AU2020351234A1 - Compositions and methods related to engineered Fc-antigen binding domain constructs targeted to CD38 - Google Patents
Compositions and methods related to engineered Fc-antigen binding domain constructs targeted to CD38 Download PDFInfo
- Publication number
- AU2020351234A1 AU2020351234A1 AU2020351234A AU2020351234A AU2020351234A1 AU 2020351234 A1 AU2020351234 A1 AU 2020351234A1 AU 2020351234 A AU2020351234 A AU 2020351234A AU 2020351234 A AU2020351234 A AU 2020351234A AU 2020351234 A1 AU2020351234 A1 AU 2020351234A1
- Authority
- AU
- Australia
- Prior art keywords
- domain
- monomer
- polypeptide
- amino acid
- domain monomer
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
- 230000027455 binding Effects 0.000 title claims abstract description 606
- 101000777636 Homo sapiens ADP-ribosyl cyclase/cyclic ADP-ribose hydrolase 1 Proteins 0.000 title claims abstract description 362
- 102100031585 ADP-ribosyl cyclase/cyclic ADP-ribose hydrolase 1 Human genes 0.000 title claims abstract description 357
- 239000000427 antigen Substances 0.000 title claims abstract description 241
- 238000000034 method Methods 0.000 title claims abstract description 42
- 239000000203 mixture Substances 0.000 title claims description 32
- 239000000178 monomer Substances 0.000 claims abstract description 1195
- 108090000765 processed proteins & peptides Proteins 0.000 claims abstract description 651
- 102000004196 processed proteins & peptides Human genes 0.000 claims abstract description 600
- 229920001184 polypeptide Polymers 0.000 claims abstract description 586
- 125000003275 alpha amino acid group Chemical group 0.000 claims abstract description 221
- 238000006467 substitution reaction Methods 0.000 claims abstract description 168
- 238000005734 heterodimerization reaction Methods 0.000 claims abstract description 45
- 150000001413 amino acids Chemical group 0.000 claims description 225
- 101100454807 Caenorhabditis elegans lgg-1 gene Proteins 0.000 claims description 146
- 238000005304 joining Methods 0.000 claims description 57
- 102000036639 antigens Human genes 0.000 claims description 46
- 108091007433 antigens Proteins 0.000 claims description 45
- 230000001225 therapeutic effect Effects 0.000 claims description 20
- 238000011282 treatment Methods 0.000 claims description 11
- 230000001404 mediated effect Effects 0.000 claims description 8
- 206010028980 Neoplasm Diseases 0.000 claims description 7
- 206010035226 Plasma cell myeloma Diseases 0.000 claims description 7
- 208000034578 Multiple myelomas Diseases 0.000 claims description 5
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 3
- 206010009944 Colon cancer Diseases 0.000 claims description 2
- 229960002204 daratumumab Drugs 0.000 claims description 2
- 208000035475 disorder Diseases 0.000 claims description 2
- 201000011510 cancer Diseases 0.000 claims 4
- 206010028417 myasthenia gravis Diseases 0.000 claims 3
- 208000023275 Autoimmune disease Diseases 0.000 claims 2
- 206010049567 Miller Fisher syndrome Diseases 0.000 claims 2
- 208000009525 Myocarditis Diseases 0.000 claims 2
- 206010053869 POEMS syndrome Diseases 0.000 claims 2
- 201000011152 Pemphigus Diseases 0.000 claims 2
- 208000033808 peripheral neuropathy Diseases 0.000 claims 2
- 208000023761 AL amyloidosis Diseases 0.000 claims 1
- 206010056508 Acquired epidermolysis bullosa Diseases 0.000 claims 1
- 208000024893 Acute lymphoblastic leukemia Diseases 0.000 claims 1
- 208000014697 Acute lymphocytic leukaemia Diseases 0.000 claims 1
- 208000031261 Acute myeloid leukaemia Diseases 0.000 claims 1
- 208000021769 Acute sensory ataxic neuropathy Diseases 0.000 claims 1
- 208000026872 Addison Disease Diseases 0.000 claims 1
- 206010001881 Alveolar proteinosis Diseases 0.000 claims 1
- 208000010839 B-cell chronic lymphocytic leukemia Diseases 0.000 claims 1
- 206010006187 Breast cancer Diseases 0.000 claims 1
- 208000026310 Breast neoplasm Diseases 0.000 claims 1
- 229940124295 CD38 monoclonal antibody Drugs 0.000 claims 1
- 206010062746 Carditis Diseases 0.000 claims 1
- 208000005024 Castleman disease Diseases 0.000 claims 1
- 206010012468 Dermatitis herpetiformis Diseases 0.000 claims 1
- 208000003556 Dry Eye Syndromes Diseases 0.000 claims 1
- 208000016937 Extranodal nasal NK/T cell lymphoma Diseases 0.000 claims 1
- 206010018364 Glomerulonephritis Diseases 0.000 claims 1
- 206010018372 Glomerulonephritis membranous Diseases 0.000 claims 1
- 208000024869 Goodpasture syndrome Diseases 0.000 claims 1
- 208000003807 Graves Disease Diseases 0.000 claims 1
- 208000015023 Graves' disease Diseases 0.000 claims 1
- 208000035895 Guillain-Barré syndrome Diseases 0.000 claims 1
- 208000002250 Hematologic Neoplasms Diseases 0.000 claims 1
- 208000035186 Hemolytic Autoimmune Anemia Diseases 0.000 claims 1
- 206010019939 Herpes gestationis Diseases 0.000 claims 1
- 208000005531 Immunoglobulin Light-chain Amyloidosis Diseases 0.000 claims 1
- 208000000209 Isaacs syndrome Diseases 0.000 claims 1
- 206010058467 Lung neoplasm malignant Diseases 0.000 claims 1
- 208000031422 Lymphocytic Chronic B-Cell Leukemia Diseases 0.000 claims 1
- 208000025205 Mantle-Cell Lymphoma Diseases 0.000 claims 1
- 206010060880 Monoclonal gammopathy Diseases 0.000 claims 1
- 206010028424 Myasthenic syndrome Diseases 0.000 claims 1
- 208000033776 Myeloid Acute Leukemia Diseases 0.000 claims 1
- 206010028811 Natural killer-cell leukaemia Diseases 0.000 claims 1
- 206010072359 Neuromyotonia Diseases 0.000 claims 1
- 206010034277 Pemphigoid Diseases 0.000 claims 1
- 208000008223 Pemphigoid Gestationis Diseases 0.000 claims 1
- 208000027086 Pemphigus foliaceus Diseases 0.000 claims 1
- 208000007452 Plasmacytoma Diseases 0.000 claims 1
- 208000006664 Precursor Cell Lymphoblastic Leukemia-Lymphoma Diseases 0.000 claims 1
- 208000021386 Sjogren Syndrome Diseases 0.000 claims 1
- 206010072148 Stiff-Person syndrome Diseases 0.000 claims 1
