CA3049426A1 - Compositions and methods related to engineered fc-antigen binding domain constructs - Google Patents
Compositions and methods related to engineered fc-antigen binding domain constructs Download PDFInfo
- Publication number
- CA3049426A1 CA3049426A1 CA3049426A CA3049426A CA3049426A1 CA 3049426 A1 CA3049426 A1 CA 3049426A1 CA 3049426 A CA3049426 A CA 3049426A CA 3049426 A CA3049426 A CA 3049426A CA 3049426 A1 CA3049426 A1 CA 3049426A1
- Authority
- CA
- Canada
- Prior art keywords
- domain
- polypeptide
- domain monomer
- monomer
- antigen binding
- 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.)
- Abandoned
Links
- 239000000427 antigen Substances 0.000 title claims abstract description 575
- 239000000203 mixture Substances 0.000 title claims abstract description 25
- 238000000034 method Methods 0.000 title claims abstract description 18
- 102000036639 antigens Human genes 0.000 claims abstract description 316
- 108091007433 antigens Proteins 0.000 claims abstract description 316
- 239000000178 monomer Substances 0.000 claims description 1890
- 108090000765 processed proteins & peptides Proteins 0.000 claims description 988
- 229920001184 polypeptide Polymers 0.000 claims description 983
- 102000004196 processed proteins & peptides Human genes 0.000 claims description 983
- 230000035772 mutation Effects 0.000 claims description 246
- 235000001014 amino acid Nutrition 0.000 claims description 229
- 125000003275 alpha amino acid group Chemical group 0.000 claims description 202
- 150000001413 amino acids Chemical class 0.000 claims description 162
- 238000006471 dimerization reaction Methods 0.000 claims description 146
- 238000005304 joining Methods 0.000 claims description 132
- 230000002441 reversible effect Effects 0.000 claims description 127
- 238000006467 substitution reaction Methods 0.000 claims description 81
- 230000000295 complement effect Effects 0.000 claims description 70
- 125000006850 spacer group Chemical group 0.000 claims description 64
- NFGXHKASABOEEW-UHFFFAOYSA-N 1-methylethyl 11-methoxy-3,7,11-trimethyl-2,4-dodecadienoate Chemical group COC(C)(C)CCCC(C)CC=CC(C)=CC(=O)OC(C)C NFGXHKASABOEEW-UHFFFAOYSA-N 0.000 claims description 61
- 230000004048 modification Effects 0.000 claims description 41
- 238000012986 modification Methods 0.000 claims description 41
- 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 claims description 36
- 108010044804 gamma-glutamyl-seryl-glycine Proteins 0.000 claims description 36
- 230000005888 antibody-dependent cellular phagocytosis Effects 0.000 claims description 33
- 230000004540 complement-dependent cytotoxicity Effects 0.000 claims description 33
- 238000003556 assay Methods 0.000 claims description 26
- 238000004113 cell culture Methods 0.000 claims description 24
- 239000012228 culture supernatant Substances 0.000 claims description 24
- 125000003630 glycyl group Chemical group [H]N([H])C([H])([H])C(*)=O 0.000 claims description 24
- 210000004027 cell Anatomy 0.000 claims description 23
- 239000012636 effector Substances 0.000 claims description 20
- 239000006143 cell culture medium Substances 0.000 claims description 18
- 230000004071 biological effect Effects 0.000 claims description 17
- 230000003013 cytotoxicity Effects 0.000 claims description 14
- 231100000135 cytotoxicity Toxicity 0.000 claims description 14
- 238000012217 deletion Methods 0.000 claims description 14
- 230000037430 deletion Effects 0.000 claims description 14
- 230000001419 dependent effect Effects 0.000 claims description 14
- 238000012258 culturing Methods 0.000 claims description 13
- 238000004519 manufacturing process Methods 0.000 claims description 12
- 150000007523 nucleic acids Chemical class 0.000 claims description 12
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Natural products NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 claims description 11
- 239000004471 Glycine Substances 0.000 claims description 11
- 102000039446 nucleic acids Human genes 0.000 claims description 11
- 108020004707 nucleic acids Proteins 0.000 claims description 11
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 claims description 10
- 239000004472 Lysine Substances 0.000 claims description 10
- 210000004899 c-terminal region Anatomy 0.000 claims description 10
