab, atezolizumab , a monoclonal antibody selected from the group consisting of bevacizumab, cetuximab, herceptin, panitumumab, rituximab, trastuzumab, an anti-PDL-1 antibody, and an anti-CD47 antibody, and/or a monoclonal antibody selected from the group consisting of an anti-PD1 antibody and an anti-SIRPa antibody. another antibody or monoclonal antibody, and/or a chemotherapeutic agent, in particular a cytotoxic agent with antiproliferative, proapoptotic, cell cycle arrest, and/or differentiation-inducing effects, more particularly a cytotoxic antibody, an alkylating selected from the list consisting of a cytotoxic agent selected from the group consisting of an anthracycline, an antimetabolite, an anti-microtubule agent, a topoisomerase inhibitor, an alkaloid, a bleomycin, an antineoplastic agent, a cyclophosphamide;
combination of compounds.
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| PCT/EP2020/084770 WO2021110990A1 (en) | 2019-12-05 | 2020-12-04 | Anti-clec-1a antibodies and antigen-binding fragment thereof |
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| WO2023083890A1 (en) * | 2021-11-09 | 2023-05-19 | Ose Immunotherapeutics | Identification of clec-1 ligand and uses thereof |
| WO2024028347A1 (en) * | 2022-08-01 | 2024-02-08 | Ose Immunotherapeutics | Heterodimeric fc-clec-1 fusion molecule and uses thereof |
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| EP0739981A1 (en) | 1995-04-25 | 1996-10-30 | Vrije Universiteit Brussel | Variable fragments of immunoglobulins - use for therapeutic or veterinary purposes |
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