- 208000005718 Stomach Neoplasms Diseases 0.000 claims 1
- 208000031981 Thrombocytopenic Idiopathic Purpura Diseases 0.000 claims 1
- 206010052779 Transplant rejections Diseases 0.000 claims 1
- 208000002552 acute disseminated encephalomyelitis Diseases 0.000 claims 1
- 230000001154 acute effect Effects 0.000 claims 1
- 208000027137 acute motor axonal neuropathy Diseases 0.000 claims 1
- 208000015230 aggressive NK-cell leukemia Diseases 0.000 claims 1
- 201000005000 autoimmune gastritis Diseases 0.000 claims 1
- 201000000448 autoimmune hemolytic anemia Diseases 0.000 claims 1
- 201000003710 autoimmune thrombocytopenic purpura Diseases 0.000 claims 1
- 208000000594 bullous pemphigoid Diseases 0.000 claims 1
- 230000001684 chronic effect Effects 0.000 claims 1
- 208000032852 chronic lymphocytic leukemia Diseases 0.000 claims 1
- 208000025302 chronic primary adrenal insufficiency Diseases 0.000 claims 1
- 208000029742 colonic neoplasm Diseases 0.000 claims 1
- 201000010099 disease Diseases 0.000 claims 1
- 201000006569 extramedullary plasmacytoma Diseases 0.000 claims 1
- 206010017758 gastric cancer Diseases 0.000 claims 1
- 208000025750 heavy chain disease Diseases 0.000 claims 1
- 208000021646 inflammation of heart layer Diseases 0.000 claims 1
- 201000005202 lung cancer Diseases 0.000 claims 1
- 208000020816 lung neoplasm Diseases 0.000 claims 1
- 201000008350 membranous glomerulonephritis Diseases 0.000 claims 1
- 231100000855 membranous nephropathy Toxicity 0.000 claims 1
- 201000005328 monoclonal gammopathy of uncertain significance Diseases 0.000 claims 1
- 201000006417 multiple sclerosis Diseases 0.000 claims 1
- 201000003631 narcolepsy Diseases 0.000 claims 1
- 206010057887 neonatal lupus erythematosus Diseases 0.000 claims 1
- 208000008795 neuromyelitis optica Diseases 0.000 claims 1
- 201000001119 neuropathy Diseases 0.000 claims 1
- 230000007823 neuropathy Effects 0.000 claims 1
- 201000005737 orchitis Diseases 0.000 claims 1
- 201000009234 osteosclerotic myeloma Diseases 0.000 claims 1
- 201000004535 ovarian dysfunction Diseases 0.000 claims 1
- 201000001976 pemphigus vulgaris Diseases 0.000 claims 1
- 208000031223 plasma cell leukemia Diseases 0.000 claims 1
- 201000003489 pulmonary alveolar proteinosis Diseases 0.000 claims 1
- 206010039073 rheumatoid arthritis Diseases 0.000 claims 1
- 201000011549 stomach cancer Diseases 0.000 claims 1
- 235000001014 amino acid Nutrition 0.000 description 340
- 230000035772 mutation Effects 0.000 description 184
- 238000006471 dimerization reaction Methods 0.000 description 84
- 230000002441 reversible effect Effects 0.000 description 82
- 125000006850 spacer group Chemical group 0.000 description 81
- 210000004027 cell Anatomy 0.000 description 80
- 230000004048 modification Effects 0.000 description 50
- 238000012986 modification Methods 0.000 description 50
- 102000004169 proteins and genes Human genes 0.000 description 46
- 108090000623 proteins and genes Proteins 0.000 description 46
- 235000018102 proteins Nutrition 0.000 description 45
- 230000000295 complement effect Effects 0.000 description 41
- 108010047041 Complementarity Determining Regions Proteins 0.000 description 40
- 230000004540 complement-dependent cytotoxicity Effects 0.000 description 31
- JARGNLJYKBUKSJ-KGZKBUQUSA-N (2r)-2-amino-5-[[(2r)-1-(carboxymethylamino)-3-hydroxy-1-oxopropan-2-yl]amino]-5-oxopentanoic acid;hydrobromide Chemical compound Br.OC(=O)[C@H](N)CCC(=O)N[C@H](CO)C(=O)NCC(O)=O JARGNLJYKBUKSJ-KGZKBUQUSA-N 0.000 description 29
- 108010044804 gamma-glutamyl-seryl-glycine Proteins 0.000 description 29
- 230000000694 effects Effects 0.000 description 28
- 230000005888 antibody-dependent cellular phagocytosis Effects 0.000 description 26
- 125000003630 glycyl group Chemical group [H]N([H])C([H])([H])C(*)=O 0.000 description 26
- 150000007523 nucleic acids Chemical class 0.000 description 26
- 230000015572 biosynthetic process Effects 0.000 description 23
- 238000000746 purification Methods 0.000 description 23
- 230000010056 antibody-dependent cellular cytotoxicity Effects 0.000 description 22
- 239000008194 pharmaceutical composition Substances 0.000 description 22
- OTMSDBZUPAUEDD-UHFFFAOYSA-N Ethane Chemical compound CC OTMSDBZUPAUEDD-UHFFFAOYSA-N 0.000 description 21
- 125000000539 amino acid group Chemical group 0.000 description 21
- 102100027211 Albumin Human genes 0.000 description 20
- 108010088751 Albumins Proteins 0.000 description 20
- 239000000126 substance Substances 0.000 description 19
- 210000004881 tumor cell Anatomy 0.000 description 18
- 230000003993 interaction Effects 0.000 description 17
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Natural products NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 16
- 238000004458 analytical method Methods 0.000 description 16
- 210000004899 c-terminal region Anatomy 0.000 description 16
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 16
- 230000002349 favourable effect Effects 0.000 description 15
- 230000006870 function Effects 0.000 description 15
- 102000039446 nucleic acids Human genes 0.000 description 15
- 108020004707 nucleic acids Proteins 0.000 description 15
- 239000004471 Glycine Substances 0.000 description 14
- 210000003719 b-lymphocyte Anatomy 0.000 description 14
- 238000012217 deletion Methods 0.000 description 14
- 230000037430 deletion Effects 0.000 description 14
- -1 e.g. Proteins 0.000 description 14
- 239000012634 fragment Substances 0.000 description 14
- 238000003556 assay Methods 0.000 description 13
- 239000012636 effector Substances 0.000 description 13
- 230000014509 gene expression Effects 0.000 description 13
- 210000004369 blood Anatomy 0.000 description 12
- 239000008280 blood Substances 0.000 description 12
- 239000000539 dimer Substances 0.000 description 12
- 239000003814 drug Substances 0.000 description 12