- 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 claims description 10
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 10
- 125000000151 cysteine group Chemical group N[C@@H](CS)C(=O)* 0.000 claims description 8
- 230000000694 effects Effects 0.000 claims description 6
- 102100027211 Albumin Human genes 0.000 claims description 5
- 108010088751 Albumins Proteins 0.000 claims description 5
- 230000015572 biosynthetic process Effects 0.000 claims description 5
- 239000008194 pharmaceutical composition Substances 0.000 claims description 5
- 239000001963 growth medium Substances 0.000 claims description 4
- 108010087819 Fc receptors Proteins 0.000 claims description 3
- 102000009109 Fc receptors Human genes 0.000 claims description 3
- 239000013604 expression vector Substances 0.000 claims description 3
- 230000001404 mediated effect Effects 0.000 claims description 3
- 101100454807 Caenorhabditis elegans lgg-1 gene Proteins 0.000 claims 53
- 101100217502 Caenorhabditis elegans lgg-3 gene Proteins 0.000 claims 1
- SHZGCJCMOBCMKK-UHFFFAOYSA-N D-mannomethylose Natural products CC1OC(O)C(O)C(O)C1O SHZGCJCMOBCMKK-UHFFFAOYSA-N 0.000 claims 1
- 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 claims 1
- 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 claims 1
- 230000010056 antibody-dependent cellular cytotoxicity Effects 0.000 description 12
- 230000006870 function Effects 0.000 description 12
- 230000001225 therapeutic effect Effects 0.000 description 6
- 239000004405 propyl p-hydroxybenzoate Substances 0.000 description 2
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 230000033581 fucosylation Effects 0.000 description 1
- 238000005734 heterodimerization reaction Methods 0.000 description 1
- 210000005007 innate immune system Anatomy 0.000 description 1
- 235000018102 proteins Nutrition 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 230000002829 reductive effect Effects 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
- C07K16/2887—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against CD20
-
- 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
- C07K16/2803—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against the immunoglobulin superfamily
- C07K16/2827—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against the immunoglobulin superfamily against B7 molecules, e.g. CD80, CD86
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/30—Immunoglobulins specific features characterized by aspects of specificity or valency
- C07K2317/35—Valency
-
- 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
- C07K2317/52—Constant or Fc region; Isotype
- C07K2317/524—CH2 domain
-
- 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
- C07K2317/526—CH3 domain
-
- 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
- C07K2317/53—Hinge
-
- 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
- C07K2317/50—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
- C07K2317/60—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
- 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]
-
- 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
Landscapes
- Health & Medical Sciences (AREA)
- Immunology (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Medicinal Chemistry (AREA)
- Biophysics (AREA)
- General Health & Medical Sciences (AREA)
- Genetics & Genomics (AREA)
- Biochemistry (AREA)
- Molecular Biology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Life Sciences & Earth Sciences (AREA)
- Peptides Or Proteins (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Medicinal Preparation (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201762443523P | 2017-01-06 | 2017-01-06 | |
| US62/443,523 | 2017-01-06 | ||
| PCT/US2018/012689 WO2018129397A1 (en) | 2017-01-06 | 2018-01-05 | Compositions and methods related to engineered fc-antigen binding domain constructs |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA3049426A1 true CA3049426A1 (en) | 2018-07-12 |
Family
ID=62791385
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA3049426A Abandoned CA3049426A1 (en) | 2017-01-06 | 2018-01-05 | Compositions and methods related to engineered fc-antigen binding domain constructs |
Country Status (7)
| Country | Link |
|---|---|