- 125000003588 lysine group Chemical group [H]N([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])(N([H])[H])C(*)=O 0.000 description 12
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 10
- 239000004472 Lysine Substances 0.000 description 10
- 230000004071 biological effect Effects 0.000 description 10
- 102000009109 Fc receptors Human genes 0.000 description 9
- 108010087819 Fc receptors Proteins 0.000 description 9
- 229940079593 drug Drugs 0.000 description 9
- 108020001580 protein domains Proteins 0.000 description 9
- 101100217502 Caenorhabditis elegans lgg-3 gene Proteins 0.000 description 8
- 108010054477 Immunoglobulin Fab Fragments Proteins 0.000 description 8
- 102000001706 Immunoglobulin Fab Fragments Human genes 0.000 description 8
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 8
- 230000003013 cytotoxicity Effects 0.000 description 8
- 231100000135 cytotoxicity Toxicity 0.000 description 8
- 230000001419 dependent effect Effects 0.000 description 8
- 241000282693 Cercopithecidae Species 0.000 description 7
- 108060003951 Immunoglobulin Proteins 0.000 description 7
- 101710145752 Serine recombinase gin Proteins 0.000 description 7
- 230000006037 cell lysis Effects 0.000 description 7
- 102000018358 immunoglobulin Human genes 0.000 description 7
- 210000002540 macrophage Anatomy 0.000 description 7
- 210000002966 serum Anatomy 0.000 description 7
- HVLSXIKZNLPZJJ-TXZCQADKSA-N HA peptide Chemical compound C([C@@H](C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](C(C)C)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H](C)C(O)=O)NC(=O)[C@H]1N(CCC1)C(=O)[C@@H](N)CC=1C=CC(O)=CC=1)C1=CC=C(O)C=C1 HVLSXIKZNLPZJJ-TXZCQADKSA-N 0.000 description 6
- 102100026120 IgG receptor FcRn large subunit p51 Human genes 0.000 description 6
- 239000002202 Polyethylene glycol Substances 0.000 description 6
- 238000007792 addition Methods 0.000 description 6
- 230000021615 conjugation Effects 0.000 description 6
- 230000000875 corresponding effect Effects 0.000 description 6
- 230000003247 decreasing effect Effects 0.000 description 6
- 102000037865 fusion proteins Human genes 0.000 description 6
- 108020001507 fusion proteins Proteins 0.000 description 6
- 210000004180 plasmocyte Anatomy 0.000 description 6
- 229920001223 polyethylene glycol Polymers 0.000 description 6
- 239000000047 product Substances 0.000 description 6
- 102000005962 receptors Human genes 0.000 description 6
- 108020003175 receptors Proteins 0.000 description 6
- NFGXHKASABOEEW-UHFFFAOYSA-N 1-methylethyl 11-methoxy-3,7,11-trimethyl-2,4-dodecadienoate Chemical compound COC(C)(C)CCCC(C)CC=CC(C)=CC(=O)OC(C)C NFGXHKASABOEEW-UHFFFAOYSA-N 0.000 description 5
- XZWYTXMRWQJBGX-VXBMVYAYSA-N FLAG peptide Chemical compound NCCCC[C@@H](C(O)=O)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CCCCN)NC(=O)[C@@H](NC(=O)[C@@H](N)CC(O)=O)CC1=CC=C(O)C=C1 XZWYTXMRWQJBGX-VXBMVYAYSA-N 0.000 description 5
- SHZGCJCMOBCMKK-DHVFOXMCSA-N L-fucopyranose Chemical compound C[C@@H]1OC(O)[C@@H](O)[C@H](O)[C@@H]1O SHZGCJCMOBCMKK-DHVFOXMCSA-N 0.000 description 5
- 230000004989 O-glycosylation Effects 0.000 description 5
- 101100533506 Schizosaccharomyces pombe (strain 972 / ATCC 24843) sif1 gene Proteins 0.000 description 5
- 210000001185 bone marrow Anatomy 0.000 description 5
- 125000000151 cysteine group Chemical group N[C@@H](CS)C(=O)* 0.000 description 5
- 239000000833 heterodimer Substances 0.000 description 5
- 102000052645 human CD38 Human genes 0.000 description 5
- 239000007924 injection Substances 0.000 description 5
- 238000002347 injection Methods 0.000 description 5
- 238000001990 intravenous administration Methods 0.000 description 5
- 238000004519 manufacturing process Methods 0.000 description 5
- 229920000642 polymer Polymers 0.000 description 5
- 238000002198 surface plasmon resonance spectroscopy Methods 0.000 description 5
- 239000013638 trimer Substances 0.000 description 5
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 5
- 229920000936 Agarose Polymers 0.000 description 4
- SRBFZHDQGSBBOR-IOVATXLUSA-N D-xylopyranose Chemical compound O[C@@H]1COC(O)[C@H](O)[C@H]1O SRBFZHDQGSBBOR-IOVATXLUSA-N 0.000 description 4
- 108020004414 DNA Proteins 0.000 description 4
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 4
- 101000878602 Homo sapiens Immunoglobulin alpha Fc receptor Proteins 0.000 description 4
- 101000917826 Homo sapiens Low affinity immunoglobulin gamma Fc region receptor II-a Proteins 0.000 description 4
- 101000917824 Homo sapiens Low affinity immunoglobulin gamma Fc region receptor II-b Proteins 0.000 description 4
- 108010073816 IgE Receptors Proteins 0.000 description 4
- 102000009438 IgE Receptors Human genes 0.000 description 4
- 102100038005 Immunoglobulin alpha Fc receptor Human genes 0.000 description 4
- 102100029204 Low affinity immunoglobulin gamma Fc region receptor II-a Human genes 0.000 description 4
- 206010025323 Lymphomas Diseases 0.000 description 4
- 206010057249 Phagocytosis Diseases 0.000 description 4
- 238000004113 cell culture Methods 0.000 description 4
- 239000006143 cell culture medium Substances 0.000 description 4
- 230000022534 cell killing Effects 0.000 description 4
- 238000006243 chemical reaction Methods 0.000 description 4
- 239000012228 culture supernatant Substances 0.000 description 4
- 230000009089 cytolysis Effects 0.000 description 4
- 231100000673 dose–response relationship Toxicity 0.000 description 4
- 238000000684 flow cytometry Methods 0.000 description 4
- 125000000524 functional group Chemical group 0.000 description 4
- 150000002333 glycines Chemical class 0.000 description 4
- 239000002773 nucleotide Substances 0.000 description 4
- 125000003729 nucleotide group Chemical group 0.000 description 4
- 230000037361 pathway Effects 0.000 description 4
- 230000008782 phagocytosis Effects 0.000 description 4
- 230000004044 response Effects 0.000 description 4
- 239000007787 solid Substances 0.000 description 4
- 239000003981 vehicle Substances 0.000 description 4
- 102000004506 Blood Proteins Human genes 0.000 description 3
- 108010017384 Blood Proteins Proteins 0.000 description 3
- SHZGCJCMOBCMKK-UHFFFAOYSA-N D-mannomethylose Natural products CC1OC(O)C(O)C(O)C1O SHZGCJCMOBCMKK-UHFFFAOYSA-N 0.000 description 3
- 108010020195 FLAG peptide Proteins 0.000 description 3
- 108010093488 His-His-His-His-His-His Proteins 0.000 description 3
- 108010073807 IgG Receptors Proteins 0.000 description 3
- 102000009490 IgG Receptors Human genes 0.000 description 3
- 102000008394 Immunoglobulin Fragments Human genes 0.000 description 3
- 108010021625 Immunoglobulin Fragments Proteins 0.000 description 3
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 3
- 241000282567 Macaca fascicularis Species 0.000 description 3
- 241000699670 Mus sp. Species 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 3
- 239000004480 active ingredient Substances 0.000 description 3
- 238000013459 approach Methods 0.000 description 3
- 239000011324 bead Substances 0.000 description 3
- 230000015861 cell surface binding Effects 0.000 description 3
- 230000008859 change Effects 0.000 description 3
- 238000004587 chromatography analysis Methods 0.000 description 3
- 238000004440 column chromatography Methods 0.000 description 3
- 238000012258 culturing Methods 0.000 description 3
- 239000003085 diluting agent Substances 0.000 description 3
- 239000003937 drug carrier Substances 0.000 description 3
- 230000009881 electrostatic interaction Effects 0.000 description 3
- 238000009472 formulation Methods 0.000 description 3
- 230000002068 genetic effect Effects 0.000 description 3
- 230000013595 glycosylation Effects 0.000 description 3
- 238000006206 glycosylation reaction Methods 0.000 description 3
- 230000001900 immune effect Effects 0.000 description 3
- 238000001802 infusion Methods 0.000 description 3
- 238000003780 insertion Methods 0.000 description 3
- 230000037431 insertion Effects 0.000 description 3
- 239000011159 matrix material Substances 0.000 description 3
- 108010068617 neonatal Fc receptor Proteins 0.000 description 3
- 210000005259 peripheral blood Anatomy 0.000 description 3
- 239000011886 peripheral blood Substances 0.000 description 3
- 239000000546 pharmaceutical excipient Substances 0.000 description 3
- 239000000825 pharmaceutical preparation Substances 0.000 description 3
- 102000040430 polynucleotide Human genes 0.000 description 3
- 108091033319 polynucleotide Proteins 0.000 description 3
- 239000002157 polynucleotide Substances 0.000 description 3
- 230000008569 process Effects 0.000 description 3
- 238000012545 processing Methods 0.000 description 3
- 239000004405 propyl p-hydroxybenzoate Substances 0.000 description 3
- 239000011347 resin Substances 0.000 description 3
- 229920005989 resin Polymers 0.000 description 3
- 125000003607 serino group Chemical group [H]N([H])[C@]([H])(C(=O)[*])C(O[H])([H])[H] 0.000 description 3
- 238000007920 subcutaneous administration Methods 0.000 description 3
- 238000012360 testing method Methods 0.000 description 3
- MTCFGRXMJLQNBG-REOHCLBHSA-N (2S)-2-Amino-3-hydroxypropansäure Chemical compound OC[C@H](N)C(O)=O MTCFGRXMJLQNBG-REOHCLBHSA-N 0.000 description 2
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 2
- 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 description 2
- 102100021266 Alpha-(1,6)-fucosyltransferase Human genes 0.000 description 2
- 102100022002 CD59 glycoprotein Human genes 0.000 description 2
- 101100454808 Caenorhabditis elegans lgg-2 gene Proteins 0.000 description 2
- 102100025680 Complement decay-accelerating factor Human genes 0.000 description 2
- WQZGKKKJIJFFOK-QTVWNMPRSA-N D-mannopyranose Chemical compound OC[C@H]1OC(O)[C@@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-QTVWNMPRSA-N 0.000 description 2
- 102100037362 Fibronectin Human genes 0.000 description 2
- 108010067306 Fibronectins Proteins 0.000 description 2
- PNNNRSAQSRJVSB-SLPGGIOYSA-N Fucose Natural products C[C@H](O)[C@@H](O)[C@H](O)[C@H](O)C=O PNNNRSAQSRJVSB-SLPGGIOYSA-N 0.000 description 2
- 101000819490 Homo sapiens Alpha-(1,6)-fucosyltransferase Proteins 0.000 description 2
- 101000897400 Homo sapiens CD59 glycoprotein Proteins 0.000 description 2
- 101000856022 Homo sapiens Complement decay-accelerating factor Proteins 0.000 description 2
- 101000917839 Homo sapiens Low affinity immunoglobulin gamma Fc region receptor III-B Proteins 0.000 description 2
- 102100029185 Low affinity immunoglobulin gamma Fc region receptor III-B Human genes 0.000 description 2
- 239000005089 Luciferase Substances 0.000 description 2
- 108091007491 NSP3 Papain-like protease domains Proteins 0.000 description 2
- 108091028043 Nucleic acid sequence Proteins 0.000 description 2
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 2
- 102000007562 Serum Albumin Human genes 0.000 description 2
- 108010071390 Serum Albumin Proteins 0.000 description 2
- 230000002776 aggregation Effects 0.000 description 2
- 238000004220 aggregation Methods 0.000 description 2
- 230000004075 alteration Effects 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- PYMYPHUHKUWMLA-UHFFFAOYSA-N arabinose Natural products OCC(O)C(O)C(O)C=O PYMYPHUHKUWMLA-UHFFFAOYSA-N 0.000 description 2
- 230000001580 bacterial effect Effects 0.000 description 2
- SRBFZHDQGSBBOR-UHFFFAOYSA-N beta-D-Pyranose-Lyxose Natural products OC1COC(O)C(O)C1O SRBFZHDQGSBBOR-UHFFFAOYSA-N 0.000 description 2
- 102000023732 binding proteins Human genes 0.000 description 2
- 108091008324 binding proteins Proteins 0.000 description 2
- 238000001574 biopsy Methods 0.000 description 2
- 239000001506 calcium phosphate Substances 0.000 description 2
- 229910000389 calcium phosphate Inorganic materials 0.000 description 2
- 235000011010 calcium phosphates Nutrition 0.000 description 2