| US (1) | US20200040084A1 (enExample) |
| EP (1) | EP3565595A4 (enExample) |
| JP (1) | JP2020514301A (enExample) |
| AU (1) | AU2018205272A1 (enExample) |
| CA (1) | CA3049426A1 (enExample) |
| RU (1) | RU2019124709A (enExample) |
| WO (1) | WO2018129397A1 (enExample) |
Families Citing this family (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20210206857A1 (en) * | 2018-05-21 | 2021-07-08 | Bioprocessia Technologies Llc | Multivalent protein complexes |
| BR112021000392A2 (pt) * | 2018-07-11 | 2021-04-06 | Momenta Pharmaceuticals, Inc. | Composições e métodos relacionados a construtos do domínio de ligação fc-antígeno manipulados |
| AU2019300020A1 (en) * | 2018-07-11 | 2021-02-18 | Momenta Pharmaceuticals, Inc. | Compositions and methods related to engineered Fc-antigen binding domain constructs |
| EP3820910A4 (en) * | 2018-07-11 | 2022-06-22 | Momenta Pharmaceuticals, Inc. | COMPOSITIONS AND METHODS RELATING TO ENGINEERED FC ANTIGEN-BINDING DOMAIN CONSTRUCTS |
| BR112021000415A2 (pt) * | 2018-07-11 | 2021-04-06 | Momenta Pharmaceuticals, Inc. | Composições e métodos relacionados a construtos do domínio de ligação fc-antígeno manipulados |
| BR112021016829A2 (pt) | 2019-02-26 | 2021-10-19 | Pieris Pharmaceuticals Gmbh | Proteínas de fusão, molécula de ácido nucleico, métodos de produção, de ativar simultaneamente as vias de sinalização, de coestimular células t, de induzir uma resposta de linfócitos e de induzir o aumento da citólise, composição farmacêutica e método para prevenir, melhorar ou tratar cânceres |
| CN111909268B (zh) * | 2019-05-07 | 2022-04-19 | 北京天成新脉生物技术有限公司 | 低免疫原性低ADCC/CDC功能抗TNF-α人源化单克隆抗体TCX060及其应用 |
| EP4031166A1 (en) * | 2019-09-18 | 2022-07-27 | Momenta Pharmaceuticals, Inc. | Compositions and methods related to engineered fc-antigen binding domain constructs targeted to cd38 |
| KR20230060546A (ko) | 2021-10-22 | 2023-05-04 | 상트네어바이오사이언스 주식회사 | 두개의 Fc 도메인을 포함하는 항원 결합 단백질 및 이의 용도 |
| WO2024219897A1 (ko) | 2023-04-21 | 2024-10-24 | 상트네어바이오사이언스 주식회사 | 두 개의 fab 도메인 및 두 개의 fc 도메인을 포함하는 항원 결합 단백질 및 이의 용도 |
| WO2024219894A1 (ko) | 2023-04-21 | 2024-10-24 | 상트네어바이오사이언스 주식회사 | 두 개의 fc 도메인을 포함하는 항원 결합 단백질 및 이의 용도 |
Family Cites Families (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP5598894B2 (ja) * | 2006-03-03 | 2014-10-01 | 学校法人東京理科大学 | 生物活性を強化した抗体改変体 |
| CA2685698A1 (en) * | 2007-04-30 | 2008-11-13 | Centocor Ortho Biotech Inc. | Anti-tissue factor antibodies and compositions with enhanced effector function |
| BR112013019975A2 (pt) * | 2011-02-28 | 2017-08-01 | Hoffmann La Roche | proteínas de ligação de antígeno, composição farmacêutica, uso de uma proteína de ligação de antígeno, método para o tratamento de um paciente e método para a preparação de uma proteína de ligação de antígeno, ácido nucleico, vetor e célula hospedeira" |
| MX2014001019A (es) * | 2011-07-27 | 2014-05-13 | Glaxo Group Ltd | Dominios variables singulares anti-vgf fusionados con dominios de fc. |
| WO2014138449A1 (en) * | 2013-03-06 | 2014-09-12 | Merrimack Pharmaceuticals, Inc. | Anti-c-met tandem fc bispecific antibodies |
| US10858417B2 (en) * | 2013-03-15 | 2020-12-08 | Xencor, Inc. | Heterodimeric proteins |
| IL286367B2 (en) * | 2014-05-02 | 2023-03-01 | Momenta Pharmaceuticals Inc | Compositions and methods relating to engineered fc constructs |
-
2018
- 2018-01-05 US US16/474,572 patent/US20200040084A1/en not_active Abandoned
- 2018-01-05 RU RU2019124709A patent/RU2019124709A/ru unknown
- 2018-01-05 EP EP18735797.5A patent/EP3565595A4/en not_active Withdrawn
- 2018-01-05 AU AU2018205272A patent/AU2018205272A1/en not_active Abandoned
- 2018-01-05 CA CA3049426A patent/CA3049426A1/en not_active Abandoned
- 2018-01-05 WO PCT/US2018/012689 patent/WO2018129397A1/en not_active Ceased
- 2018-01-05 JP JP2019537110A patent/JP2020514301A/ja active Pending
Also Published As
| Publication number | Publication date |
|---|---|
| WO2018129397A1 (en) | 2018-07-12 |
| EP3565595A4 (en) | 2021-03-17 |
| US20200040084A1 (en) | 2020-02-06 |
| RU2019124709A3 (enExample) | 2021-12-21 |
| AU2018205272A1 (en) | 2019-07-25 |
| JP2020514301A (ja) | 2020-05-21 |
| RU2019124709A (ru) | 2021-02-08 |
| EP3565595A1 (en) | 2019-11-13 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| FZDE | Discontinued |
Effective date: 20240417 |