- 239000006285 cell suspension Substances 0.000 description 2
- 239000012094 cell viability reagent Substances 0.000 description 2
- 230000001413 cellular effect Effects 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- 210000004978 chinese hamster ovary cell Anatomy 0.000 description 2
- 230000009827 complement-dependent cellular cytotoxicity Effects 0.000 description 2
- 239000000470 constituent Substances 0.000 description 2
- 238000007796 conventional method Methods 0.000 description 2
- 230000001461 cytolytic effect Effects 0.000 description 2
- 229940094732 darzalex Drugs 0.000 description 2
- 238000001514 detection method Methods 0.000 description 2
- 239000010432 diamond Substances 0.000 description 2
- 230000000447 dimerizing effect Effects 0.000 description 2
- 238000004520 electroporation Methods 0.000 description 2
- 238000005516 engineering process Methods 0.000 description 2
- 230000002708 enhancing effect Effects 0.000 description 2
- 239000013604 expression vector Substances 0.000 description 2
- 150000004676 glycans Chemical class 0.000 description 2
- 239000001963 growth medium Substances 0.000 description 2
- 230000036541 health Effects 0.000 description 2
- 239000000710 homodimer Substances 0.000 description 2
- 238000002868 homogeneous time resolved fluorescence Methods 0.000 description 2
- 238000003384 imaging method Methods 0.000 description 2
- 230000001976 improved effect Effects 0.000 description 2
- 238000000338 in vitro Methods 0.000 description 2
- 238000002955 isolation Methods 0.000 description 2
- 238000010859 live-cell imaging Methods 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 238000000520 microinjection Methods 0.000 description 2
- 210000001616 monocyte Anatomy 0.000 description 2
- 201000000050 myeloid neoplasm Diseases 0.000 description 2
- 210000000822 natural killer cell Anatomy 0.000 description 2
- 210000003463 organelle Anatomy 0.000 description 2
- 210000003819 peripheral blood mononuclear cell Anatomy 0.000 description 2
- 230000003285 pharmacodynamic effect Effects 0.000 description 2
- 239000002504 physiological saline solution Substances 0.000 description 2
- 230000004481 post-translational protein modification Effects 0.000 description 2
- 238000001556 precipitation Methods 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- 230000001737 promoting effect Effects 0.000 description 2
- 230000017854 proteolysis Effects 0.000 description 2
- 230000002829 reductive effect Effects 0.000 description 2
- 230000009834 selective interaction Effects 0.000 description 2
- 239000011780 sodium chloride Substances 0.000 description 2
- 239000004320 sodium erythorbate Substances 0.000 description 2
- 238000010254 subcutaneous injection Methods 0.000 description 2
- 239000007929 subcutaneous injection Substances 0.000 description 2
- 229920001059 synthetic polymer Polymers 0.000 description 2
- 238000001890 transfection Methods 0.000 description 2
- 230000009466 transformation Effects 0.000 description 2
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 2
- 239000013598 vector Substances 0.000 description 2
- 239000008215 water for injection Substances 0.000 description 2
- 101001084702 Arabidopsis thaliana Histone H2B.10 Proteins 0.000 description 1
- 239000004475 Arginine Substances 0.000 description 1
- 102100022005 B-lymphocyte antigen CD20 Human genes 0.000 description 1
- 102100024775 Beta-1,4-mannosyl-glycoprotein 4-beta-N-acetylglucosaminyltransferase Human genes 0.000 description 1
- 108030001771 Beta-1,4-mannosyl-glycoprotein 4-beta-N-acetylglucosaminyltransferases Proteins 0.000 description 1
- 108010069112 Complement System Proteins Proteins 0.000 description 1
- 102000000989 Complement System Proteins Human genes 0.000 description 1
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 1
- IGXWBGJHJZYPQS-SSDOTTSWSA-N D-Luciferin Chemical compound OC(=O)[C@H]1CSC(C=2SC3=CC=C(O)C=C3N=2)=N1 IGXWBGJHJZYPQS-SSDOTTSWSA-N 0.000 description 1
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 1
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 1
- 102000016928 DNA-directed DNA polymerase Human genes 0.000 description 1
- 108010014303 DNA-directed DNA polymerase Proteins 0.000 description 1
- CYCGRDQQIOGCKX-UHFFFAOYSA-N Dehydro-luciferin Natural products OC(=O)C1=CSC(C=2SC3=CC(O)=CC=C3N=2)=N1 CYCGRDQQIOGCKX-UHFFFAOYSA-N 0.000 description 1
- 238000002965 ELISA Methods 0.000 description 1
- 102000002090 Fibronectin type III Human genes 0.000 description 1
- 108050009401 Fibronectin type III Proteins 0.000 description 1
- BJGNCJDXODQBOB-UHFFFAOYSA-N Fivefly Luciferin Natural products OC(=O)C1CSC(C=2SC3=CC(O)=CC=C3N=2)=N1 BJGNCJDXODQBOB-UHFFFAOYSA-N 0.000 description 1
- 238000012413 Fluorescence activated cell sorting analysis Methods 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 1
- 101710154606 Hemagglutinin Proteins 0.000 description 1
- 241000238631 Hexapoda Species 0.000 description 1
- 101000897405 Homo sapiens B-lymphocyte antigen CD20 Proteins 0.000 description 1
- QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 description 1
- ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 description 1
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 1
- HNDVDQJCIGZPNO-YFKPBYRVSA-N L-histidine Chemical compound OC(=O)[C@@H](N)CC1=CN=CN1 HNDVDQJCIGZPNO-YFKPBYRVSA-N 0.000 description 1
- ROHFNLRQFUQHCH-YFKPBYRVSA-N L-leucine Chemical compound CC(C)C[C@H](N)C(O)=O ROHFNLRQFUQHCH-YFKPBYRVSA-N 0.000 description 1
- KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 description 1
- AYFVYJQAPQTCCC-GBXIJSLDSA-N L-threonine Chemical compound C[C@@H](O)[C@H](N)C(O)=O AYFVYJQAPQTCCC-GBXIJSLDSA-N 0.000 description 1
- QIVBCDIJIAJPQS-VIFPVBQESA-N L-tryptophane Chemical compound C1=CC=C2C(C[C@H](N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-VIFPVBQESA-N 0.000 description 1
- OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 description 1
- KZSNJWFQEVHDMF-BYPYZUCNSA-N L-valine Chemical compound CC(C)[C@H](N)C(O)=O KZSNJWFQEVHDMF-BYPYZUCNSA-N 0.000 description 1
- ROHFNLRQFUQHCH-UHFFFAOYSA-N Leucine Natural products CC(C)CC(N)C(O)=O ROHFNLRQFUQHCH-UHFFFAOYSA-N 0.000 description 1
- 108060001084 Luciferase Proteins 0.000 description 1
- DDWFXDSYGUXRAY-UHFFFAOYSA-N Luciferin Natural products CCc1c(C)c(CC2NC(=O)C(=C2C=C)C)[nH]c1Cc3[nH]c4C(=C5/NC(CC(=O)O)C(C)C5CC(=O)O)CC(=O)c4c3C DDWFXDSYGUXRAY-UHFFFAOYSA-N 0.000 description 1
- 108010046938 Macrophage Colony-Stimulating Factor Proteins 0.000 description 1
- 102100028123 Macrophage colony-stimulating factor 1 Human genes 0.000 description 1
- 241001529936 Murinae Species 0.000 description 1
- 241000699666 Mus <mouse, genus> Species 0.000 description 1
- 230000004988 N-glycosylation Effects 0.000 description 1
- 238000011887 Necropsy Methods 0.000 description 1
- 108091034117 Oligonucleotide Proteins 0.000 description 1
- 101710093908 Outer capsid protein VP4 Proteins 0.000 description 1
- 101710135467 Outer capsid protein sigma-1 Proteins 0.000 description 1
- 102000057297 Pepsin A Human genes 0.000 description 1
- 108090000284 Pepsin A Proteins 0.000 description 1
- 108091005804 Peptidases Proteins 0.000 description 1
- 239000004365 Protease Substances 0.000 description 1
- 101710176177 Protein A56 Proteins 0.000 description 1
- 108091030071 RNAI Proteins 0.000 description 1
- 102100037486 Reverse transcriptase/ribonuclease H Human genes 0.000 description 1
- 238000011579 SCID mouse model Methods 0.000 description 1
- 108091027967 Small hairpin RNA Proteins 0.000 description 1
- 108020004459 Small interfering RNA Proteins 0.000 description 1
- 102220497176 Small vasohibin-binding protein_T47D_mutation Human genes 0.000 description 1
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 1
- 230000006044 T cell activation Effects 0.000 description 1
- AYFVYJQAPQTCCC-UHFFFAOYSA-N Threonine Natural products CC(O)C(N)C(O)=O AYFVYJQAPQTCCC-UHFFFAOYSA-N 0.000 description 1
- 239000004473 Threonine Substances 0.000 description 1
- 101710120037 Toxin CcdB Proteins 0.000 description 1
- 102100023935 Transmembrane glycoprotein NMB Human genes 0.000 description 1
- QIVBCDIJIAJPQS-UHFFFAOYSA-N Tryptophan Natural products C1=CC=C2C(CC(N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-UHFFFAOYSA-N 0.000 description 1
- KZSNJWFQEVHDMF-UHFFFAOYSA-N Valine Natural products CC(C)C(N)C(O)=O KZSNJWFQEVHDMF-UHFFFAOYSA-N 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 238000001042 affinity chromatography Methods 0.000 description 1
- 235000004279 alanine Nutrition 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 125000003277 amino group Chemical group 0.000 description 1
- 230000000692 anti-sense effect Effects 0.000 description 1
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 1
- 235000003704 aspartic acid Nutrition 0.000 description 1
- 230000000712 assembly Effects 0.000 description 1
- 238000000429 assembly Methods 0.000 description 1
- 239000005441 aurora Substances 0.000 description 1
- 150000001540 azides Chemical class 0.000 description 1
- OQFSQFPPLPISGP-UHFFFAOYSA-N beta-carboxyaspartic acid Natural products OC(=O)C(N)C(C(O)=O)C(O)=O OQFSQFPPLPISGP-UHFFFAOYSA-N 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 230000008827 biological function Effects 0.000 description 1
- 239000008366 buffered solution Substances 0.000 description 1
- 238000004364 calculation method Methods 0.000 description 1
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 1
- 125000002843 carboxylic acid group Chemical group 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 239000013592 cell lysate Substances 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- 238000006482 condensation reaction Methods 0.000 description 1
- 235000018417 cysteine Nutrition 0.000 description 1
- SSJJWVREPZVNBF-DGXVIIAXSA-N dG10 Chemical compound C1=NC(C(NC(N)=N2)=O)=C2N1[C@H](O[C@@H]1COP(O)(=O)O[C@@H]2[C@H](O[C@H](C2)N2C3=C(C(NC(N)=N3)=O)N=C2)COP(O)(=O)O[C@@H]2[C@H](O[C@H](C2)N2C3=C(C(NC(N)=N3)=O)N=C2)COP(O)(=O)O[C@@H]2[C@H](O[C@H](C2)N2C3=C(C(NC(N)=N3)=O)N=C2)COP(O)(=O)O[C@@H]2[C@H](O[C@H](C2)N2C3=C(C(NC(N)=N3)=O)N=C2)COP(O)(=O)O[C@@H]2[C@H](O[C@H](C2)N2C3=C(C(NC(N)=N3)=O)N=C2)COP(O)(=O)O[C@@H]2[C@H](O[C@H](C2)N2C3=C(C(NC(N)=N3)=O)N=C2)COP(O)(=O)O[C@@H]2[C@H](O[C@H](C2)N2C3=C(C(NC(N)=N3)=O)N=C2)COP(O)(=O)O[C@@H]2[C@H](O[C@H](C2)N2C3=C(C(NC(N)=N3)=O)N=C2)CO)C[C@@H]1OP(O)(=O)OC[C@@H](O1)[C@@H](O)C[C@@H]1N1C(N=C(NC2=O)N)=C2N=C1 SSJJWVREPZVNBF-DGXVIIAXSA-N 0.000 description 1
- 239000007857 degradation product Substances 0.000 description 1
- 238000006731 degradation reaction Methods 0.000 description 1
- 230000002939 deleterious effect Effects 0.000 description 1
- 238000000502 dialysis Methods 0.000 description 1
- 239000012153 distilled water Substances 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 239000003623 enhancer Substances 0.000 description 1
- 210000003743 erythrocyte Anatomy 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 210000003527 eukaryotic cell Anatomy 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 102000006815 folate receptor Human genes 0.000 description 1
- 230000033581 fucosylation Effects 0.000 description 1
- 230000002538 fungal effect Effects 0.000 description 1
- 230000004927 fusion Effects 0.000 description 1
- 229930182830 galactose Natural products 0.000 description 1
- 238000001502 gel electrophoresis Methods 0.000 description 1
- 230000009368 gene silencing by RNA Effects 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 235000013922 glutamic acid Nutrition 0.000 description 1
- 239000004220 glutamic acid Substances 0.000 description 1
- 230000012010 growth Effects 0.000 description 1
- 239000000185 hemagglutinin Substances 0.000 description 1
- 208000019691 hematopoietic and lymphoid cell neoplasm Diseases 0.000 description 1
- 208000024200 hematopoietic and lymphoid system neoplasm Diseases 0.000 description 1
- HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 230000002209 hydrophobic effect Effects 0.000 description 1
- 230000005934 immune activation Effects 0.000 description 1
- 208000026278 immune system disease Diseases 0.000 description 1
- 238000003018 immunoassay Methods 0.000 description 1
- 238000002513 implantation Methods 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 230000001965 increasing effect Effects 0.000 description 1
- 230000001939 inductive effect Effects 0.000 description 1
- 208000027866 inflammatory disease Diseases 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 239000007972 injectable composition Substances 0.000 description 1
- 210000005007 innate immune system Anatomy 0.000 description 1
- 238000005342 ion exchange Methods 0.000 description 1
- 239000000644 isotonic solution Substances 0.000 description 1
- 230000002147 killing effect Effects 0.000 description 1
- 210000000265 leukocyte Anatomy 0.000 description 1
- 239000003446 ligand Substances 0.000 description 1
- 230000000670 limiting effect Effects 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 238000004020 luminiscence type Methods 0.000 description 1
- 210000004698 lymphocyte Anatomy 0.000 description 1
- 230000014759 maintenance of location Effects 0.000 description 1
- 230000003211 malignant effect Effects 0.000 description 1
- 210000004962 mammalian cell Anatomy 0.000 description 1
- 239000003550 marker Substances 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 108091070501 miRNA Proteins 0.000 description 1
- 239000002679 microRNA Substances 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 238000010369 molecular cloning Methods 0.000 description 1
- 210000005087 mononuclear cell Anatomy 0.000 description 1
- 238000002703 mutagenesis Methods 0.000 description 1
- 231100000350 mutagenesis Toxicity 0.000 description 1
- 210000000066 myeloid cell Anatomy 0.000 description 1
- 239000002736 nonionic surfactant Substances 0.000 description 1
- 229940111202 pepsin Drugs 0.000 description 1
- 230000003094 perturbing effect Effects 0.000 description 1
- 229940127557 pharmaceutical product Drugs 0.000 description 1
- 239000002953 phosphate buffered saline Substances 0.000 description 1
- 210000003720 plasmablast Anatomy 0.000 description 1
- 239000013612 plasmid Substances 0.000 description 1
- 230000008488 polyadenylation Effects 0.000 description 1
- 229950008882 polysorbate Drugs 0.000 description 1
- 229920000136 polysorbate Polymers 0.000 description 1
- 230000001323 posttranslational effect Effects 0.000 description 1
- 230000036515 potency Effects 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 210000001236 prokaryotic cell Anatomy 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- 230000009145 protein modification Effects 0.000 description 1
- 238000001742 protein purification Methods 0.000 description 1
- 230000005180 public health Effects 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 238000012552 review Methods 0.000 description 1
- 238000005185 salting out Methods 0.000 description 1
- 230000028327 secretion Effects 0.000 description 1
- 230000035945 sensitivity Effects 0.000 description 1
- 125000005629 sialic acid group Chemical group 0.000 description 1
- 230000009450 sialylation Effects 0.000 description 1
- 239000002924 silencing RNA Substances 0.000 description 1
- 238000001542 size-exclusion chromatography Methods 0.000 description 1
- 239000004055 small Interfering RNA Substances 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 229960002920 sorbitol Drugs 0.000 description 1
- 210000000952 spleen Anatomy 0.000 description 1
- 230000002269 spontaneous effect Effects 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 239000008174 sterile solution Substances 0.000 description 1
- 239000008227 sterile water for injection Substances 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 150000005846 sugar alcohols Polymers 0.000 description 1
- 239000013589 supplement Substances 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 239000000375 suspending agent Substances 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 230000008685 targeting Effects 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 238000013518 transcription Methods 0.000 description 1
- 230000035897 transcription Effects 0.000 description 1
- 230000014616 translation Effects 0.000 description 1
- 108091007466 transmembrane glycoproteins Proteins 0.000 description 1
- 238000012384 transportation and delivery Methods 0.000 description 1
- 230000004614 tumor growth Effects 0.000 description 1
- 230000005909 tumor killing Effects 0.000 description 1
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 1
- 238000000108 ultra-filtration Methods 0.000 description 1
- 239000004474 valine Substances 0.000 description 1
- 239000011800 void material Substances 0.000 description 1
- 230000003442 weekly effect Effects 0.000 description 1
- 238000001262 western blot Methods 0.000 description 1
- 239000012130 whole-cell lysate Substances 0.000 description 1
Classifications
-
- 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
- C07K16/28—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
- C07K16/2896—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against molecules with a "CD"-designation, not provided for elsewhere
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A61P35/02—Antineoplastic agents specific for leukemia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K2039/505—Medicinal preparations containing antigens or antibodies comprising antibodies
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
- C07K2317/52—Constant or Fc region; Isotype
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
- C07K2317/55—Fab or Fab'
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/60—Immunoglobulins specific features characterized by non-natural combinations of immunoglobulin fragments
- C07K2317/64—Immunoglobulins specific features characterized by non-natural combinations of immunoglobulin fragments comprising a combination of variable region and constant region components
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/70—Immunoglobulins specific features characterized by effect upon binding to a cell or to an antigen
- C07K2317/72—Increased effector function due to an Fc-modification
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/70—Immunoglobulins specific features characterized by effect upon binding to a cell or to an antigen
- C07K2317/73—Inducing cell death, e.g. apoptosis, necrosis or inhibition of cell proliferation
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/70—Immunoglobulins specific features characterized by effect upon binding to a cell or to an antigen
- C07K2317/73—Inducing cell death, e.g. apoptosis, necrosis or inhibition of cell proliferation
- C07K2317/732—Antibody-dependent cellular cytotoxicity [ADCC]
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/70—Immunoglobulins specific features characterized by effect upon binding to a cell or to an antigen
- C07K2317/73—Inducing cell death, e.g. apoptosis, necrosis or inhibition of cell proliferation
- C07K2317/734—Complement-dependent cytotoxicity [CDC]
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Medicinal Chemistry (AREA)
- Immunology (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Molecular Biology (AREA)
- Biophysics (AREA)
- Biochemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Genetics & Genomics (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Hematology (AREA)
- Oncology (AREA)
- Peptides Or Proteins (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201962902380P | 2019-09-18 | 2019-09-18 | |
| US62/902,380 | 2019-09-18 | ||
| PCT/US2020/051663 WO2021055876A1 (en) | 2019-09-18 | 2020-09-18 | COMPOSITIONS AND METHODS RELATED TO ENGINEERED Fc-ANTIGEN BINDING DOMAIN CONSTRUCTS TARGETED TO CD38 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| AU2020351234A1 true AU2020351234A1 (en) | 2022-04-28 |
Family
ID=74884204
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| AU2020351234A Pending AU2020351234A1 (en) | 2019-09-18 | 2020-09-18 | Compositions and methods related to engineered Fc-antigen binding domain constructs targeted to CD38 |
Country Status (10)
| Country | Link |
|---|---|
| EP (1) | EP4031166A1 (es) |
| JP (1) | JP2022548925A (es) |
| KR (1) | KR20220119362A (es) |
| CN (1) | CN114786713A (es) |
| AU (1) | AU2020351234A1 (es) |
| BR (1) | BR112022005036A2 (es) |
| CA (1) | CA3155187A1 (es) |
| IL (1) | IL291465A (es) |
| MX (1) | MX2022003316A (es) |
| WO (1) | WO2021055876A1 (es) |
Family Cites Families (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| RS56677B1 (sr) * | 2005-10-12 | 2018-03-30 | Morphosys Ag | Proizvodnja i karakterizacija potpuno humanih terapeutskih antitela dobijenih hucal gold tehnologijom, specifičnih za humani cd38 |
| CN110317272A (zh) * | 2008-10-14 | 2019-10-11 | 霍夫曼-拉罗奇有限公司 | 免疫球蛋白变体及其用途 |
| DK3105317T3 (en) * | 2014-02-14 | 2019-01-14 | Cellectis | Immunotherapy cells that are genetically engineered to target antigen on both immune cells and pathological cells |
| WO2015197582A1 (en) * | 2014-06-27 | 2015-12-30 | Innate Pharma | Monomeric multispecific antigen binding proteins |
| US20200040084A1 (en) * | 2017-01-06 | 2020-02-06 | Momenta Pharmaceuticals, Inc. | Compositions and methods related to engineered fc-antigen binding domain constructs |
-
2020
- 2020-09-18 KR KR1020227012833A patent/KR20220119362A/ko unknown
- 2020-09-18 CN CN202080080169.6A patent/CN114786713A/zh active Pending
- 2020-09-18 BR BR112022005036A patent/BR112022005036A2/pt not_active Application Discontinuation
- 2020-09-18 AU AU2020351234A patent/AU2020351234A1/en active Pending
- 2020-09-18 EP EP20864518.4A patent/EP4031166A1/en active Pending
- 2020-09-18 JP JP2022517471A patent/JP2022548925A/ja active Pending
- 2020-09-18 CA CA3155187A patent/CA3155187A1/en active Pending
- 2020-09-18 WO PCT/US2020/051663 patent/WO2021055876A1/en unknown
- 2020-09-18 MX MX2022003316A patent/MX2022003316A/es unknown
-
2022
- 2022-03-17 IL IL291465A patent/IL291465A/en unknown
Also Published As
| Publication number | Publication date |
|---|---|
| JP2022548925A (ja) | 2022-11-22 |
| KR20220119362A (ko) | 2022-08-29 |
| IL291465A (en) | 2022-05-01 |
| EP4031166A1 (en) | 2022-07-27 |
| MX2022003316A (es) | 2022-07-11 |
| BR112022005036A2 (pt) | 2022-07-05 |
| CA3155187A1 (en) | 2021-03-25 |
| WO2021055876A1 (en) | 2021-03-25 |
| CN114786713A (zh) | 2022-07-22 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US20200040084A1 (en) | Compositions and methods related to engineered fc-antigen binding domain constructs | |
| US20210269546A1 (en) | COMPOSITIONS AND METHODS RELATED TO ENGINEERED Fc-ANTIGEN BINDING DOMAIN CONSTRUCTS TARGETED TO CD38 | |
| US20210317227A1 (en) | COMPOSITIONS AND METHODS RELATED TO ENGINEERED Fc-ANTIGEN BINDING DOMAIN CONSTRUCTS | |
| US20220267460A1 (en) | COMPOSITIONS AND METHODS RELATED TO ENGINEERED Fc-ANTIGEN BINDING DOMAIN CONSTRUCTS | |
| EP3820521A2 (en) | Compositions and methods related to engineered fc-antigen binding domain constructs targeted to ctla-4 | |
| EP3820517A2 (en) | Compositions and methods related to engineered fc-antigen binding domain constructs targeted to ccr4 | |
| WO2021055876A1 (en) | COMPOSITIONS AND METHODS RELATED TO ENGINEERED Fc-ANTIGEN BINDING DOMAIN CONSTRUCTS TARGETED TO CD38 | |
| AU2019300020A1 (en) | Compositions and methods related to engineered Fc-antigen binding domain constructs | |
| US20210147549A1 (en) | COMPOSITIONS AND METHODS RELATED TO ENGINEERED Fc-ANTIGEN BINDING DOMAIN CONSTRUCTS TARGETED TO PD-L1 |